Arizona Advanced Medicine Clinic

Strengthening the GI Tract to Enhance Cognitive Health

July 2009
By CP Staff
CPlogo

At first glance, the intestinal tract and the brain seem like unlikely allies in the support of proper cognitive and emotional health. They are located at opposite ends of the body and seem to have widely different functions. Yet, emerging research indicates that both the gut and the brain play a beneficial role in cognitive health. New studies are showing that variations in gut microflora may be associated with changes in the normal functioning of the nervous system, a fact that is revealing new possibilities for probiotic bacteria in regards to brain health.

Normal gastrointestinal health relies on a properly functioning brain-gut axis, in which serotonin facilitates communication between the enteric nervous system (ENS) and the rest of the gut, driving functions such as gut motility and pain perception. Serotonin is a predominant signaling molecule in this process with up to 95 percent of the body’s serotonin found in the gut. Consequently, it’s not surprising that if the gastrointestinal system becomes upset, well being and cognitive health may suffer.

The gastrointestinal (GI) tract is a delicately balanced system in many ways and any breach in its natural defenses or normal function can create problems that extend beyond the gut to the brain and elsewhere. Research shows that defects in serotonin signaling can contribute to the pathophysiology of irritable bowel syndrome (IBS) and other gut motility disorders.[1]

In addition to serotonin, an optimal functioning GI tract requires a healthy population of naturally occurring probiotic (or friendly) bacteria, such as Lactobacilli and Bifidobacteria, which play a key role in preventing the overgrowth of harmful enterobacteria. An absence of probiotic bacteria has adverse effects not only locally in the gut but has also been shown to affect the central hypothalamus-pituitary-adrenal axis and monoaminergic activity, both of which have been implicated in the etiology of depression.[2] In a paper entitled, “Mood and gut feelings,” Canadian researchers present evidence that variations in the composition of gut microbes may be associated with changes in the normal functioning of the nervous system.[3]

If the delicate balance of the microflora environment is upset, toxic bacteria can out-compete health-promoting probiotic bacteria, causing not only gas and bloating, but also inflammation of the gut’s mucosal lining - a single layer of epithelial cells held together by tight junctions that provide a barrier between the GI tract and the bloodstream. Chronic inflammation of the mucosal lining increases total burden of absorbed foreign material, be it protein, microorganisms, or toxins. The release of unwanted material into the rest of the body in this way is referred to as the “leaky gut” syndrome and is an emerging factor in the development of a number of neuropsychological illnesses as highlighted below.

GI Diseases and the Cognitive Connection

Scientists began establishing a link between the gut and the brain during studies of irritable bowel syndrome and inflammatory bowel disease patients. Irritable bowel syndrome (IBS) is a debilitating intestinal disorder that affects up to 25 percent[4] of the American population and is one of the most common conditions seen in primary care settings.[5] It is characterized by intermittent abdominal pain, altered bowel habits, and other symptoms such as bloating that can have a profound impact on emotional health and quality of life.[6] Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine and includes such disorders as ulcerative colitis and Crohn’s disease.

A new study released in June of this year found that patients with inflammatory bowel disease have an increased incidence of verbal IQ deficit (a reduced ability to recall words). The researchers found evidence of a verbal IQ decrement in both IBD and IBS patients when measured against both healthy controls and against the patients’ own pre-disease IQ scores. The verbal IQ deficit was particularly pronounced in the inflammatory bowel disease patients.[7]

Furthermore, psychiatric disorders especially major depression and anxiety can be seen in up to 94 percent of IBS patients, and the disorder is frequently interconnected with fibromyalgia and chronic fatigue syndrome.[8] The treatments used for IBS patients often are tied as much to emotional health as to gut health. For example, cognitive-behavioral therapy is known to be effective in IBS sufferers.[9]

IBS sufferers demonstrate significantly lower concentrations of the probiotics Bifidobacteria and Lactobacilli compared with healthy controls.[11] While the etiology of IBS remains unclear, researchers believe both inflammatory changes[10] and modifications in the normal gut flora[6] play a role and that probiotics may favorably alter that milieu.

Depression

The role of the leaky gut syndrome in depression is supported by mounting research that has uncovered higher levels of serum antibodies against toxins from pathogenic enterobacteria in patients with depression compared with healthy controls.[12-15] In one study, researchers noted the differences to be so significant that the results could actually be used to diagnose depression with an accuracy rate of 90 percent.[14]

Chronic Fatigue Syndrome

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.[16] More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.[16] More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.[16] As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.[17] Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.[16]

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

In addition to serotonin, an optimal functioning GI tract requires a healthy population of naturally occurring probiotic (or friendly) bacteria, such as Lactobacilli and Bifidobacteria, which play a key role in preventing the overgrowth of harmful enterobacteria. An absence of probiotic bacteria has adverse effects not only locally in the gut but has also been shown to affect the central hypothalamus-pituitary-adrenal axis and monoaminergic activity, both of which have been implicated in the etiology of depression.[2] In a paper entitled, “Mood and gut feelings,” Canadian researchers present evidence that variations in the composition of gut microbes may be associated with changes in the normal functioning of the nervous system.[3]

If the delicate balance of the microflora environment is upset, toxic bacteria can out-compete health-promoting probiotic bacteria, causing not only gas and bloating, but also inflammation of the gut’s mucosal lining - a single layer of epithelial cells held together by tight junctions that provide a barrier between the GI tract and the bloodstream. Chronic inflammation of the mucosal lining increases total burden of absorbed foreign material, be it protein, microorganisms, or toxins. The release of unwanted material into the rest of the body in this way is referred to as the “leaky gut” syndrome and is an emerging factor in the development of a number of neuropsychological illnesses as highlighted below.

GI Diseases and the Cognitive Connection

Scientists began establishing a link between the gut and the brain during studies of irritable bowel syndrome and inflammatory bowel disease patients. Irritable bowel syndrome (IBS) is a debilitating intestinal disorder that affects up to 25 percent[4] of the American population and is one of the most common conditions seen in primary care settings.[5] It is characterized by intermittent abdominal pain, altered bowel habits, and other symptoms such as bloating that can have a profound impact on emotional health and quality of life.[6] Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine and includes such disorders as ulcerative colitis and Crohn’s disease.

A new study released in June of this year found that patients with inflammatory bowel disease have an increased incidence of verbal IQ deficit (a reduced ability to recall words). The researchers found evidence of a verbal IQ decrement in both IBD and IBS patients when measured against both healthy controls and against the patients’ own pre-disease IQ scores. The verbal IQ deficit was particularly pronounced in the inflammatory bowel disease patients.[7]

Furthermore, psychiatric disorders especially major depression and anxiety can be seen in up to 94 percent of IBS patients, and the disorder is frequently interconnected with fibromyalgia and chronic fatigue syndrome.[8] The treatments used for IBS patients often are tied as much to emotional health as to gut health. For example, cognitive-behavioral therapy is known to be effective in IBS sufferers.[9]

IBS sufferers demonstrate significantly lower concentrations of the probiotics Bifidobacteria and Lactobacilli compared with healthy controls.[11] While the etiology of IBS remains unclear, researchers believe both inflammatory changes[10] and modifications in the normal gut flora[6] play a role and that probiotics may favorably alter that milieu.

Depression

The role of the leaky gut syndrome in depression is supported by mounting research that has uncovered higher levels of serum antibodies against toxins from pathogenic enterobacteria in patients with depression compared with healthy controls.[12-15] In one study, researchers noted the differences to be so significant that the results could actually be used to diagnose depression with an accuracy rate of 90 percent.[14]

Chronic Fatigue Syndrome

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.[16] More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.[16] More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.[16] As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.[17] Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.[16]

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

If the delicate balance of the microflora environment is upset, toxic bacteria can out-compete health-promoting probiotic bacteria, causing not only gas and bloating, but also inflammation of the gut’s mucosal lining - a single layer of epithelial cells held together by tight junctions that provide a barrier between the GI tract and the bloodstream. Chronic inflammation of the mucosal lining increases total burden of absorbed foreign material, be it protein, microorganisms, or toxins. The release of unwanted material into the rest of the body in this way is referred to as the “leaky gut” syndrome and is an emerging factor in the development of a number of neuropsychological illnesses as highlighted below.

Scientists began establishing a link between the gut and the brain during studies of irritable bowel syndrome and inflammatory bowel disease patients. Irritable bowel syndrome (IBS) is a debilitating intestinal disorder that affects up to 25 percent[4] of the American population and is one of the most common conditions seen in primary care settings.[5] It is characterized by intermittent abdominal pain, altered bowel habits, and other symptoms such as bloating that can have a profound impact on emotional health and quality of life.[6] Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine and includes such disorders as ulcerative colitis and Crohn’s disease.

A new study released in June of this year found that patients with inflammatory bowel disease have an increased incidence of verbal IQ deficit (a reduced ability to recall words). The researchers found evidence of a verbal IQ decrement in both IBD and IBS patients when measured against both healthy controls and against the patients’ own pre-disease IQ scores. The verbal IQ deficit was particularly pronounced in the inflammatory bowel disease patients.[7]

Furthermore, psychiatric disorders especially major depression and anxiety can be seen in up to 94 percent of IBS patients, and the disorder is frequently interconnected with fibromyalgia and chronic fatigue syndrome.[8] The treatments used for IBS patients often are tied as much to emotional health as to gut health. For example, cognitive-behavioral therapy is known to be effective in IBS sufferers.[9]

IBS sufferers demonstrate significantly lower concentrations of the probiotics Bifidobacteria and Lactobacilli compared with healthy controls.[11] While the etiology of IBS remains unclear, researchers believe both inflammatory changes[10] and modifications in the normal gut flora[6] play a role and that probiotics may favorably alter that milieu.

Depression

The role of the leaky gut syndrome in depression is supported by mounting research that has uncovered higher levels of serum antibodies against toxins from pathogenic enterobacteria in patients with depression compared with healthy controls.[12-15] In one study, researchers noted the differences to be so significant that the results could actually be used to diagnose depression with an accuracy rate of 90 percent.[14]

Chronic Fatigue Syndrome

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.[16] More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.[16] More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.[16] As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.[17] Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.[16]

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

Furthermore, psychiatric disorders especially major depression and anxiety can be seen in up to 94 percent of IBS patients, and the disorder is frequently interconnected with fibromyalgia and chronic fatigue syndrome.[8] The treatments used for IBS patients often are tied as much to emotional health as to gut health. For example, cognitive-behavioral therapy is known to be effective in IBS sufferers.[9]

IBS sufferers demonstrate significantly lower concentrations of the probiotics Bifidobacteria and Lactobacilli compared with healthy controls.[11] While the etiology of IBS remains unclear, researchers believe both inflammatory changes[10] and modifications in the normal gut flora[6] play a role and that probiotics may favorably alter that milieu.

Depression

The role of the leaky gut syndrome in depression is supported by mounting research that has uncovered higher levels of serum antibodies against toxins from pathogenic enterobacteria in patients with depression compared with healthy controls.[12-15] In one study, researchers noted the differences to be so significant that the results could actually be used to diagnose depression with an accuracy rate of 90 percent.[14]

Chronic Fatigue Syndrome

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.[16] More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.[16] More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.[16] As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.[17] Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.[16]

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

IBS sufferers demonstrate significantly lower concentrations of the probiotics Bifidobacteria and Lactobacilli compared with healthy controls.[11] While the etiology of IBS remains unclear, researchers believe both inflammatory changes[10] and modifications in the normal gut flora[6] play a role and that probiotics may favorably alter that milieu.

The role of the leaky gut syndrome in depression is supported by mounting research that has uncovered higher levels of serum antibodies against toxins from pathogenic enterobacteria in patients with depression compared with healthy controls.[12-15] In one study, researchers noted the differences to be so significant that the results could actually be used to diagnose depression with an accuracy rate of 90 percent.[14]

Chronic Fatigue Syndrome

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.[16] More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.[16] More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.[16] As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.[17] Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.[16]

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

The link between gut and cognitive health also can be seen in chronic fatigue syndrome. The activation of inflammatory pathways in response to toxins from harmful gut bacteria also underpins a complex illness known as chronic fatigue syndrome, which presents with a broad range of symptoms such as cognitive dysfunction, headaches, muscular tension, and fatigue.[16] More than 40 percent of patients report symptoms that are often part of anxiety and depressive disorders including dizziness, heart palpitations, appetite changes, and shortness of breath.[16] More than 50 percent of patients also meet the diagnostic criteria of IBS. Investigators have reported marked alterations in the intestinal microflora of CFS patients, especially lower levels of Bifidobacteria.[16] As in depression, serum antibody levels against harmful enterobacteria have been found to be greater in CFS patients than healthy controls, and correlate significantly with the severity of illness and to symptoms such as irritable bowel, muscular tension, fatigue, concentration difficulties, and failing memory.[17] Researchers have also recently discovered that gut pathogens in the GI tract of chronic fatigue patients can communicate with the central nervous system by way of vagal nerve sensory fibers, influencing behavior associated with emotion, especially anxiety, at extremely low levels.[16]

Autism

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

Strong Gut = Healthy Brain

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

More clues to a connection between intestinal microflora and brain function come from studies of autism.[18] Many autistic children experience severe dietary and/or GI problems (including abdominal pain, constipation, diarrhea, and bloating). Some studies show that autistic subjects are predisposed to a leaky gut, making the intestines abnormally permeable so that components of digested foods such as cow’s milk and bread are able to interfere directly with the central nervous system.[18] This abnormal gut environment allows the overgrowth of harmful bacteria and yeasts, which can produce toxic molecules and oxidants.[19] While autism remains an extremely challenging disease, researchers believe that some of its related symptoms can be alleviated by removing harmful bacteria from the gut while stimulating those that are more beneficial.

The connection between intestinal and brain health indicates that restoring the health of the intestinal tract can result in cognitive improvements. The first step in enhancing GI health is to consume a good probiotic. This is especially important because levels of probiotic microflora in the gut decline during the normal course of aging. Their integrity can also be impaired through illness, stress, the use of antibiotics and drugs such as NSAIDs and aspirin, physiological alterations in the gut, and changes in diet. Fortunately, mounting research shows that specific probiotics such as Lactobacilli and Bifidobacteria can help to re-colonize the gut and protect intestinal barrier function.

Probiotics can counteract adverse changes in intestinal barrier function, visceral sensitivity, and gut motility, as well as decrease inflammatory cytokines and so positively influence mood in patients whose emotional symptoms and inflammatory immune chemicals are elevated.[16]

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

A recent review quotes Bifidobacterium infantis (B. infantis) as being able to reduce intestinal inflammation, as seen in two randomized controlled trials.[10,20] However, studies are also showing that probiotics have as important a role in cognitive and emotional health as they do in gut health. In an animal study, B. infantis significantly reduced cytokine levels of IFN-gamma, TNF-alpha, and IL-6 compared with controls, as well as markedly increasing plasma concentrations of tryptophan, the precursor to serotonin, supporting its role as a potential antidepressant.[2]

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

In human studies, a probiotic combination containing Lactobacillus acidophilus (L. acidophilus), B. infantis, and Bifidobacterium longum (B. longum) has been shown to relieve neurocognitive symptoms such as short-term memory and ability to concentrate in patients with CFS.[21]

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

The fact that a leaky gut can translate into poor cognitive performance and reduced feelings of well being indicates that combining a good probiotic (such as BioPRO™) with nutrients shown to strengthen gut health can help support both a healthy GI tract and a healthy brain.

Glutamine, oligosaccharides, DGL, N-acetyl glucosamine, marshmallow root, berberine, cabbage, slippery elm, phosphatidylcholine, and gamma oryzanol (all found in GI Cell Support) are nutrients that are especially helpful for strengthening the GI Tract.

Glutamine helps maintain intestinal wall integrity by preventing intestinal hyperpermeability and bacterial translocation.[22] In a recent study, a glutamine-containing preparation in conjunction with a leaky gut diet reduced gut-derived inflammation in 41 CFS patients. More than half of the patients also showed a significant clinical improvement or remission after 10-14 months of treatment.[23] Incorporating additional high-dose glutamine powder along with the glutamine found in GI Cell Support can offer enhanced intestinal support.

Oligosaccharides are often referred to as prebiotics because they stimulate the growth of naturally occurring probiotics such as B. longum, B. infantis, and B. bifidum.[24] DGL, another nutrient known to support GI health, provides an important weapon against Helicobacter pylori, a key cause of stomach ulcers and gastritis.[25-26]

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

Conclusion

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

References

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

2. Desbonnet L, Garrett L, Clarke G, Bienenstock J, Dinan TG. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res. 2008 Dec;43(2):164-74.

3. Forsythe P, Sudo N, Dinan T, Taylor VH, Bienenstock J. Mood and gut feelings. Brain Behav Immun. 2009 May 28.

4. McFarland LV, Dublin S. Meta-analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol. 2008 May 7;14(17):2650-61.

5. Wald A, Rakel D. Behavioral and complementary approaches for the treatment of irritable bowel syndrome. Nutr Clin Pract. 2008 Jun-Jul;23(3):284-92.

6. Hun L. Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. Postgrad Med. 2009 Mar;121(2):119-24.

7. Dancey CP, Attree EA, Stuart G, Wilson C, Sonnet A. Words fail me: the verbal IQ deficit in inflammatory bowel disease and irritable bowel syndrome. Inflamm Bowel Dis. 2009 Jun;15(6):852-7.

8. Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? Gastroenterology. 2002 Apr;122(4):1140-56. 9. Hunt MG, Moshier S, Milonova M. Brief cognitive-behavioral internet therapy for irritable bowel syndrome. Behav Res Ther. 2009 May 20. Published Online Ahead of Print.

10. Brenner DM, Chey WD. Bifidobacterium infantis 35624: a novel probiotic for the treatment of irritable bowel syndrome. Rev Gastroenterol Disord. 2009 Winter;9(1):7-15.

11. Barrett JS, Canale KEK, Gearry RB, Irving PM, Gibson PR. Probiotic effects on intestinal fermentation patterns in patients with irritable bowel syndrome. World J Gastroenterol 2008 August 28;14(32):5020-4.

12. Maes M, Yirmyia R, Noraberg J, et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53.

13. Maes M, Mihaylova I, Kubera M, Leunis JC. An IgM-mediated immune response directed against nitro-bovine serum albumin (nitro-BSA) in chronic fatigue syndrome (CFS) and major depression: evidence that nitrosative stress is another factor underpinning the comorbidity between major depression and CFS. Neuro Endocrinol Lett. 2008 Jun;29(3):313-9.

14. Maes M, Kubera M, Leunis JC. The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. Neuro Endocrinol Lett. 2008 Feb;29(1):117-24.

15. Maes M. The cytokine hypothesis of depression: inflammation, oxidative & nitrosative stress (IO&NS) and leaky gut as new targets for adjunctive treatments in depression. Neuro Endocrinol Lett. 2008 Jun;29(3):287-91.

16. Rao AV, Bested AC, Beaulne TM, et al. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6.

17. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement of gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affect Disord. 2007 Apr;99(1-3):237-40.

18. White JF. Intestinal pathophysiology in autism. Exp Biol Med (Maywood). 2003 Jun;228(6):639-49.

19. Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005 Oct;54(Pt 10):987-91.

20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005 Mar;128(3):541-51.

21. Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4.

22. Miller AL. Therapeutic considerations of L-glutamine: a review of the literature. Altern Med Rev. 1999 Aug;4(4):239-48.

23. Maes M, Leunis JC. Normalization of leaky gut in chronic fatigue syndrome (CFS) is accompanied by a clinical improvement: effects of age, duration of illness and the translocation of LPS from gram-negative bacteria. Neuro Endocrinol Lett. 2008 Dec;29(6):902-10.

24. German JB, Freeman SL, Lebrilla CB, Mills DA. Human milk oligosaccharides: evolution, structures and bioselectivity as substrates for intestinal bacteria. Nestle Nutr Workshop Ser Pediatr Program. 2008;62:205-18; discussion 218-22.

25. Rees WD, Rhodes J, Wright JE, Stamford LF, Bennett A. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol. 1979;14(5):605-7.

26. Larkworthy W, Holgate PF. Deglycyrrhizinized liquorice in the treatment of chronic duodenal ulcer. A retrospective endoscopic survey of 32 patients. Practitioner. 1975 Dec;215(1290):787-92.

27. Salvatore S, Heuschkel R, Tomlin S, et al. A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease. Aliment Pharmacol Ther. 2000 Dec;14(12):1567-79.

28. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.

29. Fukuda K, Hibiya Y, Mutoh M, et al. Inhibition by berberine of cyclooxygenase-2 transcriptional activity in human colon cancer cells. J Ethnopharmacol. 1999;66:227-33.

30. Cheney G (1952). “Vitamin U Therapy of Peptic Ulcer”. California Medicine. 77 (4): 248-52.

31. Stremmel W, Ehehalt R, Autschbach F, Karner M. Phosphatidylcholine for steroid-refractory chronic ulcerative colitis: a randomized trial. Ann Intern Med. 2007 Nov 6;147(9):603-10.

Strengthening the GI Tract to Enhance Cognitive Health

Other GI-strengthening nutrients are N-acetyl glucosamine, important for tissue repair and in augmenting epithelial intestinal defenses in chronic inflammatory bowel disease;[27] Marshmallow root, shown to be effective in protecting mucous membranes from local irritation by virtue of its content of mucilage polysaccharides;[28] Berberine, which can help control inflammation of the GI tract by selectively inhibiting cyclooxygenase-2 (COX-2) expression and blocking the production of proinflammatory cytokines;[29] Cabbage, which has been shown to alleviate pain and significantly reduce healing time in patients with peptic ulcers;[30] Slippery elm, shown to protect the delicate lining of the intestines from ulcers and excess acidity;[28] Phosphatidylcholine, which has shown impressive results in patients with ulcerative colitis by reducing their dependence on corticosteroids;[31] and Gamma oryzanol, which contributes ferulic esters derived from rice bran oil and is highly regarded in Japan to enhance gastric and ileal movement.

A healthy GI tract is not just important for efficient digestion but is also a key factor in ensuring optimal brain health. However, probiotic microorganisms that protect the gut decline with age, increasing our susceptibility to a breakdown in the gut’s protective mucosal barrier. Fortunately, research shows that specific probiotics and targeted nutrients can help prevent this breakdown, improving both gut integrity and brain health.

1. Coates MD, Mahoney CR, Linden DR, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004 Jun;126(7):1657-64.

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