Beyond Probiotics
Hidden Causes of GI Dysfunction
By Chris D. Meletis, ND
Often, in the absence of overt disease, the extent of an individual’s colon-supporting supplement regimen consists exclusively of consuming a good probiotic. Yet, in order for the good bacteria found in probiotics to flourish in the colonic environment, there are other steps we need to take to ensure our gut is hospitable to the friendly bacteria our bodies need to thrive—regardless of whether an individual is healthy or whether that individual suffers from irritable bowel syndrome or another gastrointestinal disease. The colon is essentially our body’s compost pile, used to nurture our garden of friendly flora.
There are two often-overlooked aspects of gut health that are essential to keeping our colon healthy and to ensure it remains a hospitable environment where good bacteria can thrive. First, gut health is linked to a substance called butyrate. If the intestine isn’t working at its optimal best, levels of butyrate can undergo a decline, putting individuals at risk for colon cancer. Butyrate levels are closely tied to the health of the intestine and to levels of friendly flora found in the gut.
A second aspect of gut health is known as intestinal permeability. This can be a huge factor, even in seemingly healthy individuals. Intestinal permeability refers to the potential for nutrients and bacteria to escape through a weakened intestinal wall. When intestinal permeability is increased, food and nutrient absorption is impaired. Dysfunction in intestinal permeability can result in leaky gut syndrome, where larger molecules in the intestines pass through into the blood. This can trigger immediate damage and immune system reactions since these large molecules are perceived as foreign. Progressive damage occurs to the intestinal lining, eventually allowing disease-causing bacteria, undigested food particles, and toxins to pass directly into the bloodstream.
Dysfunctions in intestinal permeability are associated not only with intestinal diseases such as ulcerative colitis, irritable bowel syndrome and Crohn’s disease, but also with chronic fatigue syndrome, psoriasis, food allergies, autoimmune disease and arthritis. Impaired intestinal permeability also occurs in patients undergoing chemotherapy and in heart disease patients.
I briefly discussed intestinal permeability in my last article on GI health. In this article, I will go into further detail about this damaging aspect of intestinal health and explain how increasing butyrate can be a powerful tool in not only restoring ideal colon function but also improving energy levels and the overall health of the body.
Building Butyrate for Colonic Health
Butyrate, a major short-chain fatty acid produced in the human gut by bacterial fermentation of dietary fiber, exhibits strong tumor suppressing activity. Butyrate is an important energy source for cells lining the intestine and plays a role in the maintenance of colonic balance. Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis. Butyrate also reinforces various components that play a role in the colonic defense barrier and decrease oxidative stress. In addition, butyrate may promote satiety.1
Low levels of butyrate are linked to increased risk of colon cancer. A loss of balance in the colon caused by either genetic mutations or environmental factors such as dietary habits can increase the risk for the formation of aberrant crypt foci (the earliest identifiable cancerous lesions in the colon) and ultimately the development of colon cancer. Evidence exists that butyrate reduces the number and the size of aberrant crypt foci in the colon.2
Butyrate’s inhibition of colon cancer is thought to arise from its ability to act as a natural histone deacetylase inhibitor, which results in activation of certain genes known to induce apoptosis (cell death) in cancer cells.2
Low butyrate levels occur in healthy humans prior to the onset of disease, often in response to a poor diet high in sugar and low in fiber. Low butyrate levels also are found in disease states such as ulcerative colitis and Crohn’s disease, especially in patients with moderate to severe mucosal inflammation.3 The monocarboxylate transporter helps colon cells uptake butyrate and during inflammatory bowel disease the monocarboxylate transporter is impaired, preventing the butyrate from getting to the cells.4
The Colonic Barrier and Overall Health
Abnormal intestinal permeability, like low butyrate levels, is another concern that can serve as a hidden reason why we might not be feeling our optimal best. A dysfunction can present in intestinal permeability when an individual is consuming a less than optimal diet or due to other factors such as psychological stress.5
Intestinal permeability, in fact, may be the main cause behind why the body becomes sensitive to a particular type of food. One group of researchers evaluated the intestinal permeability in subjects with adverse reactions to food. Twenty-one subjects with a food allergy and 20 with food hypersensitivity who were on allergen-free diets were enrolled and divided into four groups according to the seriousness of their referred clinical symptoms. The study authors found statistically significant differences in intestinal permeability in subjects with food allergy or hypersensitivity compared to control patients. The worse the intestinal permeability, the more serious the clinical symptoms in patients with food allergy and hypersensitivity.6
According to the researchers, “The present data demonstrate that impaired intestinal permeability, measured in our conditions, is present in all subjects with adverse reactions to food. In addition, for the first time, we report a statistically significant association between the severity of referred clinical symptoms and the increasing of Intestinal Permeability Index. These data reveal that intestinal permeability is not strictly dependent on IgE-mediated processes but could better be related to other mechanisms involved in early food sensitization, as breast-feeding, or microbial environment that influence the development of oral tolerance in early infancy.”
Impaired intestinal permeability is often linked with GI diseases such as ulcerative colitis and Crohn’s. However, new research is unearthing a surprising link between malfunctions in the colonic barrier and a number of non-gastrointestinal conditions such as heart disease.
In a recent study, scientists evaluated the function of the gut in 22 patients with chronic heart failure (CHF) and 22 control subjects. Chronic heart failure patients, compared with control patients, had a 35 percent increase of small intestinal permeability and a 210 percent increase of large intestinal permeability. Additionally, higher concentrations of adherent bacteria were found within mucus of CHF patients compared to control subjects.7
The researchers determined, “Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.”
Strengthening the Colon
Raising butyrate levels and reducing the permeability of the intestinal barrier can have far reaching consequences for our health that extend beyond the gastrointestinal tract. Consequently, nutritional support is key.
Increasing fiber intake through consumption of a fiber supplement is one of the easiest ways to increase butyrate levels in the body. Fiber is well known for its ability to protect against colon cancer and its ability to raise butyrate levels is thought to be one of the main ways in which it protects the colon. The benefits of dietary fiber on inflammatory bowel disease may also be related to the production of butyrate that occurs when fiber is fermented in the colon. Butyrate appears to decrease the inflammatory response.8
Combining fiber and a good probiotic with specific botanicals, amino acids and fatty acids known to reduce intestinal permeability can provide additional support for the colon. Phosphatidylcholine, for example, can enhance butyrate’s ability to inhibit colon cancer cells, and therefore works well with fiber to strengthen the intestinal environment.9
The amino acid glutamine is one of the most powerful tools for reducing intestinal permeability, thereby protecting the body against the negative consequences of a leaky gut. In a recent review, researchers studied the medical literature to determine if glutamine was effective in reducing intestinal permeability in critically ill patients. In this group of patients, intestinal permeability can have particularly lethal consequences, causing bacteremia, sepsis, and multiple organ failure syndrome. After studying the medical literature, the scientists concluded that glutamine administration by the intravenous or oral route has a protective effect that prevents or reduces the intensity of the increase in intestinal permeability. Glutamine also reduces the frequency of systemic infections.10
Another group of researchers drew a similar conclusion after studying chemotherapy patients with gastrointestinal cancer. In this group of subjects, oral glutamine decreased intestinal permeability and maintained the intestinal barrier.11
Berberine is another substance that can help reduce intestinal permeability and stop beneficial nutrients from escaping through the intestinal wall.12 Berberine also is highly effective at inhibiting the growth of pathogens that invade the colon.
In my clinical practice, I have found that the best way to improve butyrate levels and reduce intestinal permeability is to combine a good fiber supplement with a supplement that contains phosphatidylcholine, L-glutamine, berberine, deglycyrrhizinated licorice (DGL), N-acetyl glucosamine, marshmallow (Althaea officinalis) root, cabbage powder, slippery elm (Ulmus rubra) bark, and gamma oryzanol. This often results in an increased level of friendly flora in the gut and maximizes the effectiveness of any probiotic supplement consumed. After undertaking this approach, patients often report improvement in their gastrointestinal tract and increased overall health and energy.
Conclusion
The gut uses a disproportionate amount of energy (about 25 percent of total oxygen consumption) for the size of the tissue (about 6 percent of body weight).13 Consequently, it’s especially important to provide this part of the body with as much support as possible. Fiber, probiotics, the amino acid L-glutamine, the fatty acid phosphatidylcholine, N-acetyl glucosamine, deglycyrrhizinated licorice and select botanicals such as marshmallow, berberine, cabbage powder and slippery elm can help raise levels of butyrate and reduce intestinal permeability. This approach can result in a healthier colon, improved energy and enhanced overall health.
References
1. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.
2. Kim YS, Milner JA. Dietary modulation of colon cancer risk. J Nutr. 2007 Nov;137(11 Suppl):2576S-2579S.
3. Duffy MM, Regan MC, Ravichandran P, O’Keane C, Harrington MG, Fitzpatrick JM, O’Connell PR. Mucosal metabolism in ulcerative colitis and Crohn’s disease. Dis Colon Rectum. 1998 Nov;41(11):1399-405.
4. Thibault R, De Coppet P, Daly K, Bourreille A, Cuff M, Bonnet C, Mosnier JF, Galmiche JP, Shirazi-Beechey S, Segain JP. Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology. 2007 Dec;133(6):1916-27.
5. Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, McKay DM, Soderholm JD, Perdue MH, Sherman PM. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut. 2006 Nov;55(11):1553-60. Epub 2006 Apr 25.
6. Ventura MT, Polimeno L, Amoruso AC, Gatti F, Annoscia E, Marinaro M, Di Leo E, Matino MG, Buquicchio R, Bonini S, Tursi A, Francavilla A. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis. 2006 Oct;38(10):732-6.
7. Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, Schroedl W, Karhausen T, Doehner W, Rauchhaus M, Poole-Wilson P, Volk HD, Lochs H, Anker SD. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007 Oct 16;50(16):1561-9.
8. Rose DJ, DeMeo MT, Keshavarzian A, Hamaker BR. Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern. Nutr Rev. 2007 Feb;65(2):51-62.
9. Hossain Z, Konishi M, Hosokawa M, Takahashi K. Effect of polyunsaturated fatty acid-enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells. Cell Biochem Funct. 2006 Mar-Apr;24(2):159-65.
10. De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005 May;33(5):1175-8.
11. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Jan;9(1):59-61. [Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy] [Article in Chinese]. Jiang HP, Liu CA.
12. Taylor CT, Winter DC, Skelly MM, O’Donoghue DP, O’Sullivan GC, Harvey BJ, Baird AW. Berberine inhibits ion transport in human colonic epithelia. Eur J Pharmacol. 1999 Feb 26;368(1):111-8.
13. Britton R, Krehbiel C. Nutrient metabolism by gut tissues. J Dairy Sci. 1993 Jul;76(7):2125-31.
Hidden Causes of GI Dysfunction
By Chris D. Meletis, ND
Often, in the absence of overt disease, the extent of an individual’s colon-supporting supplement regimen consists exclusively of consuming a good probiotic. Yet, in order for the good bacteria found in probiotics to flourish in the colonic environment, there are other steps we need to take to ensure our gut is hospitable to the friendly bacteria our bodies need to thrive—regardless of whether an individual is healthy or whether that individual suffers from irritable bowel syndrome or another gastrointestinal disease. The colon is essentially our body’s compost pile, used to nurture our garden of friendly flora.
There are two often-overlooked aspects of gut health that are essential to keeping our colon healthy and to ensure it remains a hospitable environment where good bacteria can thrive. First, gut health is linked to a substance called butyrate. If the intestine isn’t working at its optimal best, levels of butyrate can undergo a decline, putting individuals at risk for colon cancer. Butyrate levels are closely tied to the health of the intestine and to levels of friendly flora found in the gut.
A second aspect of gut health is known as intestinal permeability. This can be a huge factor, even in seemingly healthy individuals. Intestinal permeability refers to the potential for nutrients and bacteria to escape through a weakened intestinal wall. When intestinal permeability is increased, food and nutrient absorption is impaired. Dysfunction in intestinal permeability can result in leaky gut syndrome, where larger molecules in the intestines pass through into the blood. This can trigger immediate damage and immune system reactions since these large molecules are perceived as foreign. Progressive damage occurs to the intestinal lining, eventually allowing disease-causing bacteria, undigested food particles, and toxins to pass directly into the bloodstream.
Dysfunctions in intestinal permeability are associated not only with intestinal diseases such as ulcerative colitis, irritable bowel syndrome and Crohn’s disease, but also with chronic fatigue syndrome, psoriasis, food allergies, autoimmune disease and arthritis. Impaired intestinal permeability also occurs in patients undergoing chemotherapy and in heart disease patients.
I briefly discussed intestinal permeability in my last article on GI health. In this article, I will go into further detail about this damaging aspect of intestinal health and explain how increasing butyrate can be a powerful tool in not only restoring ideal colon function but also improving energy levels and the overall health of the body.
Building Butyrate for Colonic Health
Butyrate, a major short-chain fatty acid produced in the human gut by bacterial fermentation of dietary fiber, exhibits strong tumor suppressing activity. Butyrate is an important energy source for cells lining the intestine and plays a role in the maintenance of colonic balance. Butyrate exerts potent effects on a variety of colonic mucosal functions such as inhibition of inflammation and carcinogenesis. Butyrate also reinforces various components that play a role in the colonic defense barrier and decrease oxidative stress. In addition, butyrate may promote satiety.1
Low levels of butyrate are linked to increased risk of colon cancer. A loss of balance in the colon caused by either genetic mutations or environmental factors such as dietary habits can increase the risk for the formation of aberrant crypt foci (the earliest identifiable cancerous lesions in the colon) and ultimately the development of colon cancer. Evidence exists that butyrate reduces the number and the size of aberrant crypt foci in the colon.2
Butyrate’s inhibition of colon cancer is thought to arise from its ability to act as a natural histone deacetylase inhibitor, which results in activation of certain genes known to induce apoptosis (cell death) in cancer cells.2
Low butyrate levels occur in healthy humans prior to the onset of disease, often in response to a poor diet high in sugar and low in fiber. Low butyrate levels also are found in disease states such as ulcerative colitis and Crohn’s disease, especially in patients with moderate to severe mucosal inflammation.3 The monocarboxylate transporter helps colon cells uptake butyrate and during inflammatory bowel disease the monocarboxylate transporter is impaired, preventing the butyrate from getting to the cells.4
The Colonic Barrier and Overall Health
Abnormal intestinal permeability, like low butyrate levels, is another concern that can serve as a hidden reason why we might not be feeling our optimal best. A dysfunction can present in intestinal permeability when an individual is consuming a less than optimal diet or due to other factors such as psychological stress.5
Intestinal permeability, in fact, may be the main cause behind why the body becomes sensitive to a particular type of food. One group of researchers evaluated the intestinal permeability in subjects with adverse reactions to food. Twenty-one subjects with a food allergy and 20 with food hypersensitivity who were on allergen-free diets were enrolled and divided into four groups according to the seriousness of their referred clinical symptoms. The study authors found statistically significant differences in intestinal permeability in subjects with food allergy or hypersensitivity compared to control patients. The worse the intestinal permeability, the more serious the clinical symptoms in patients with food allergy and hypersensitivity.6
According to the researchers, “The present data demonstrate that impaired intestinal permeability, measured in our conditions, is present in all subjects with adverse reactions to food. In addition, for the first time, we report a statistically significant association between the severity of referred clinical symptoms and the increasing of Intestinal Permeability Index. These data reveal that intestinal permeability is not strictly dependent on IgE-mediated processes but could better be related to other mechanisms involved in early food sensitization, as breast-feeding, or microbial environment that influence the development of oral tolerance in early infancy.”
Impaired intestinal permeability is often linked with GI diseases such as ulcerative colitis and Crohn’s. However, new research is unearthing a surprising link between malfunctions in the colonic barrier and a number of non-gastrointestinal conditions such as heart disease.
In a recent study, scientists evaluated the function of the gut in 22 patients with chronic heart failure (CHF) and 22 control subjects. Chronic heart failure patients, compared with control patients, had a 35 percent increase of small intestinal permeability and a 210 percent increase of large intestinal permeability. Additionally, higher concentrations of adherent bacteria were found within mucus of CHF patients compared to control subjects.7
The researchers determined, “Chronic heart failure is a multisystem disorder in which intestinal morphology, permeability, and absorption are modified. Increased intestinal permeability and an augmented bacterial biofilm may contribute to the origin of both chronic inflammation and malnutrition.”
Strengthening the Colon
Raising butyrate levels and reducing the permeability of the intestinal barrier can have far reaching consequences for our health that extend beyond the gastrointestinal tract. Consequently, nutritional support is key.
Increasing fiber intake through consumption of a fiber supplement is one of the easiest ways to increase butyrate levels in the body. Fiber is well known for its ability to protect against colon cancer and its ability to raise butyrate levels is thought to be one of the main ways in which it protects the colon. The benefits of dietary fiber on inflammatory bowel disease may also be related to the production of butyrate that occurs when fiber is fermented in the colon. Butyrate appears to decrease the inflammatory response.8
Combining fiber and a good probiotic with specific botanicals, amino acids and fatty acids known to reduce intestinal permeability can provide additional support for the colon. Phosphatidylcholine, for example, can enhance butyrate’s ability to inhibit colon cancer cells, and therefore works well with fiber to strengthen the intestinal environment.9
The amino acid glutamine is one of the most powerful tools for reducing intestinal permeability, thereby protecting the body against the negative consequences of a leaky gut. In a recent review, researchers studied the medical literature to determine if glutamine was effective in reducing intestinal permeability in critically ill patients. In this group of patients, intestinal permeability can have particularly lethal consequences, causing bacteremia, sepsis, and multiple organ failure syndrome. After studying the medical literature, the scientists concluded that glutamine administration by the intravenous or oral route has a protective effect that prevents or reduces the intensity of the increase in intestinal permeability. Glutamine also reduces the frequency of systemic infections.10
Another group of researchers drew a similar conclusion after studying chemotherapy patients with gastrointestinal cancer. In this group of subjects, oral glutamine decreased intestinal permeability and maintained the intestinal barrier.11
Berberine is another substance that can help reduce intestinal permeability and stop beneficial nutrients from escaping through the intestinal wall.12 Berberine also is highly effective at inhibiting the growth of pathogens that invade the colon.
In my clinical practice, I have found that the best way to improve butyrate levels and reduce intestinal permeability is to combine a good fiber supplement with a supplement that contains phosphatidylcholine, L-glutamine, berberine, deglycyrrhizinated licorice (DGL), N-acetyl glucosamine, marshmallow (Althaea officinalis) root, cabbage powder, slippery elm (Ulmus rubra) bark, and gamma oryzanol. This often results in an increased level of friendly flora in the gut and maximizes the effectiveness of any probiotic supplement consumed. After undertaking this approach, patients often report improvement in their gastrointestinal tract and increased overall health and energy.
Conclusion
The gut uses a disproportionate amount of energy (about 25 percent of total oxygen consumption) for the size of the tissue (about 6 percent of body weight).13 Consequently, it’s especially important to provide this part of the body with as much support as possible. Fiber, probiotics, the amino acid L-glutamine, the fatty acid phosphatidylcholine, N-acetyl glucosamine, deglycyrrhizinated licorice and select botanicals such as marshmallow, berberine, cabbage powder and slippery elm can help raise levels of butyrate and reduce intestinal permeability. This approach can result in a healthier colon, improved energy and enhanced overall health.
References
1. Hamer HM, Jonkers D, Venema K, Vanhoutvin S, Troost FJ, Brummer RJ. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19.
2. Kim YS, Milner JA. Dietary modulation of colon cancer risk. J Nutr. 2007 Nov;137(11 Suppl):2576S-2579S.
3. Duffy MM, Regan MC, Ravichandran P, O’Keane C, Harrington MG, Fitzpatrick JM, O’Connell PR. Mucosal metabolism in ulcerative colitis and Crohn’s disease. Dis Colon Rectum. 1998 Nov;41(11):1399-405.
4. Thibault R, De Coppet P, Daly K, Bourreille A, Cuff M, Bonnet C, Mosnier JF, Galmiche JP, Shirazi-Beechey S, Segain JP. Down-regulation of the monocarboxylate transporter 1 is involved in butyrate deficiency during intestinal inflammation. Gastroenterology. 2007 Dec;133(6):1916-27.
5. Zareie M, Johnson-Henry K, Jury J, Yang PC, Ngan BY, McKay DM, Soderholm JD, Perdue MH, Sherman PM. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut. 2006 Nov;55(11):1553-60. Epub 2006 Apr 25.
6. Ventura MT, Polimeno L, Amoruso AC, Gatti F, Annoscia E, Marinaro M, Di Leo E, Matino MG, Buquicchio R, Bonini S, Tursi A, Francavilla A. Intestinal permeability in patients with adverse reactions to food. Dig Liver Dis. 2006 Oct;38(10):732-6.
7. Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, Schroedl W, Karhausen T, Doehner W, Rauchhaus M, Poole-Wilson P, Volk HD, Lochs H, Anker SD. Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol. 2007 Oct 16;50(16):1561-9.
8. Rose DJ, DeMeo MT, Keshavarzian A, Hamaker BR. Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern. Nutr Rev. 2007 Feb;65(2):51-62.
9. Hossain Z, Konishi M, Hosokawa M, Takahashi K. Effect of polyunsaturated fatty acid-enriched phosphatidylcholine and phosphatidylserine on butyrate-induced growth inhibition, differentiation and apoptosis in Caco-2 cells. Cell Biochem Funct. 2006 Mar-Apr;24(2):159-65.
10. De-Souza DA, Greene LJ. Intestinal permeability and systemic infections in critically ill patients: effect of glutamine. Crit Care Med. 2005 May;33(5):1175-8.
11. Zhonghua Wei Chang Wai Ke Za Zhi. 2006 Jan;9(1):59-61. [Protective effect of glutamine on intestinal barrier function in patients receiving chemotherapy] [Article in Chinese]. Jiang HP, Liu CA.
12. Taylor CT, Winter DC, Skelly MM, O’Donoghue DP, O’Sullivan GC, Harvey BJ, Baird AW. Berberine inhibits ion transport in human colonic epithelia. Eur J Pharmacol. 1999 Feb 26;368(1):111-8.
13. Britton R, Krehbiel C. Nutrient metabolism by gut tissues. J Dairy Sci. 1993 Jul;76(7):2125-31.