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Intestinal Dysbiosis and the Causes of Disease

© 1995 Leo Galland M.D., F.A.C.N., Stephen Barrie N.D.

(3 of 9)  


Most adverse effects of the indigenous gut flora are caused by the intense metabolic activity of luminal organisms. The following are associated with Putrefaction dysbiosis:

1. The enzyme urease, found in Bacteroides, Proteus and Klebsiella species, and induced in those organisms by a diet high in meat, hy- drolyzes urea to ammonia, raising stool pH. A relatively high stool pH is associated with a higher prevalence of colon cancer(7).

2. Bacterial decarboxylation of amino acids yields vasoactive and neurotoxic amines, including histamine, octopamine, tyramine and tryptamine; these are absorbed through the portal circulation and deaminated in the liver. In severe cirrhosis they reach the systemic circulation and contribute to the encephalopathy and hypotension of hepatic failure(1).

3. Bacterial tryptophanase degrades tryptophan to carcinogenic phe- nols, and, like urease, is induced by a high meat diet(8).

4. Bacterial enzymes like beta-glucuronidase hydrolyze conjugated es- trogens and bile acids. Hepatic conjugation and biliary excretion is an important mechanism for regulating estrogen levels in the body. Bacte- rial deconjugation increases the enterohepatic recirculation of estrogen. A Western diet increases the level of deconjugating enzymes in stool, lowers estrogen levels in stool and raises estrogen levels in blood and urine, possibly contributing to the development of breast cancer(6).

5. Beta-glucuronidase and other hydrolytic bacterial enzymes also deconjugate bile acids.

Deconjugated bile acids are toxic to the colonic epithelium and cause diarrhea. They or their metabolites appear to be carcinogenic and are thought to contribute to the development of colon cancer(6,9) and to ulcerative colitis(10). Gut bacteria also reduce primary bile acids like cholate and chenodeoxycholate to secondary bile acids like deoxycholate (DCA) and lithocholate. The secondary bile acids are ab- sorbed less efficiently than primary bile acids and are more likely to contribute to colon carcinogenesis. The prevalence of colon cancer is proportional to stool concentration of DCA.

Not all bacterial enzyme activity is harmful to the host. Fermenta- tion of soluble flber by Bifidobacteria sp. yields SCFA. Recent interest has focused on the beneficial role of short-chain fatty acids like buty- rate in nourishing healthy colonic mucosal cells. Butyrate has been shown to induce differentiation of neoplastic cells(l1), decreased ab- sorption of ammonia from the intestine(1), decreased inflammation in ulcerative colitis(12) and, following absorption, decreased cholesterol synthesis in the liver(7). Butyrate lowers the stool pH. A relatively low stool pH is associated with protection against colon cancer(S). The principal source of colonic butyrate is fermentation of soluble fiber by colonic anaerobes. Thus, putrefaction dysbiosis results from the inter- play of bacteria and diet in their effects on health and disease.

Fermentation
This is a condition of carbohydrate intolerance induced by overgrowth of endogenous bacteria in the stomach, small intestine and cecum. The causes and effects of small bowel bacterial overgrowth have been well characterized.

Bacterial overgrowth is promoted by gastric hypochlorhydria, by stasis due to abnormal motility, strictures, fistulae and surgical blind loops, by immune deficiency or by malnutrition( 13). Small bowel parasitosis may also predispose to bacterial overgrowth(4). Some of the damage resulting from small bowel bacterial overgrowth is pro- duced by the action of bacterial proteases which degrade pancreatic and intestinal brush border enzymes causing pancreatic insufficiency, mucosal damage and malabsorption. In more severe cases the intesti- nal villi are blunted and broadened and mononuclear cells infiltrate the lamina propria. Increased fecal nitrogen leads to hypoalbumine- mia. Bacterial consumption of cobalamin lowers blood levels of vita- min B12. Bile salt dehydroxylation impairs micelle formation(10). Endotoxemia resulting from bacterial overgrowth contributes to hep- atic damage in experimental animals(14).


Copyright © 1995

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Leo Galland, M.D. has received international recognition as a leader in the field of Nutritional Medicine for the past 20 years. A board-certified internist, Dr. Galland is a Fellow of the ...more

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