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). |