The Role of Intestinal Bacteria in the Development of Dietary Cirrhosis in Rats

Abstract

Antibiotics delay the development of dietary hepatic necrosis and fibrosis in rats (1,2). This protective effect is lost after the intestinal flora develop resistance to the antibiotic. Furthermore, rats fed a necrogenic diet, but maintained in a germ-free environment, do not develop liver necrosis (2). Clearly, then, bacteria are involved in the development of necrosis or fibrosis. But the way in which bacteria are involved is obscure. Gyorgy (1) believes that the metabolic abnormalities which lead to cirrhosis are enhanced by bacterial activity. At the same time he suggests that antibiotics delay the development of cirrhosis by an undefined protective effect upon the metabolic mechanisms.Experiments were done in this laboratory to explore more precisely the role of the intraintestinal bacteria in the development of cirrhosis in rats. For this objective it was considered necessary to use non-absorbable 1 as well as absorbable antibiotics, in order to distinguish between a systemic effect of antibiotics and their effect upon the intraintestinal flora. In this communication we report the results of the effect of orally administered antibiotics upon rate of growth, survival time, and the pathological changes in the liver of rats on a choline-deficient diet. MethodMale rats of the Wistar strain, each weighing 95 to 100 gin., were housed in an air-conditioned laboratory in wire cages with raised screen bottoms.

The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases

“…It has been shown that antibiotics prevent hepatic injury and fibrosis induced by CCl4 treatment or a cholinedeficient diet, and that LPS enhances hepatic fibrosis induced by a MCCD [74,75]. Treatment of mice with nonabsorbable broad-spectrum antibiotics also resulted in a clear reduction in the fibrotic response of mice, upon bile duct ligation [21].…”

Toll-like receptors as targets in chronic liver diseases

“…It is believed that changes in intestinal motility, subsequent alterations of the intestinal microbiota, decreased mucosal integrity and suppressed immunity in hepatic fibrosis contribute to a failure of the intestinal mucosal barrier and cause increases in bacterial translocation and LPS levels in later stages of hepatic fibrosis and cirrhosis 30 119 – 123. Studies from the 1950s have shown that antibiotics prevent hepatic injury and fibrosis induced by CCl 4 treatment or a choline-deficient diet, and that endotoxin enhances hepatic fibrosis induced by a choline-deficient diet 124 125. Recent studies using TLR4-mutant as well as gut-sterilised, CD14- and LPS binding protein (LBP)-deficient mice have demonstrated the crucial role for the LPS–TLR4 pathway in hepatic fibrogenesis 47 126.…”

Advances in alcoholic liver disease

“…It is well understood that the gut flora and gut-derived toxins play a critical role in the development of liver disease and its complications [29,[31][32][33][34][35][36][37]. Indeed, more than a half century ago, it was shown that germ-free rodents or rodents treated with antibiotics to "sterilize the gut" were resistant to nutritional and toxin-induced liver injury.…”