Interactions of the Gut Microflora and the Host in Toxicology

Abstract

Food components and ingested chemicals may be metabolized in the gut, not only by digestive and intestinal mucosal enzymes, but also by the resident bacteria, which are found in greatest numbers in the large intestine. The gut microflora is a large (about 10¹¹ organisms per g colon contents) and diverse (over 400 species) population of organisms and possesses a correspondingly diverse range of metabolic activities, including reductions, hydrolyses and degradations. In many cases, these reactions both complement and antagonize those of the liver, which are mainly oxidative and synthetic. The metabolism, by the gut flora, of chemicals ingested in food or secreted in bile can have numerous toxicological sequelae, including activation to more toxic, mutagenic or carcinogenic derivatives, detoxication and enterohepatic circulation. These toxicological consequences may be modified by changes in the flora due to diet, drugs and interindividual differences. Examples presented of the interaction between the gut flora and its host are the influence of intestinal bacteria on hepatic tumor incidence in mice, the effect of bacterial hydrolysis of rutin on the activity of hepatic enzymes which activate dietary carcinogens, and the role of the gut flora in demethylation and detoxication of methylmercury.