Mucosal biotransformation of toxins in the gut.

Abstract

A major fraction of foreign compounds entering the body is absorbed through the gastrointestinal tract in ingested food and beverages as well as in the swallowed respiratory mucus carrying part of the chemical loading of inspired air. The large surface area provides conditions for efficient absorption. The mucosa, however, forms an active barrier. There are several enzymes capable of oxidizing, reducing and hydrolysing xenobiotics as well as many enzymes conjugating either the compounds themselves or their reaction products. In the rat, the monooxygenase and uridine diphosphate glucuronosyltransferase activities appear to be highest in the oral end of the gut and decrease aborally. Compared with the hepatic activities the mucosal monooxygenase levels are lower, but the UDP-glucuronosyltransferase activities may even be higher than in the liver. The mucosal biotransformation activity is inducible. Within the gut mucosa the highest activities are close to the villus tips. Thus functional maturation of the cells in biotransformation appears to occur when cells are moving up from the crypts. The microvilli of the cells appear to be inactive in mono-oxygenation and glucuronidation. The metabolic products generated within the mucosal cells are released either into the blood or to the gut lumen. The xenobiotics and their metabolites meet in the lumen a rich bacterial flora. Microbes have high metabolic capacity in hydrolysis and reduction. These transformation products are absorbed again loading the host.