Production of toxic volatile trimethylbismuth by the intestinal microbiota of mice.

The biotransformation of metals and metalloids into their volatile methylated derivatives by microbes growing under anaerobic conditions (e.g., the mammalian intestinal microbiota) plays an important role in spreading these compounds in the environment. In this paper, we could show that the presence of an intact intestinal microbiota of mice provides the conditio sine qua non for the production of these mostly toxic derivatives. To document the indispensible role of the intestinal microbiota in methylating metals and metalloids to volatile derivatives under in vivo conditions, we compared the methylation capability of conventionally raised (CONV) and germ-free (GF) B6-mice fed with chow containing colloidal bismuth subcitrate (CBS) as the starting material for the formation of volatile methylated metal(loid)s. Permethylated volatile trimethylbismuth ((CH(3))(3)Bi) was only detected in the blood of the conventionally raised mice. Concomitantly, a higher bismuth concentration was found in organs such as liver, lung, testicles, and brain of the CONV mice as compared to those of GF mice (P > 0.01), strongly suggesting a correlation between the intestinal biomethylation of bismuth and its accumulation in mammalian tissues.

Toxicity of Methylated Bismuth Compounds Produced by Intestinal Microorganisms to Bacteroides thetaiotaomicron, a Member of the Physiological Intestinal Microbiota.

Methanoarchaea have an outstanding capability to methylate numerous metal(loid)s therefore producing toxic and highly mobile derivatives. Here, we report that the production of methylated bismuth species by the methanoarchaeum Methanobrevibacter smithii, a common member of the human intestine, impairs the growth of members of the beneficial intestinal microbiota at low concentrations. The bacterium Bacteroides thetaiotaomicron, which is of great importance for the welfare of the host due to its versatile digestive abilities and its protective function for the intestine, is highly sensitive against methylated, but not against inorganic, bismuth species. The level of methylated bismuth species produced by the methanoarchaeum M. smithii in a coculture experiment causes a reduction of the maximum cell density of B. thetaiotaomicron. This observation suggests that the production of methylated organometal(loid) species in the human intestine, caused by the activity of methanoarchaea, may affect the health of the host. The impact of the species to reduce the number of the physiological intestinal microbiota brings an additional focus on the potentially harmful role of methanoarchaea in the intestine of a higher organism.