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

Abstract

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.

Normal neonatal microbiome variation in relation to environmental factors, infection and allergy

“…Using an in-vitro model of the human gut microbiome, Diaz-Bone and van de Wiele [42] found that normal human intestinal bacteria metabolize environmental contaminants, turning polycyclic aromatic hydrocarbons into bioactive estrogen-like molecules and transforming metals into volatile, and sometimes toxic, products [43] that can affect the gut’s species balance and function, a condition known as dysbiosis. One study found that dysbiosis can potentially result from bismuth exposure, commonly found in cosmetics and Pepto-Bismol, when Methanobrevibacter smithii , a normal gut inhabitant, transforms bismuth into a form that is toxic to Bacteroides thetaiotaomicron, a beneficial resident that mediates infant dietary transition from breastmilk to starches, and aids the formation of the intestinal mucosal barrier that protects against pathogens [44 ▪ ]. Hence, early-life toxicant exposure could shift the microbial balance, potentially affecting both immune and microbiome development.…”

Medical Use of Bismuth: the Two Sides of the Coin

“…A MIC 50 of 17-30 nM of TMBi was determined. The study by Bialek et al [45] also showed the inhibitory effects of soluble, partly methylated mono-and dimethylbismuth with a MIC 50 also in the low nM range. In contrast, the MIC 50 of CBS is four orders of magnitude higher, demonstrating the greater antibacterial effect of methylated bismuth derivatives relative to inorganic derivatives used in medical applications.…”

“…The formation of toxic TMBi in the human colon may also affect the physiological gut microbiota, as indicated by ex situ experiments performed by Meyer et al in 2008 and later by Bialek et al [41,45]. Both studies demonstrated growth impairment of pure cultures of Bacteroides thetaiotaomicron, a representative of the physiological gut microbiota, by TMBi.…”