Biotransformation of metal(loid)s by intestinal microorganisms

Many metals and metalloids undergo complex biotransformation processes by microorganisms in the environment, namely, Ge, As, Se, Cd, In, Sn, Sb, Te, Hg, Tl, Pb, Bi, and Po. Though the human intestine harbors a highly diverse and metabolically active microbial community, the knowledge on metal(loid) biotransformation by gut microbiota is limited. Microbial metal(loid) metabolism in the gut is highly relevant when assessing health risks from oral exposure, as both the bioavailability and the toxicity of the ingested compound can be modulated. This review gathers and compares a broad selection of scientific studies on the intestinal biotransformation of metal(loid)s. It can be inferred that metal(loid) biotransformation by intestinal microbiota is a common process, resulting in both beneficial and adverse toxicological effects. Whereas for Hg the intestinal demethylation of methylmercury results in enhanced elimination, highly bioavailable and toxic arsenic and Bi species are formed by intestinal microorganisms. In either case, we conclude that the gut microbial potency should be considered to be taken up in toxicokinetic studies and models for assessing the health risks of oral metal(loid) exposure. This will allow the relevance of intestinal metal(loid) biotransformation to be assessed for human health risks

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

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 ((CH3)3Bi) 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

The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants

Biovolatilization of metal(loid)s by intestinal microorganisms in the simulator of the human intestinal microbial ecosystem

Methylation and hydrogenation of metal(loid)s by microorganisms are widespread and well-known processes in the environment by which mobility and in most cases toxicity are significantly enhanced in comparison to inorganic species. The human gut contains highly diverse and active microbiocenosis, yet little is known about the occurrence and importance of, microbial metal(loid) methylation and hydrogenation. In the study, an in vitro gastrointestinal model, the Simulator of the Human Intestinal Microbial Ecosystem (SHIME), was used for investigating volatilization of metal(loid)s by intestinal microbiota. Suspensions from different compartments of the SHIME system analogous to different parts of the human intestinal tract were incubated with different concentrations of inorganic Ge, As, Se, Sri, Sb, Te, Hg, Pb, and Bi and analyzed by gas chromatography and inductively coupled plasma mass spectrometry (GC-ICP-MS). Significant volatilization was found for Se, As, and Te (maximal hourly production rates relative to the amount spiked; 0.6, 2, and 9 ng/mg/h, respectively). In addition, volatile species of Sb and Bi were detected. The occurrence of AsH(3) and (CH(3))(2)Te was toxicologically important. Furthermore, mixed Se/S and mixed As/S metabolites were detected in significant amounts in the gas phase of the incubation experiments of which two metabolites, (CH(3))(2)AsSSCH(3) and CH(3)As(SCH(3))(2), are described for the first time in environmental matrices. The toxicology of these species is unknown. These. data show that the intestinal microbiota may increase the mobility of metal(loid)s, suggesting a significant modulation of their toxicity. Our research warrant further studies to investigate the extent of this process as well as the availability of metal(loid)s from different sources for microbial transformations

Impact of systematic change of redox potential on the leaching of Ba, Cr, Sr, and V from a riverine soil into water

Floodplain soils are often contaminated with toxic elements such as Ba, Cr, Sr, and V. For an adequate risk assessment of such contaminated sites, the assessment of factors affecting the leaching of those elements from riverine soils into water is fundamental. Since the redox potential (E-H) can be important within this context, we aimed to assess the impact of pre-set redox conditions on the dynamics of Ba, Cr, Sr, and V in a floodplain soil. To achieve this aim, we used an automatic biogeochemical microcosm system allowing computer-controlled regulation of E-H by adapting the supply of N-2 or O-2 to the soil suspension. With this system, the effect of E-H on the dynamics of Ba, Cr, Sr, and V was studied mechanistically. Chromium and V were negatively correlated with E-H possibly due to co-precipitation of these metals with Fe (hydr)oxides at high E-H. Vanadium might additionally be oxidized from more soluble V(IV) to less soluble V(V) with rising E-H. Barium and Sr were positively correlated with E-H, which might be attributed to their association with dissolved organic carbon (DOC). The influence of pH on the dynamics of the studied elements seemed to be of minor importance in our study. A significant negative correlation was observed between the specific UV absorbance at 254 nm (SUVA (254)) and E-H indicating that oxidizing conditions favored the removal of aromatic DOC molecules from solution via binding to Fe (hydr)oxides. Redox potential is important for metal fate in the current study. Results imply an absorption of Cr and V to Fe (hydr)oxides and an interaction with DOC while particularly Ba and Sr dynamics may be influenced by DOC. In the future, different V species in wetland soils under pre-definite redox conditions should be determined and further studies should elucidate the specific role of DOC and sulfur (S) chemistry on the dynamics of the studied metals

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

Connection between Multimetal(loid) Methylation in Methanoarchaea and Central Intermediates of Methanogenesis▿†

In spite of the significant impact of biomethylation on the mobility and toxicity of metals and metalloids in the environment, little is known about the biological formation of these methylated metal(loid) compounds. While element-specific methyltransferases have been isolated for arsenic, the striking versatility of methanoarchaea to methylate numerous metal(loid)s, including rare elements like bismuth, is still not understood. Here, we demonstrate that the same metal(loid)s (arsenic, selenium, antimony, tellurium, and bismuth) that are methylated by Methanosarcina mazei in vivo are also methylated by in vitro assays with purified recombinant MtaA, a methyltransferase catalyzing the methyl transfer from methylcobalamin [CH3Cob(III)] to 2-mercaptoethanesulfonic acid (CoM) in methylotrophic methanogenesis. Detailed studies revealed that cob(I)alamin [Cob(I)], formed by MtaA-catalyzed demethylation of CH3Cob(III), is the causative agent for the multimetal(loid) methylation observed. Moreover, Cob(I) is also capable of metal(loid) hydride generation. Global transcriptome profiling of M. mazei cultures exposed to bismuth did not reveal induced methyltransferase systems but upregulated regeneration of methanogenic cofactors in the presence of bismuth. Thus, we conclude that the multimetal(loid) methylation in vivo is attributed to side reactions of CH3Cob(III) with reduced cofactors formed in methanogenesis. The close connection between metal(loid) methylation and methanogenesis explains the general capability of methanoarchaea to methylate metal(loid)s