Lu, K; Cable, PH; Abo, RP; Ru, H; Graffam, ME; Schlieper, KA; Parry, NMA; Levine, S; Bodnar, WM; Wishnok, JS; Styblo, M; Swenberg, JA; Fox, JG; Tannenbaum, SR
Exposure to arsenic affects large human populations worldwide, and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which are frequently associated with different patterns of arsenic metabolism. Several underlying mechanisms, such as genetic polymorphisms and epigenetics, have been proposed, as these factors closely impact the individuals' capacity to metabolize arsenic. In this context, the role of the gut microbiome in directly metabolizing arsenics and triggering systemic responses in diverse organs raises the possibility that perturbations of the gut microbial communities affect the spectrum of metabolized arsenic species and subsequent toxicological effects. In this study, we used an animal model with altered gut microbiome induced by bacterial infection, 16S rRNA gene sequencing and inductively coupled plasma mass spectrometry (ICP-MS)-based arsenic speciation to examine the effect of gut microbiome perturbations on the biotransformation of arsenic. Metagenomics sequencing revealed that bacterial infection significantly perturbed the gut microbiome composition in C57BL/6 mice, which in turn resulted in altered spectra of arsenic metabolites in urine, with inorganic arsenic species and methylated arsenics being up- and down-regulated, respectively. These data clearly illustrated that gut microbiome phenotypes significantly affected arsenic metabolic reactions, including reduction, methylation and thiolation. These findings improve our understanding of how infectious diseases and environmental exposure interact, and may also provide novel insight regarding the gut microbiome composition as a new risk factor of individual susceptibility to environmental chemicals.
