title: Gut microbiome perturbations induced by bacterial infection affect arsenic biotransformation.
abstract: 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 arsenic 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 an altered gut microbiome induced by bacterial infection, 16S rRNA gene sequencing, and inductively coupled plasma mass spectrometry-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 and thiolated arsenic being perturbed. 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.
authors.affiliation: Department of Biological Engineering, ‡Department of Biology, §Division of Comparative Medicine, and ∥Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States.
authors.forename: Kun
authors.initials: K
authors.lastname: Lu
authors.forename: Peter Hans
authors.initials: PH
authors.lastname: Cable
authors.forename: Ryan Phillip
authors.initials: RP
authors.lastname: Abo
authors.forename: Hongyu
authors.initials: H
authors.lastname: Ru
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Graffam
authors.forename: Katherine Ann
authors.initials: KA
authors.lastname: Schlieper
authors.forename: Nicola M A
authors.initials: NM
authors.lastname: Parry
authors.forename: Stuart
authors.initials: S
authors.lastname: Levine
authors.forename: Wanda M
authors.initials: WM
authors.lastname: Bodnar
authors.forename: John S
authors.initials: JS
authors.lastname: Wishnok
authors.forename: Miroslav
authors.initials: M
authors.lastname: Styblo
authors.forename: James A
authors.initials: JA
authors.lastname: Swenberg
authors.forename: James G
authors.initials: JG
authors.lastname: Fox
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tannenbaum
mesh_terms: D000818:Animals; D001151:Arsenic / Q000378:metabolism*; D004195:Disease Models, Animal; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology*; D016998:Helicobacter / Q000502:physiology*; D016481:Helicobacter Infections / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001151:Arsenic