The gut microbiome and arsenic-induced disease-iAs metabolism in mice

Abstract

Purpose of review: This review summarizes inorganic arsenic (iAs) metabolism and toxicity in mice and the gut microbiome and how iAs and the gut microbiome interact to induce diseases.

Recent findings: Recently, a variety of studies have started to reveal the interactions between iAs and the gut microbiome. Evidence shows that gut bacteria can influence iAs biotransformation and disease risks. The gut microbiome can directly metabolize iAs, and it can also indirectly be involved in iAs metabolism through the host, such as altering iAs absorption, cofactors, and genes related to iAs metabolism. Many factors, such as iAs metabolism influenced by the gut microbiome, and microbiome metabolites perturbed by iAs can lead to different disease risks. iAs is a widespread toxic metalloid in environment, and iAs toxicity has become a global health issue. iAs is subject to metabolic reactions after entering the host body, including methylation, demethylation, oxidation, reduction, and thiolation. Different arsenic species, including trivalent and pentavalent forms and inorganic and organic forms, determine their toxicity. iAs poisoning is predominately caused by contaminated drinking water and food, and chronic arsenic toxicity can cause various diseases. Therefore, studies of iAs metabolism are important for understanding iAs associated disease risks.

Keywords: Arsenic metabolism; Arsenic toxicity; Arsenic-induced disease; Gut microbiome.

Fig. 1

Three proposed iAs metabolism pathways. (GSTOs, GSH-S-transferase Omegas; PNP, purine nucleoside phosphorylase; GSH, glutathione; SAM, S-adenosylmethionine; As3MT, As methyltransferase; Trx, thioredoxin.). a Challenger pathway. Substrates were trivalent forms, and the products were pentavalent forms. b Hayakawa pathway. Substrates and products were trivalent forms throughout the metabolism processes. c Dheeman pathway. Oxidative methylation and reductions can undergo in this pathway and products are the more trivalent forms

Fig. 2

Pathways of iAs metabolism in bacteria. (ArrAB, respiratory arsenate reductase; AioAB, arsenite oxidase; Pit, low affinity phosphate inorganic transport system; Pst, high affinity phosphate-specific transport system; GlpF, glycerol facilitator; ArsC, arsenate reductase; ArsH, organoarsenical oxidase; ArsI, C–As bond lyases; ArsM, arsenite S-adenosylmethionine methyltransferase; ArsAB/Acr3/ArsK, arsenite efflux enzymes; ArsP, methylarsenite efflux enzymes; SRB, sulfate-reducing bacteria; H₂S, hydrogen sulfide)