The gut microbiome promotes arsenic metabolism and alleviates the metabolic disorder for their mammal host under arsenic exposure

Abstract

Gut microbiome can participate in arsenic metabolism. However, its efficacy in the host under arsenic stress is still controversial. To clarify their roles in fecal arsenic excretion, tissue arsenic accumulation, host physiological states and metabolism, in this study, ninety-six C57BL/6 male mice were randomly divided to four groups, groups A and B were given sterile water, and groups C and D were given the third generation of broad-spectrum antibiotic (ceftriaxone) to erase the background gut microbiome. Subsequently, groups B and D were subchronicly exposed to arsenic containing feed prepared by adding arsenical mixture (rice arsenic composition) into control feed. In group D, the fecal total arsenic (C_tAs) decreased by 25.5 %, iAs^III composition increased by 46.9 %, unclarified As (uAs) composition decreased by 92.4 %, and the liver C_tAs increased by 26.7 %; the fecal C_tAs was positively correlated with microbial richness and some metabolites (organic acids, amino acids, carbohydrates, SCFAs, hydrophilic bile acids and their derivatives); and fecal DMA was positively correlated with microbial richness and some metabolites (ferulic acid, benzenepropanoic acid and pentanoic acid); network analysis showed that the numbers of modules, nodes, links were decreased and vulnerability was increased; some SCFAs and hydrophilic bile acid decreased, and hydrophobic bile acids increased (Ps < 0.05). In the tissue samples of group D, Il-18 and Ifn-γ gene expression increased and intestinal barrier-related genes Muc2, Occludin and Zo-1 expression decreased (Ps < 0.05); serum glutathione and urine malondialdehyde significantly increased (Ps < 0.05); urine metabolome significantly changed and the variation was correlated with six SCFAs-producing bacteria, and some SCFAs including isobutyric acid, valeric acid and heptanoic acid decreased (Ps < 0.05). Therefore, the normal gut microbiome increases fecal arsenic excretion and biotransformation, which can maintain a healthier microbiome and metabolic functions, and alleviate the metabolic disorder for their mammal host under arsenic exposure.

Keywords: Arsenic biotransformation; Ceftriaxone; Gut microbiome; Metabolomics; Rice arsenicals.