The Effects of an Environmentally Relevant Level of Arsenic on the Gut Microbiome and Its Functional Metagenome

Abstract

Multiple environmental factors induce dysbiosis in the gut microbiome and cause a variety of human diseases. Previously, we have first demonstrated that arsenic alters the composition of the gut microbiome. However, the functional impact of arsenic on the gut microbiome has not been adequately assessed, particularly at environmentally relevant concentrations. In this study, we used 16S rRNA sequencing and metagenomics sequencing to investigate how exposure to 100 ppb arsenic for 13 weeks alters the composition and functional capacity of the gut microbiome in mice. Arsenic exposure altered the alpha and beta diversities as well as the composition profile of the gut microbiota. Metagenomics data revealed that the abundances of genes involved in carbohydrate metabolism, especially pyruvate fermentation, short-chain fatty acid synthesis, and starch utilization, and were significantly changed. Moreover, lipopolysaccharide biosynthesis genes, multiple stress response genes, and DNA repair genes were significantly increased in the gut microbiome of arsenic-exposed mice. The genes involved in the production or processing of multiple vitamins, including folic acid and vitamins B6, B12, and K2, were also enriched in arsenic-treated mice. In, addition, genes involved in multidrug resistance and conjugative transposon proteins were highly increased after treatment with arsenic. In conclusion, we demonstrate that arsenic exposure, at an environmentally relevant dose, not only perturbed the communal composition of the gut microbiome but also profoundly altered a variety of important bacterial functional pathways.

Long-term metal exposure changes gut microbiota of residents surrounding a mining and smelting area

“…The present study provides novel evidence that long-term exposure to multiple metals including As, Cd, Cu, Pb, and Zn is associated with alterations in the gut microbiome of people living in metal-polluted areas, especially for men. www.nature.com/scientificreports www.nature.com/scientificreports/ Metals such as As, Cd, and Cu, as well as excessive amounts of Zn, have been proven to reduce community diversity in previous studies 23,33,34 . Although no effect on α-diversity has been found, Pb was shown to change complexity (β-diversity) in an animal study 35 .…”

Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on Intestinal Microbiota and Gut-Associated Immune Status

“…Mice exposed for 2, 5, or 10 weeks to 0, 10, or 250 ppb arsenite (As III ) showed changes in the colonic microbial population, metabolic phenotype, and levels of metabolites in the tissue and serum (37). Another study showed that 100 ppb arsenic exposure for 13 weeks changed the gut microbial composition and altered important microbial functional pathways (carbohydrate metabolism [especially pyruvate fermentation], short-chain fatty acid synthesis, and starch utilization) that could influence host metabolism (38). Moreover, child gut microbiota exhibit high levels of As III , the more toxic form of arsenic, which could result in increased health risk (39).…”

Individual susceptibility to arsenic-induced diseases: the role of host genetics, nutritional status, and the gut microbiome

“…As we mentioned previously, previous studies indicated that increasing the intake of folate, riboflavin and cobalamin could protect people from As-induced diseases, which is related to As susceptibility [90, 91]. Our recent study found that in the low As-exposed gut microbiome, vitamin synthetic genes were largely enriched, suggesting a potential protective response to As exposure [130]. Likewise, choline is an essential nutrient and can be transformed into betaine to remethylate homocysteine in the one-carbon metabolism pathway [149].…”

“…First, accumulating evidence indicates that gut microbiota activities influence the bioaccessibility and biotransformation of As, which could influence the toxic effects of As on the host body [128, 129]. Second, studies show that As exposure can perturb the normal composition and functional gene profile of the gut microbiome and thus could potentially affect host health [10, 130]. As such, both of these aspects could influence the individual susceptibility to As-induced diseases.…”