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, 5 (6), 491-504

The Human Gut Microbiome's Influence on Arsenic Toxicity

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The Human Gut Microbiome's Influence on Arsenic Toxicity

Michael Coryell et al. Curr Pharmacol Rep.

Abstract

Purpose of review: Arsenic exposure is a public health concern of global proportions with a high degree of interindividual variability in pathologic outcomes. Arsenic metabolism is a key factor underlying toxicity, and the primary purpose of this review is to summarize recent discoveries concerning the influence of the human gut microbiome on the metabolism, bioavailability, and toxicity of ingested arsenic. We review and discuss the current state of knowledge along with relevant methodologies for studying these phenomena.

Recent findings: Bacteria in the human gut can biochemically transform arsenic-containing compounds (arsenicals). Recent publications utilizing culture-based approaches combined with analytical biochemistry and molecular genetics have helped identify several arsenical transformations by bacteria that are at least possible in the human gut and are likely to mediate arsenic toxicity to the host. Other studies that directly incubate stool samples in vitro also demonstrate the gut microbiome's potential to alter arsenic speciation and bioavailability. In vivo disruption or elimination of the microbiome has been shown to influence toxicity and body burden of arsenic through altered excretion and biotransformation of arsenicals. Currently, few clinical or epidemiological studies have investigated relationships between the gut microbiome and arsenic-related health outcomes in humans, although current evidence provides strong rationale for this research in the future.

Summary: The human gut microbiome can metabolize arsenic and influence arsenical oxidation state, methylation status, thiolation status, bioavailability, and excretion. We discuss the strength of current evidence and propose that the microbiome be considered in future epidemiologic and toxicologic studies of human arsenic exposure.

Keywords: Arsenic; Human gut microbiome.

Conflict of interest statement

Conflicts of Interest The authors declare no conflicts of interest.

Figures

Fig. 1
Fig. 1
Overview of supported and potential arsenic-microbiome interactions in the mammalian gut. Bacteria-encoded enzymes (a dotted boxes, black text) are known to biotransform inorganic and organic arsenicals via reduction, oxidation, methylation, and demethylation reactions (a dotted boxes, blue text) in combination with requisite substrates (a dotted boxes, red text). Bacterial metabolites (a dotted box, green text) may also be important for arsenical biotransformation in the gut. Starting and end products in these biotransformations are labeled with arrows. While bacteria are known to drive all these reactions, evidence for demethylation and oxidation has yet to be generated for bacteria living in a mammalian gut and thiolation due to bacterial hydrogen sulfide (H2S) production has yet to be shown directly. The overall fate of arsenic in the gut (b) is influenced by the composition of intestinal contents and the likelihood of bacteria to sequester arsenic into biomass. These routes are similar to source-sink dynamics that take place in the environment.

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