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

Abstract

Arsenic (As) contamination in water or food is a global issue affecting hundreds of millions of people. Although As is classified as a group 1 carcinogen and is associated with multiple diseases, the individual susceptibility to As-related diseases is highly variable, such that a proportion of people exposed to As have higher risks of developing related disorders. Many factors have been found to be associated with As susceptibility. One of the main sources of the variability found in As susceptibility is the variation in the host genome, namely, polymorphisms of many genes involved in As transportation, biotransformation, oxidative stress response and DNA repair affect the susceptibility of an individual to As toxicity and then influence the disease outcomes. In addition, lifestyles and many nutritional factors, such as folate, vitamin C, and fruit, have been found to be associated with individual susceptibility to As-related diseases. Recently, the interactions between As exposure and the gut microbiome have been of particular concern. As exposure has been shown to perturb gut microbiome composition, and the gut microbiota has been shown to also influence As metabolism, which raises the question of whether the highly diverse gut microbiota contributes to As susceptibility. Here, we review the literature and summarize the factors, such as host genetics and nutritional status, that influence As susceptibility, and we also present potential mechanisms of how the gut microbiome may influence As metabolism and its toxic effects on the host to induce variations in As susceptibility. Challenges and future directions are also discussed to emphasize the importance of characterizing the specific role of these factors in inter-individual susceptibility to As-related diseases.

Evaluation of a Physiologically Based Pharmacokinetic (PBPK) Model for Inorganic Arsenic Exposure Using Data from Two Diverse Human Populations

“…Human exposures to arsenic are linked to a range of sources and exposure pathways, with individual intakes varying widely by location, employment, gender, age, and other characteristics that differ across individuals and populations ( Chi et al. 2018 ; Minatel et al.…”

Recent Advances in Arsenic Research: Significance of Differential Susceptibility and Sustainable Strategies for Mitigation

“…Majority of the affected population are exposed to arsenic primarily through drinking water and food. Several studies have described the mechanism of arsenic metabolism inside human biological system ( 15 – 17 ). The inorganic form of oxy-anions, including pentavalent arsenite (H 2 ) and trivalent arsenate (H 3 AsO 3 ) is present abundantly in natural water.…”

“…Another pathway of arsenic metabolism shows sequential addition of methyl groups to trivalent arsenicals and its conjugation with glutathione generating intermediate derivatives like arsenic triglutathione (ATG), monomethyl arsenic diglutathione (MADG), and dimethyl arsenic glutathione (DMAG). A third pathway explained about the formation of iAs/protein conjugate and subsequent generation of methylated metabolites ( 17 ). Various studies have also shown effect of folate intake and folate metabolism on arsenic metabolism and related disease risks.…”

Arsenic and the gastrointestinal tract microbiome

“…Chi et al . () review how human genetics, lifestyle and diet will influence individual susceptibility to As‐related diseases. We offer to continue this dialogue but explicitly from the perspective of the GIT microbiome.…”

“…Arsenic research in the GIT microbiome is in a relative state of infancy and can benefit from an early exchange of ideas, concepts and views. Chi et al (2018) review how human genetics, lifestyle and diet will influence individual susceptibility to As-related diseases. We offer to continue this dialogue but explicitly from the perspective of the GIT microbiome.…”