Arsenic and the gastrointestinal tract microbiome

Abstract

Summary Arsenic is a toxin, ranking first on the Agency for Toxic Substances and Disease Registry and the Environmental Protection Agency Priority List of Hazardous Substances. Chronic exposure increases the risk of a broad range of human illnesses, most notably cancer; however, there is significant variability in arsenic‐induced disease among exposed individuals. Human genetics is a known component, but it alone cannot account for the large inter‐individual variability in the presentation of arsenicosis symptoms. Each part of the gastrointestinal tract (GIT) may be considered as a unique environment with characteristic pH, oxygen concentration, and microbiome. Given the well‐established arsenic redox transformation activities of microorganisms, it is reasonable to imagine how the GIT microbiome composition variability among individuals could play a significant role in determining the fate, mobility and toxicity of arsenic, whether inhaled or ingested. This is a relatively new field of research that would benefit from early dialogue aimed at summarizing what is known and identifying reasonable research targets and concepts. Herein, we strive to initiate this dialogue by reviewing known aspects of microbe–arsenic interactions and placing it in the context of potential for influencing host exposure and health risks. We finish by considering future experimental approaches that might be of value.

Introducing the ArsR-Regulated Arsenic Stimulon

“…Initial work examining the impact of arsenic on the gut microbiome has clearly established that there are numerous and significant effects, but thus far the basis for these effects is unknown. An initial fate of ingested arsenic is to interact with the gastrointestinal tract microbiome wherein numerous transformations are possible (Coryell et al, 2018;McDermott et al, 2019) and that will have consequences for the host as well as other microbiome members (McDermott et al, 2019). Initial work examining the impact of arsenic on the gut microbiome have clearly established that there are numerous and significant effects, including altered microbiome structure and composition as well as metabolomic profiles (Lu et al, 2014;Chi et al, 2017Chi et al, , 2019aLiu et al, 2019); however, thus far the basis for these changes is unknown.…”

“…Initial work examining the impact of arsenic on the gut microbiome have clearly established that there are numerous and significant effects, including altered microbiome structure and composition as well as metabolomic profiles (Lu et al, 2014;Chi et al, 2017Chi et al, , 2019aLiu et al, 2019); however, thus far the basis for these changes is unknown. The ars genes/operons of Gram-positive and Gram-negative organisms are quite common in the human gut microbiome (McDermott et al, 2019), and there is no reason to view their transcriptional control to be any different to that shown in numerous pure culture isolates from virtually every other environment. Now, in addition to the specific ars-encoded functions, the very extensive profile of functions influenced by the ArsR protein documented herein offers a qualitative indication of what might be expected in the human gut microbiome and assists in explaining the very significant microbiome metabolic changes observed in different mouse studies (Lu et al, 2013;Guo et al, 2014;Lu et al, 2014;Richardson et al, 2018;Chi et al, 2019c;Liu et al, 2019).…”

“…Consequently, understanding how and why microbes react to As in their environment is important with respect to issues involving land resource management (Inskeep et al, 2002), as well as human medicine (i.e. gastrointestinal tract) (Coryell et al, 2018;McDermott et al, 2019).…”

Microbial Oxidation of Arsenite: Regulation, Chemotaxis, Phosphate Metabolism and Energy Generation

“…Arsenic (As) is a ubiquitous metalloid in the environment, and it belongs to group 15 in the periodic table, positioned directly below phosphorus (Strawn, 2018). Arsenic exists in various forms, such as inorganic trivalent arsenite [As(III)], inorganic pentavalent arsenate [As(V)], trivalent organoarsenicals, pentavalent organoarsenicals and thioarsenicals (Chen J. et al, 2015;McDermott et al, 2020). Of which, As(III) and As(V) are the most prevalent forms (Zhu et al, 2014).…”

The Need to Unravel Arsenolipid Transformations in Humans

“…2.4). Reproducing these results with a higher number of individuals is crucial, especially considering the variability of arsenic metabolism in humans (Jakobsson et al , 2015 ), not only due to physiological and genetic factors (Tseng, 2009 ) but also due to gut microbial differences (McDermott et al , 2020 ).…”