Dietary Arsenic and Gut Microbiome Analysis

Abstract

BACKGROUNDTypical exposure to inorganic arsenic (iAs) in food and water is linked to cancers, toxicity, and other health effects. The extent to which dietary iAs is metabolized to mono and dimethyl arsenicals (MMA and DMA) affects toxicity. Nutritional, genetic, and other factors determine iAs methylation, but recent experiments show that the gut microbiome also plays a role. In turn, iAs alters the composition of gut microbiota in mice. We evaluated the relationship of dietary iAs exposure to changes in gut microbiota in humans and mice and potential effects of gut microbiota on iAs methylation and toxicity.METHODSUsing a cross‐over design, a controlled dietary intervention study was conducted in human subjects and mice. Human subjects consumed a low‐As diet for 6 days, followed by 5 days on a high‐iAs diet that consisted of 3 servings per day of commercial rice products (110–250 μg/kg As). After establishing a baseline, mice were fed high‐iAs chow (138 μg/kg As) for 3 weeks, then low‐As chow (14 μg/kg As) for 1 week. Urine, blood, and stool samples were collected during and after each phase and samples were analyzed for total As and iAs metabolites. Fecal microbiota was analyzed using 16S rRNA amplicon profiling.RESULTSIn humans, high‐As diet was generally associated with an increase in Bacteroidaceae (from 40 to 54%) and decrease in Lachnospiraceae family from 25% to 18%. The high‐As diet resulted in a doubling of urinary As metabolites. Compared to the middle tertile of the urinary %DMA (DMA/sum of As metabolites), subjects in the highest tertile showed an increase in Bacteroidaceae (26% vs 51%) and decreases in Lachnospiraceae (26% vs 20%) and Ruminococcaceae (25% vs 15%). Those changes were correlated with the middle, not the highest tertile of total blood As. Alpha‐diversity increased on the high vs. low‐As diet in the highest tertile of blood total As. There were, however, no significant differences in Principal Coordinate Analysis (PCoA) analysis by diet or blood As. In mice fed high‐As chow, Bacteroidales S24‐7 group increased 1.54‐fold and Bacteroidaceae decreased 0.82‐fold. The highest vs. lowest tertile of %DMA was associated with a 1.4‐fold increase in Bacteroidales S24‐7 group bacteria in the mouse gut and decreases in most of the other major taxa. Contrary to human subjects, alpha diversity it was higher in mice fed low‐As chow, particularly in the highest tertile of urinary iAs excretion. The mouse microbiome showed a clear separation between mice on low‐ vs. high‐As chow in PCoA plots. The composition of bacterial flora in the guts of humans and mice overlapped, but relative abundances differed. Human subjects showed an increase in Bacteroidaceae during the high‐As diet, while in mice, Bacteroidaceae decreased sharply.CONCLUSIONThis is a preliminary assessment of the effects of dietary iAs on the mouse and human gut microbiome. High secondary methylation capacity (i.e., high %DMA) was associated with a large increase in the prevalence of Bacteroidaceae in the human gut and a large increase in Bacteroidales S24‐7 group in the mouse gut. The impact of alterations in gut microflora will require further investigation.Support or Funding InformationResearch Support: University of Arizona, Southwest Environmental Health Science Center (SWEHSC) Grant Number – P30 ES006694This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.