Preabsorptive Metabolism of Sodium Arsenate by Anaerobic Microbiota of Mouse Cecum Forms a Variety of Methylated and Thiolated Arsenicals

Abstract
The conventional scheme for arsenic methylation accounts for methylated oxyarsenical production but not for thioarsenical formation. Here, we report that in vitro anaerobic microbiota of mouse cecum converts arsenate into oxy- and thio- arsenicals. Besides methylarsonic acid (MMA(V)), arsenate was transformed into six unique metabolites: mono-, di-, and trithio-arsenic acid, monomethyldithio- and monomethyltrithio-arsonic acid, and dimethyldithioarsonic acid. Thioarsenicals were found in soluble and particulate fractions of reaction mixtures, suggesting interactions with anaerobic microbiota. Metabolism of ingested arsenate to oxy- and thio-arsenicals before absorption across the gastrointestinal barrier could affect bioavailability, systemic distribution, and resulting toxicity.