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.

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

“…The authors suggest that the high cellular toxicity induced by arsenolipids may be related to their ability to easily pass cell membranes, possibly by passive diffusion. Thio-arsenicals are probably produced by the colon microbiota [95][96][97], and one recent study found that sulfatereducing bacteria present in the human gut was necessary for conversion of MA (V) into the thiolated monomethyl monothioarsonate [98]. Thio-arsenicals have been recognized as toxic in studies on human cells [132,133].…”

“…It is also possible that the microbiome of the GI-tract can play a role in the (pre-absorptive) metabolism of arsenicals. In vitro studies have shown that the microbiome in mouse coecum and human colon microbiota converts As (V) and methylated arsenicals into oxo-arsenicals and thio-arsenicals [95][96][97][98]. In our previous study, a multitude of urinary arsenicals excreted after volunteers ingested an identical meal consisting of 150 g blue mussels were identified;…”

The Gut Microbiota as Target for Innovative Drug Development: Perspectives and a Case Study of Inflammatory Bowel Diseases

“…This was demonstrated by the finding of significant volatilization of arsenic (As), selenium (Se), bismuth (Bi), tellurium (Te), and antimony; the formation of highly toxic AsH 3 (arsine) and (CH3) 2 Te (dimethyl telluride); and the discovery of two new As-sulfur metabolites. Van de Wiele et al (2010) and Pinyayev et al (2011) later showed the contribution of the gut microbiota, presumable sulfate reducers, in the formation of methylated thioarsenicals from which the toxicity is thought to be equivalent to that of trivalent inorganic arsenic.…”

Extracellular matrix proteins and the liver-lung axis in disease.

“…For instance, Pinyayev et al showed that bacteria from the mouse cecum can metabolize arsenic (141) and others have shown that the human gut flora can metabolize arsenic into toxic metabolites (142,143). Whereas this is distinctly possible, it should be noted that concentrations that are 10-fold higher than used here were not directly hepatotoxic (47).…”

“…In vitro studies have also shown that the bacteria of both the mouse and human gut can metabolize arsenic in vitro (141)(142)(143) . Such findings suggest that dysbiosis caused by HFD could cause dramatic changes in arsenic metabolism.…”