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Environ Health Perspect. 2014 Aug;122(8):817-22. doi: 10.1289/ehp.1307759. Epub 2014 May 9.

Arsenic thiolation and the role of sulfate-reducing bacteria from the human intestinal tract.

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  • 1Laboratorium voor Microbiële Ecologie en Technologie, Faculteit Bio-ingenieurswetenschappen, Universiteit Gent, Gent, Belgium.

Abstract

BACKGROUND:

Arsenic (As) toxicity is primarily based on its chemical speciation. Although inorganic and methylated As species are well characterized in terms of metabolism and formation in the human body, the origin of thiolated methylarsenicals is still unclear.

OBJECTIVES:

We sought to determine whether sulfate-reducing bacteria (SRB) from the human gut are actively involved in the thiolation of monomethylarsonic acid (MMAV).

METHODS:

We incubated human fecal and colon microbiota in a batch incubator and in a dynamic gut simulator with a dose of 0.5 mg MMAV in the absence or presence of sodium molybdate, an SRB inhibitor. We monitored the conversion of MMAV into monomethyl monothioarsonate (MMMTAV) and other As species by high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry analysis. We monitored the sulfate-reducing activity of the SRB by measuring hydrogen sulfide (H2S) production. We used molecular analysis to determine the dominant species of SRB responsible for As thiolation.

RESULTS:

In the absence of sodium molybdate, the SRB activity-primarily derived from Desulfovibrio desulfuricans (piger)-was specifically and proportionally correlated (p < 0.01) to MMAV conversion into MMMTAV. Inactivating the SRB with molybdate did not result in MMAV thiolation; however, we observed that the microbiota from a dynamic gut simulator were capable of demethylating 4% of the incubated MMAV into arsenous acid (iAsIII), the trivalent and more toxic form of arsenic acid (iAsV).

CONCLUSION:

We found that SRB of human gastrointestinal origin, through their ability to produce H2S, were necessary and sufficient to induce As thiolation. The toxicological consequences of this microbial As speciation change are not yet clear. However, given the efficient epithelial absorption of thiolated methylarsenicals, we conclude that the gut microbiome-and SRB activity in particular-should be incorporated into toxicokinetic analysis carried out after As exposure.

PMID:
24833621
PMCID:
PMC4123032
DOI:
10.1289/ehp.1307759
[PubMed - indexed for MEDLINE]
Free PMC Article
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