Arsenic Thiolation and the Role of Sulfate-Reducing Bacteria from the Human Intestinal Tract

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.Citation: DC.Rubin SS, Alava P, Zekker I, Du Laing G, Van de Wiele T. 2014. Arsenic thiolation and the role of sulfate-reducing bacteria from the human intestinal tract. Environ Health Perspect 122:817–822; http://dx.doi.org/10.1289/ehp.1307759

In Vitro Method To Assess Soil Arsenic Metabolism by Human Gut Microbiota: Arsenic Speciation and Distribution

“…Furthermore, H 2 S as a sulfide source can induce As thiolation by sulfate-reducing bacteria from the human intestinal tract. 34 Although As metabolism by human gut microbiota was previously reported, 10,17,34 this is the first study to report As metabolism by gut microbiota from Chinese people with a high degree of reduction and methylation.…”

“…42 However, a large fraction of soil-bound As can end up in the colon, where an abundant microbial community resides, and methylation and thiolation by human gut microbiota have been found previously in the colon phase. 10,34 Studies have indicated that MMA V can be regarded as an intermediate in the production of MMMTA V by microbial thiolation; MMA V can even be reduced to highly toxic MMA III under the strongly reducing conditions of SHIME. Furthermore, H 2 S as a sulfide source can induce As thiolation by sulfate-reducing bacteria from the human intestinal tract.…”

“…MMMTA V was synthesized using a mixture of MMA V and H 2 S solutions by this method. 10,34 The sum of As species in the filtrate (0.45 μm) observed chromatographically was considered the bioaccessible As. In addition, the chromatographic recovery by this method was validated, 5 and the recovery of 1 NIST reference material (2710a) was 98.2%.…”

Variability of arsenic bioaccessibility and metabolism in soils by human gut microbiota using different in vitro methods combined with SHIME

“…Arsenic methylation and thiolation by human gut microbiota have been found previously in SHIME experiments (Rubin et al, 2014;Van de Wiele et al, 2010). Studies have indicated that MMA V can be regarded as an intermediate in the production of MMMTA V by microbial thiolation whose main sulfide source can be H 2 S by sulfate-reducing bacteria (SRB) (Rubin et al, 2014). The disparity in As methylation can be attributed to the impacts of different organic constituents for these methods.…”

“…As species in the colon digests were identified by comparing their retention times with those of standards [As(III), As(V), DMA V , MMA V and MMMTA V ] as quantified by external calibration curves with peak areas. MMMTA V was synthesized using a mixture of MMA V and H 2 S solutions by this method Rubin et al, 2014). 100 mL of saturated H 2 S solution was added to 900 mL of a 40 mg As mL − 1 MMA V solution in a glass vial.…”