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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.

SUBMITTER: D C Rubin SS

PROVIDER: S-EPMC4123032 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

D C Rubin Sergio S C SS Alava Pradeep P Zekker Ivar I Du Laing Gijs G Van de Wiele Tom T

Environmental health perspectives 20140509 8

<h4>Background</h4>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.<h4>Objectives</h4>We sought to determine whether sulfate-reducing bacteria (SRB) from the human gut are actively involved in the thiolation of monomethylarsonic acid (MMAV).<h4>Methods</h4>We incubated human fecal and colon micro ...[more]

PMID: 24833621

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Project description:BACKGROUND:Inflammatory bowel diseases (IBDs) are multifactorial illnesses of the intestine, to which microorganisms are contributing. Among the contributing microorganisms, sulfate-reducing bacteria (SRB) are suggested to be involved in the process of bowel inflammation due to the production of hydrogen sulfide (H2S) by dissimilatory sulfate reduction. The aims of our research were to physiologically examine SRB in fecal samples of patients with IBD and a control group, their identification, the study of the process of dissimilatory sulfate reduction (sulfate consumption and H2S production) and biomass accumulation. Determination of biogenic elements of the SRB and evaluation of obtained parameters by using statistical methods were also included in the research. The material for the research consisted of 14 fecal samples, which was obtained from patients and control subjects. METHODS:Microscopic techniques, microbiological, biochemical, biophysical methods and statistical analysis were included. RESULTS:Colonies of SRB were isolated from all the fecal samples, and subsequently, 35 strains were obtained. Vibrio-shaped cells stained Gram-negative were dominant in all purified studied strains. All strains had a high percentage of similarity by the 16S rRNA gene with deposited sequences in GenBank of Desulfovibrio vulgaris. Cluster analysis of sulfate reduction parameters allowed the grouping of SRB strains. Significant (p < 0.05) differences were not observed between healthy individuals and patients with IBD with regard to sulfate reduction parameters (sulfate consumption, H2S and biomass accumulation). Moreover, we found that manganese and iron contents in the cell extracts are higher among healthy individuals in comparison to unhealthy individuals that have an intestinal bowel disease, especially ulcerative colitis. CONCLUSIONS:The observations obtained from studying SRB emphasize differences in the intestinal microbial processes of healthy and unhealthy people.

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

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

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