Arsenic metabolism by human gut microbiota upon in vitro digestion of contaminated soils

Abstract

Background: Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. However, it is unclear whether human microbiota display similar As metabolism, especially when present in a contaminated matrix.

Objectives: We evaluated the metabolic potency of in vitro cultured human colon microbiota toward inorganic As (iAs) and As-contaminated soils.

Methods: A colon microbial community was cultured in a dynamic model of the human gut. These colon microbiota were incubated with iAs and with As-contaminated urban soils. We determined As speciation analysis using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry.

Results: We found a high degree of methylation for colon digests both of iAs (10 microg methylarsenical/g biomass/hr) and of As-contaminated soils (up to 28 microg/g biomass/hr). Besides the formation of monomethylarsonic acid (MMA(V)), we detected the highly toxic monomethylarsonous acid (MMA(III)). Moreover, this is the first description of microbial thiolation leading to monomethylmonothioarsonic acid (MMMTA(V)). MMMTA(V), the toxicokinetic properties of which are not well known, was in many cases a major metabolite.

Conclusions: Presystemic As metabolism is a significant process in the human body. Toxicokinetic studies aiming to completely elucidate the As metabolic pathway would therefore benefit from incorporating the metabolic potency of human gut microbiota. This will result in more accurate risk characterization associated with As exposures.

Figure 1

Identification of MMMTA^V by HPLC/ESI-MS/MS and HPLC/ICP-MS (left) [using separation 2; see Supplemental Material (doi:10.1289/ehp.0901794)]. The gray and black traces in chromatograms represent analysis of a soil extract and MMMTA^V standard, respectively. Right: MS/MS spectra of m/z 155 within each MS spectra.

Figure 2

Concentration (mean ± SD) of chromatographically detected As species in colon digests of iAs^V (225 μg/L) and of As-contaminated soils 1–4 (n = 3). Note the different scales for the As concentrations (y-axis) for iAs^V and contaminated soils.