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Arsenic Metabolism by Human Gut Microbiota upon In Vitro Digestion of Contaminated Soils
Citation:
Van de Wiele, T., C. GALLAWA, K. KUBACHKA, JOHN T. CREED, N. T. BASTA, E. Dayton, S. Whitacre, G. Du Laing, AND K. D. BRADHAM. Arsenic Metabolism by Human Gut Microbiota upon In Vitro Digestion of Contaminated Soils. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 118(7):1004-1009, (2010).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
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 µg methylarsenical/g biomass/hr) and of As-contaminated soils (up to 28 µg/g biomass/hr). Besides the formation of monomethylarsonic acid (MMAv), we detected the highly toxic monomethyl-arsonous acid (MMAIII). Moreover, this is the first description of microbial thiolation leading to monomethylmonothioarsonic acid (MMMTAv). MMMTAv, 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.
URLs/Downloads:
Environmental Health Perspectives
Arsenic Metabolism by Human Gut Microbiota Upon In Vitro Digestion of Contaminated Soils (PDF, NA pp, 5249 KB, about PDF)