An engineered gut bacterium protects against dietary methylmercury exposure in pregnant mice.

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作者:Yu Kristie B, Chandra Franciscus, Coley-O'Rourke Elena J, Paulson Erik T, Novoselov Anna, Zhang David, Finnigan Delanie, Paramo Jorge, Lopez-Romero Arlene, Dong Tien S, Schartup Amina T, Hsiao Elaine Y
Despite efforts to decrease mercury emissions, chronic exposure to the neurotoxicant methylmercury (MeHg) continues to be a global problem that contributes to disparities in risk for neurological and metabolic diseases. Herein we engineer a human commensal gut bacterium, Bacteroides thetaiotaomicron (Bt), to detoxify MeHg by heterologous expression of organomercury lyase (MerB) and mercuric reductase (MerA) genes derived from a resistant bacterium isolated from Hg-polluted mines. We demonstrate that Bt(merA/B) demethylates MeHg both in vitro and within the intestines of mice orally exposed to MeHg or diets containing MeHg-rich fish. In pregnant mice exposed to dietary MeHg, Bt(merA/B) decreases MeHg accumulation in the maternal liver, brain, placenta, and fetal brain, and attenuates the expression of cellular stress genes in the fetal brain. Overall, this work provides foundational proof-of-principle supporting the ability of an engineered gut bacterium to limit MeHg bioaccumulation and reduce adverse effects of chronic MeHg exposure.

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