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

Abstract

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.

Keywords: Bacteroides thetaiotaomicron; exposures; methylmercury; microbiome; neurodevelopment; neurotoxicant; pregnancy; synthetic biology.