(P19-058-25) Gut Microbes Shape the Fate of Dietary Mercury

Objectives: Methylmercury (MeHg) is a persistent environmental toxin that bioaccumulates in higher trophic level predators, most notably in seafood, a key dietary protein source worldwide; however, exposure is unavoidable. While environmental microbes can bioremediate heavy metals, the relevance of these processes in the human gastrointestinal tract remains unclear. The objective of this study is to investigate how microbiome-metal interactions impact the bioavailability of dietary metals in the gut.

Methods: We first identified gut microbes harboring genes for organomercurial lyase (MerB) and mercuric reductase (MerA), enzymes that covert MeHg into less bioavailable forms using Hidden Markov Models. Leveraging ex vivo models, we investigated the impacts of MeHg on the composition of the human gut microbiome through 16S rRNA gene sequencing analysis. Given the rarity of MerB in the gut microbiome, we engineered probiotic Lacticaseibacillus strains via chromosomal integration and evaluated their bioremediation activity in vitro and in gnotobiotic mouse models to understand their impact on mercury bioavailability in the intestinal tract.

Results: Out of the 398 gut bacterial strains analyzed, only 5 contained the merB gene, and 1 strain possessed both merB and merA, further demonstrating the rarity and sporadic distribution of mercury biotransformation genes within the gut microbiome. In vitro bioremediation assays showed that Peptostreptococcus anaerobius harboring both merB and merA genes effectively reduced both MeHg and inorganic mercury (InHg) concentrations, suggesting significant detoxification potential. We observed interindividual variation in susceptibility to MeHg and shifts in microbial community composition associated with MeHg exposure. Functional analysis confirmed that chromosomal integration facilitated the intracellular accumulation of InHg in vitro. Interestingly, the bacterial strains possessing mer genes exhibited increased sensitivity to mercury exposure.

Conclusions: This work extends our understanding of how gut microbiota regulates metal bioavailability and demonstrates the potential of microbiome-targeted strategies to improve human nutrition and health.

Funding Sources: NIGMS (R35 GM151045) and Young Investigator Grant for Probiotics Research