Assessing the Role of the Gut Microbiome in Methylmercury Demethylation and Elimination in Humans and Gnotobiotic Mice Original paper

What was studied?

This study tested whether the gut microbiome helps the body clear dietary methylmercury (MeHg) by demethylating it into inorganic mercury (Hg(II)), which the intestine reabsorbs poorly and the body can excrete in stool. The researchers paired a controlled human fish-meal exposure protocol with mechanistic mouse experiments (conventional, antibiotic-treated, germ-free, and gnotobiotic/humanized models) and shotgun metagenomics of human stool. They also used anaerobic fecal cultures to measure how strongly each person’s stool community transformed mercury in vitro and compared that activity with each person’s MeHg elimination rate.

Who was studied?

The human arm enrolled adult volunteers (healthy, 18–80 years) who ate three tuna meals one week apart and then avoided fish for 60 days while researchers estimated MeHg elimination kinetics from mercury patterns along the hair shaft; 27–29 participants contributed usable datasets depending on analysis completeness, and MeHg half-lives spanned roughly 28–90 days. The animal arm used C57BL/6J mice to isolate microbiome effects by comparing intact microbiomes, microbiome depletion with antibiotics, complete absence of microbes in germ-free mice, and restoration via fecal microbiome transplant from selected human donors, plus a mono-colonization test with Alistipes onderdonkii.

What were the most important findings?

People varied widely in MeHg elimination, and faster elimination tracked with higher stool-community mercury transformation in anaerobic culture, supporting microbiome-driven demethylation as a key contributor to clearance. A prebiotic (inulin) reliably shifted microbiome composition but produced mixed elimination effects within individuals, arguing against a simple “more fiber equals faster clearance” rule. In mice, removing microbes (germ-free or antibiotics) sharply reduced stool Hg(II) and slowed elimination, while transplanting human stool microbiomes into germ-free mice restored faster elimination. Metagenomics did not detect canonical merB demethylation genes, pointing to a nontraditional pathway. As major microbial associations, Alistipes (especially Alistipes onderdonkii) correlated positively with faster human elimination, while Bacilli and two Lachnospiraceae-related OTUs correlated negatively; however, A. onderdonkii alone did not restore normal elimination in mono-colonized mice, implying a consortium effect or host–microbe interaction rather than a single “silver bullet” species.

What are the greatest implications of this study?

Clinically, this work strengthens the idea that gut microbiome function can shift MeHg body burden by changing how much MeHg gets demethylated in the gut and trapped for fecal loss, which may help explain why two people with similar fish exposure can carry very different risk. It also warns against oversimplified interventions: a prebiotic can remodel the microbiome yet still yield unpredictable MeHg clearance changes, so patient-specific microbial function matters more than broad taxonomic shifts. For a microbiome signatures database, the most actionable signal is functional—demethylation capacity—supported by taxa-level markers like Alistipes/Alistipes onderdonkii (positive) and certain Lachnospiraceae/Bacilli patterns (negative), while the missing merB signal suggests clinicians should not assume classic mercury-resistance genes drive gut demethylation in humans.