Influence of pregnancy and the gut microbiome on methylmercury metabolism and elimination in the mother and fetus

. The developing fetus is exceptionally vulnerable to chemicals in the environment. Prenatal exposure to environmental contaminants, such as heavy metals, PFAS compounds and pesticides, impose a substantial societal cost due to the intellectual disability burden to children exposed early in life. Adverse chemical exposures are unavoidable in many cases, due to contaminated environments or the co-exposure that come with foodstuffs and with contaminated drinking water. Therefore, understanding how maternal handling of toxicant exposure, and particularly how the pregnant state may enhance or compromise this function, are a top priority. Mercury (Hg) is among the top environmental contaminants that pose human health risks, ranking third on the U.S. Agency of Toxic Substances Disease Registry priority list of hazardous substances. Methylmercury (MeHg) is the most highly toxic form of mercury and is commonly consumed with fish where it ultimately poses its greatest health risk to the developing fetus. In this proposal we investigate the potential impact of pregnancy on moderating MeHg clearance kinetics in the mother and thus, toxicity for the fetus. We will expand upon exciting and unexpected preliminary evidence that as pregnancy progresses, maternal elimination of MeHg increases, potentially reducing the exposure to the fetus. By optimizing tools that we have previously developed to monitor MeHg metabolism and excretion in non-pregnant adults, we will now evaluate pregnant women, who choose to eat fish routinely, for changes in MeHg elimination over time. With prior knowledge that the gut microbiome is responsible for MeHg metabolism (demethylation) that promotes its faster excretion, we will evaluate the maternal gut microbiome for demethylation activity in parallel. In addition, we will perform metagenomic sequencing to resolve the entirety of species in the gut microbiome to attempt to identify the organisms responsible for faster elimination. Finally, we will compare the mother’s MeHg elimination rate to that the fetus in third trimester. We anticipate the outcomes of this study will determine whether or not: 1) increased MeHg elimination with the progression of pregnancy is generalizable to all mothers, 2) the gut microbiome is a potential mediator of pregnancy-induced MeHg elimination and 3) fetal elimination of MeHg is entirely dictated by the mother or is moderated in part by the fetus itself. We view this as a high-risk, high-reward study, with great potential to reveal generalizable traits of the maternal microbiome that can limit toxicant exposures and furthermore be accessible to modifications that will ultimately reduce toxicity risk to the fetus. Project Number: 1R21ES037489-01A1 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Environmental Health Sciences (NIEHS) | Principal Investigator: MATTHEW RAND | Institution: UNIVERSITY OF ROCHESTER, ROCHESTER, NY | Award Amount: $415,613 | Activity Code: R21 | Study Section: Special Emphasis Panel[ZRG1 EMS-W (08)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11302365