# Microbial mechanisms of methylmercury metabolism in humans

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $538,053

## Abstract

Abstract
Mercury (Hg) continues to pose a significant risk to human health reflected by its #3 ranking on the U.S. Agency
of Toxic Substances and Disease Registry priority list of hazardous substances, behind only arsenic and lead.
Of greatest concern is exposure to the more toxic methylmercury (MeHg) that comes with eating fish. Four billion
people world-wide rely on fish as a significant source of dietary protein and essential nutrients. Thus, the
“mercury problem” cannot be solved by simply avoiding the major source of exposure. On the other hand, what
constitutes a harmful level of MeHg exposure remains considerably uncertain. For example, federal (US EPA)
guidelines for fish consumption are based on a Reference Dose (RfD) value for intake of MeHg, which
incorporates 10-fold “uncertainty factor”. It is known that much of this uncertainty stems from the fact that people
metabolize MeHg at widely variable rates and as a result two similarly sized individuals consuming equal
amounts of fish could experience as much as a four-fold difference in accumulated MeHg. A solution to this
problem lies in developing the knowledge and tools to determine an individual’s predisposition to accumulate
MeHg. Yet, several fundamental gaps in the knowledge of how the human body metabolizes and eliminates
MeHg remain. Prior research, largely in laboratory animals, supports the notion that microbes in the gut are
required for the efficient biotransformation (demethylation) and excretion of toxic MeHg. We have recently
obtained substantiating evidence that the rate of MeHg elimination in the human body is reliant on gut microbes.
Importantly, we discovered that MeHg elimination rate in a given individual can vary significantly over time and,
furthermore, is significantly slowed with exposure to antibiotics. With this evidence, we will test the hypothesis
that an individual’s susceptibility for reaching harmful levels of MeHg in the body is regulated by a select number
of microbes common to the human gut. We predict these microbes will be present in variable amounts in different
individuals, and thus could serve as a biomarker for MeHg metabolism disposition. We also predict a change in
abundance of these microbes can be achieved with a probiotic diet supplement. We will test our hypothesis in
a coordinated team effort involving experts in MeHg exposure and metabolism in humans, gut microbial ecology
in mouse models, and microbial Hg biotransformation and genomics. In three Specific Aims we will: establish
gut microbiome samples that exhibit “fast” and “slow” MeHg kinetics in humans (Aim1), validate the microbiome’s
role in MeHg kinetics using germ free mouse modeling (Aim2) and identify and isolate microbial species
responsible for MeHg demethylation in the human gut (Aim3). With knowledge from this study we intend to
improve human health practices by: 1) deriving non-invasive tools to identify individuals susceptible to
accumulating MeHg and 2) identifying dietary ...

## Key facts

- **NIH application ID:** 10240601
- **Project number:** 5R01ES030940-03
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** MATTHEW D RAND
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $538,053
- **Award type:** 5
- **Project period:** 2019-09-19 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240601

## Citation

> US National Institutes of Health, RePORTER application 10240601, Microbial mechanisms of methylmercury metabolism in humans (5R01ES030940-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240601. Licensed CC0.

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