# Human microbiome metabolites in health and disease

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2024 · $435,435

## Abstract

Project Summary / Abstract
The human microbiome plays a vital role in health and disease. However, the ways in which bacteria affect the
human host at a molecular level remain poorly understood. In order to harness connections between the
microbiome and disease to improve human health, we need to know more about the molecules and chemical
mechanisms driving host-microbiota interactions. The long-term goal of my laboratory is to understand and
control the chemistry of human-associated bacteria in order to uncover how the microbiome affects human health
and disease.
We are prioritizing the study of human gut bacterial metabolism of host-produced small molecules (endobiotics)
and how the resultant compounds affect host physiology. Endobiotics such as steroids and vitamins act as crucial
signaling molecules and regulators of host biology, but their metabolism by gut bacteria has been relatively
unexplored. We aim to uncover the biosynthetic pathways and biological roles of host-produced, bacterially
modified metabolites. We are also expanding the scope of our studies of microbiome metabolites to study novel
transformations of host- and diet-derived metabolites by microbiome bacteria and how these metabolites affect
the host.
With the support of an NIH ESI MIRA grant, my group has established a track record of discovering gut microbial
metabolites of bile acids, elucidating how these compounds are biosynthesized, and determining the effects of
these compounds on the host. We have demonstrated that we can advance microbiome research from molecule
discovery to in vivo effects. These studies have allowed us to establish a roadmap for the proposed studies
investigating microbiome metabolites more broadly. Over the next five years, we will (1) discover new chemical
transformations by human-associated bacteria that lead to bioactive metabolites, (2) investigate the effects of
microbiome metabolites on host physiology, including host immune response, metabolism, and neurological
function and behavior, and (3) identify active enzymes responsible for keystone microbiome transformations
using comparative metabolomics and chemoproteomics. By taking a chemically guided approach to
understanding both the production and in vivo functions of microbiome metabolites, we will gain a more complete
understanding of these molecules and their biological activities than has ever been established. This work will
provide us with a deeper understanding of how gut bacterial metabolism of host- and diet-derived compounds
functions on a molecular level and how this activity affects host physiology. Our research program will also lay
the groundwork for the rational manipulation of the microbiome in a clinical context to treat disease and improve
health.

## Key facts

- **NIH application ID:** 10842312
- **Project number:** 5R35GM128618-07
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Abigail Sloan Devlin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $435,435
- **Award type:** 5
- **Project period:** 2018-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842312

## Citation

> US National Institutes of Health, RePORTER application 10842312, Human microbiome metabolites in health and disease (5R35GM128618-07). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10842312. Licensed CC0.

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