# Human microbiome metabolites in health and disease

> **NIH NIH R35** · HARVARD MEDICAL SCHOOL · 2020 · $423,750

## Abstract

Project Summary / Abstract
The human microbiome plays a vital role in health and disease. However, the ways in which the bacterial
guests interact with and affect the human host at a molecular level are poorly understood. One of the most
concrete effects that human-associated bacteria have on the host is to produce small molecule metabolites,
some of which accumulate in the body to levels higher than that of a typical drug. The long-term goal of my
laboratory is to understand and control the chemistry of human-associated bacteria in order to uncover how the
bacterial guests affect the human host in states of both health and disease. We are prioritizing the study of
bacterially produced metabolites from bioactive compound classes. These molecules contain conserved
structural elements and have potent biological activities in the human body. Although much is known about the
function of these molecules in host-self and host-pathogen interactions, less is known about how production or
modification of these compounds by commensal bacteria affects other bacteria and the human host. By
studying bioactive compound classes through a new lens, that of the human microbiome, we will uncover
crucial small molecule-mediated interactions underlying host health and disease.
Over the next five years, one major focus area of my laboratory will be to investigate the bacterial metabolism
of bile acids. These steroidal natural products constitute an important part of the molecular environment of a
healthy human gut. In the colon, bile acids are modified by the resident bacteria in near-quantitative fashion,
forming a class of roughly 50 different metabolites called secondary bile acids. Bile acids play crucial roles in
the host by acting both as detergents that aid in digestion and as ligands for host receptors, including FXR and
TGR5. These interactions suggest that modulation of bile acids represents a significant opportunity for
intervention in obesity and metabolic syndrome. However, the role of specific bile acids in the regulation of host
metabolism remains undefined, and as a result, the therapeutic potential of targeting bacterial bile acid
metabolism remains unexplored.
Previous studies involving bile acids have fallen mainly into two categories: (1) research focused on host
biology and (2) research focused on bacterial biochemistry. As a result, crucial connections between bacterial
biochemical transformations of bile acids and the in vivo function of these molecules have not yet been fully
established. By taking a chemically guided approach to understanding both the production and in vivo
functions of this class of bacterial 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 bile acid metabolism functions on a molecular level and how this activity
affects host physiology. Our research program will...

## Key facts

- **NIH application ID:** 9962902
- **Project number:** 5R35GM128618-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Abigail Sloan Devlin
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962902

## Citation

> US National Institutes of Health, RePORTER application 9962902, Human microbiome metabolites in health and disease (5R35GM128618-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9962902. Licensed CC0.

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