# Elucidating the role of an immunomodulator from a gut microbe in inflammatory bowel disease

> **NIH NIH F32** · HARVARD MEDICAL SCHOOL · 2020 · $67,446

## Abstract

Project Summary/Abstract
Inflammatory bowel disease (IBD) is an autoimmune disease that affects the digestive tract. It is strongly
correlated with imbalances in members of the gut microbial community. It is not known if the absence or
presence of specific microbes contributes to the progression of IBD. Monocultures of gut microbes strongly
associated with health or IBD were screened for their ability to produce molecules that are recognized by the
immune system to promote inflammation (by inducing TNFα) or to suppress inflammation (by inducing IL10).
From this screen, Ruminococcus gnavus was found to produce a potent anti-inflammatory molecule. This work
will identify and characterize this anti-inflammatory molecule, determine how it is made, how it is recognized by
the immune system, and whether it is present in clinical samples.
First, the anti-inflammatory molecule from R. gnavus will be purified from scale-up cultures with activity-guided
fractionation. Once pure, the structure will be determined using a combination of NMR, MS and X-ray
diffraction. To determine the distribution of the anti-inflammatory molecule and potential analogs among other
gut microbes the biosynthetic genes will be determined through gene deletion in R. gnavus, or heterologous
expression of genes of interest. Alternatively, strains of R. gnavus (or closely related species) will be screened
for those that do not produce the anti-inflammatory molecule, and their genomes will be compared to identify
genes associated with anti-inflammatory activity.
The anti-inflammatory activity of the molecule is abolished when Myd88 is knocked out; therefore, it is likely
recognized by the immune system through a TLR. Each TLR will be knocked out to determine how the anti-
inflammatory molecule is recognized by the immune system. The response of the immune system will also be
characterized by RNA-seq. The clinical relevance of the anti-inflammatory molecule will be established by
searching for its presence in previously collected metabolomic data from patient stool samples. Alternatively,
presence and expression of the biosynthetic genes will be determined by mining previously collected
metagenomic and transcriptomic data from these same patient samples. Finally, a mouse IBD model will be
used to determine the effects of R. gnavus and its purified immunomodulator on disease initiation, severity, and
progression. This work will expand our knowledge of how a member of the gut microbiome modulates the
immune system and its relevance for IBD, and may also identify potential avenues for therapeutic intervention.

## Key facts

- **NIH application ID:** 9859409
- **Project number:** 5F32GM126650-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Matthew Thomas Henke
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2018-03-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859409

## Citation

> US National Institutes of Health, RePORTER application 9859409, Elucidating the role of an immunomodulator from a gut microbe in inflammatory bowel disease (5F32GM126650-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9859409. Licensed CC0.

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