# The role of sulfidogenic microbes in quiescent Crohn’s disease with persistent symptoms

> **NIH NIH R03** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $117,000

## Abstract

Even in the absence of active inflammation, persistent symptoms are reported in up to 46% of patients with
Crohn's disease (CD). Persistent symptoms in quiescent CD (labeled qCD+S in this grant) result in significant
deterioration in quality of life, increase risk for future opioid use, and are among the top drivers of healthcare
costs in CD. Increased intestinal permeability and visceral hypersensitivity are key pathogenic features in
patients with qCD+S. Although initially believed to be related to sub-clinical inflammation, recent studies have
shown no difference in the rate of persistent symptoms in CD patients with and without deep histologic
remission. Importantly, evidence-based treatments do not exist due to lack of understanding of the
mechanisms leading to qCD+S. Recently, altered gut microbiota have been implicated but the mechanisms by
which altered microbial communities may mediate qCD+S remain unknown. A promising development shown
by our preliminary data is enrichment of sulfidogenic bacteria and sulfur metabolic pathways in patients with
qCD+S. Dietary sulfur is metabolized by the intestinal microbiota to produce hydrogen sulfide (H2S), which is
rapidly detoxified by host mitochondrial enzymes to protect the host against toxic effects of H2S. However, at
higher concentrations, microbial-derived H2S may overwhelm host mitochondrial H2S detoxifying capacity. As a
result, increased H2S levels may result in mitochondrial dysfunction, disrupt intestinal barrier function, and
exert pro-nociceptive effects. Diet, particularly consumption of animal protein, is the major determinant of H2S
production in the gut. However, the relationship between diet, sulfidogenic microbes, epithelial barrier function,
and visceral sensation in qCD+S is unknown. Thus, there is a critical need to examine the interplay between
diet, sulfidogenic microbes, host responses, and persistent symptoms in quiescent CD. The long-term goal of
this project is to accelerate development of microbial-based treatments for qCD+S. The central hypothesis is
that enrichment of sulfidogenic microbes result in dysregulated host responses, including intestinal barrier
dysfunction and visceral hypersensitivity, which may be amenable to dietary intervention. In Aim 1, we will
determine how sulfidogenic microbes influence host gene expression in qCD+S by integrating existing multi-
omic datasets from a multi-center cohort, including metagenomic and untargeted metabolomics data from stool
samples as well as host gene expression from intestinal biopsies. In Aim 2, we will perform a pilot study to
determine the feasibility and tolerability of a low sulfur diet in qCD+S. We will also test whether a low sulfur diet
may improve intestinal permeability, visceral sensation, and persistent symptoms and whether these changes
are mediated by perturbations in sulfidogenic microbes. Completion of these aims will provide fundamental
insights into diet-host-sulfidogenic microbial interactions in q...

## Key facts

- **NIH application ID:** 10866086
- **Project number:** 1R03DK139095-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Allen A Lee
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $117,000
- **Award type:** 1
- **Project period:** 2024-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866086

## Citation

> US National Institutes of Health, RePORTER application 10866086, The role of sulfidogenic microbes in quiescent Crohn’s disease with persistent symptoms (1R03DK139095-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10866086. Licensed CC0.

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