# The Influence Of Gut Microbiota Stability In Inflammatory Bowel Disease

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $50,197

## Abstract

PROJECT SUMMARY
Inflammatory Bowel Diseases (IBD), consisting of Ulcerative colitis (UC) and Crohn's disease (CD),
are chronic progressive inflammatory conditions of the intestine. Numerous lines of evidence suggest
their origins lie in an overaggressive response of the host immune system towards the gut microbiota
in a genetically susceptible host. We hypothesize a key feature of IBD is the persistent colonization
by colitogenic microbial strains in the absence of sufficient colitoprotective strains that over years to
decades can drive the progressive inflammation and damage associated with IBD. To test this
hypothesis we propose three Aims. In Aim 1, we will sample, every year for five years, the fecal
microbiota of individuals with Inflammatory Bowel Disease (UC or CD) and healthy controls. To
understand the implications of gut microbiota stability in the context of a gut microbiota manipulation
intervention, we will also longitudinally sample recipients of fecal microbiota transplantation (FMT) for
ulcerative colitis, after FMT therapy has ended, for up to 5 years. We will use metagenomics
combined with high throughput microbial isolation and genome sequencing to identify the stable and
transient microbes in each individual's microbiota and determine if individuals with IBD have
significantly altered gut microbiota stability. We will also track the loss of engrafted FMT donor strains
in subjects in remission post-FMT overtime to associate strain loss with long-term-relapse. In Aim 2,
we will use gnotobiotic T-cell transfer colitis mice colonized with subsets of each microbiota to identify
colitogenic and colitoprotective microbial strains and to determine if colitogenic or colitoprotective
organisms are preferentially found in the stably colonized community members. We will also
determine if colitogenic and colitoprotective strains drive unique baseline immune tones when
colonized in unchallenged gnotobiotic mice. With an aim towards future human translation, we will
search for minimal colitoprotective subsets from previously identified colitoprotective communities,
and we will determine if strains lost post-FMT are colitoprotective, in UC subjects that achieve
remission but subsequently relapse. Together these aims will help us determine if individuals with
Inflammatory Bowel Disease are enriched in stably colonized colitogenic organisms whose
elimination might form a novel therapeutic intervention for the treatment or prevention of Inflammatory
Bowel Disease and if healthy individuals are enriched in stably colonized colitoprotective organisms
that might form the basis of a novel IBD therapeutic.

## Key facts

- **NIH application ID:** 11057369
- **Project number:** 3R01DK112978-06S1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Jeremiah James Faith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $50,197
- **Award type:** 3
- **Project period:** 2019-03-04 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11057369

## Citation

> US National Institutes of Health, RePORTER application 11057369, The Influence Of Gut Microbiota Stability In Inflammatory Bowel Disease (3R01DK112978-06S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11057369. Licensed CC0.

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