# Quantification of bacterial strain count in the human gut microbiome in health and disease

> **NIH NIH F30** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $47,374

## Abstract

PROJECT SUMMARY
In Inflammatory Bowel Disease (IBD), the gut microbiome demonstrates reduced species diversity that can
then be reversed following FMT. However, no study has identified a common pattern of microbiome alteration
that is causally related to IBD nor has any study elucidated the mechanisms underlying FMT success in the
subset of individuals with IBD that respond. In FMT, both species and strain diversity are increasing but
currently studies only track changes in species diversity, resulting in a fundamental feature of the microbiome
that is changing but not measured in trials or in cross sectional studies of comparing with healthy and IBD
microbiomes. Thus, it is unclear whether it is the increase in species or strain diversity that is critical to FMT
success or if there are unique differences in the strain-level structure of the IBD microbiome. Since microbial
functional variation is found at the strain level, a functional understanding of microbiome composition in IBD
may lie at the strain level. However, no studies so far have systematically characterized the strain-level
microbiome structure in health or disease. This proposal aims to define strain count—the number of unique
strains each bacterial species stably maintains in an individual—in healthy and IBD microbiomes and to further
investigate the functional impact of strain count in disease. We will quantify strain count by employing a high-
throughput culturing technique to isolate and sequence thousands of gut bacterial isolates for all culturable
species in a breadth-focused manner and validate our breadth-focused quantifications by using a depth-
focused approach to intensely sequence more genomes from ten of the most common gut species. For our
depth-sequencing, we will use gnotobiotic mice fed different diets to enrich for low abundance strains. This
experimental approach allows us to increase the efficiency by which we capture the strains of a particular
species and achieve a more accurate quantification of strain count. Aim 1—Based on our preliminary findings,
we anticipate that there is a limited number of strains each species can maintain in the gut microbiota and that
our method sequences a sufficient number of genomes to quantify strain count. We aim to define strain
count in healthy and IBD microbiomes which will allow for higher resolution, functional investigations
into microbiome composition in disease. In Aim 2—we will investigate the effect of increasing strain
count on colitis severity. We will combine defined communities of strains isolated from an IBD and healthy
microbiota in a gnotobiotic T cell transfer colitis model. The defined communities will allow us to specifically
increase strain count while holding species diversity stable. By studying the functional role of strain count, we
can uncover the potential contributions of microbiome strain-level architecture to the disease process and
identify appropriate targets for optimizing FMT for the treatment o...

## Key facts

- **NIH application ID:** 10753546
- **Project number:** 5F30DK131862-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Alice Yulan Chen-Liaw
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $47,374
- **Award type:** 5
- **Project period:** 2021-12-23 → 2025-12-22

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10753546

## Citation

> US National Institutes of Health, RePORTER application 10753546, Quantification of bacterial strain count in the human gut microbiome in health and disease (5F30DK131862-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10753546. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
