# The Study of Families with Heritable Crohn's Disease to Support Rational Design of Microbiota-based Therapies

> **NIH NIH K23** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $197,412

## Abstract

Project Summary/Abstract
The cause of Crohn's disease (CD) is believed to be rooted in the interactions between genetic susceptibilities
and exposures to environmental factors, such as specific gut microbes. Unfortunately, the complexity of these
interactions makes it difficult to understand what portion of CD risk is modifiable, and particularly whether gut
microbiome compositions can be altered to overcome one's underlying and fixed genetic predisposition. This
proposal will address whether individuals at high genetic risk for CD, but who never develop disease, harbor
characteristic gut microbial signatures that signal protection from CD. It will furthermore address whether
protective microbiomes can be transferred to diminish, delay, or prevent CD activity in others. Aim 1 will entail
the study of multigenerational families with multiplex CD – with the rationale that families, sharing common
living environments, meals, and behaviors, will minimize common confounders of human microbiome studies.
Individuals will be stratified by a polygenic risk score to better identify those at highest genetic risk but remain
disease-free and who are hypothesized as being most likely to harbor intestinal microbiomic and metabolomic
signatures that characterize disease protection. In Aim 2, select fecal biospecimens (collected in Aim 1)
containing putative protective microbiomes will be transplanted into a germ-free CD mouse model. These mice
will then be characterized by their phenotypic, microbial, metabolomic, and immune responses and assessed
for alterations in disease onset and severity. These studies will provide insights into microbially-mediated
modulators of CD activity; for example, clarifying the yet unknown reason why fecal transplants are very
effective for only a small portion of inflammatory bowel disease cases and why outcomes appear to be heavily
donor-dependent.
Coupling the study of an enriched human population with an animal model, to mechanistically test candidate
protective microbiomes, will streamline the scientific approach and expedite the transition of promising study
findings into clinical care. The scientific proposal and associated training plan will furthermore prepare the PI,
so that she will be well-equipped to lead future studies of host-microbe dynamics in inflammatory bowel
disease as an independent translational investigator.

## Key facts

- **NIH application ID:** 9892576
- **Project number:** 1K23DK119544-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** LEA A CHEN
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $197,412
- **Award type:** 1
- **Project period:** 2020-01-16 → 2020-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892576

## Citation

> US National Institutes of Health, RePORTER application 9892576, The Study of Families with Heritable Crohn's Disease to Support Rational Design of Microbiota-based Therapies (1K23DK119544-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9892576. Licensed CC0.

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