# Caenorhabditis Elegans: a Model for Genetic Interaction between the Gut Microbiota and Intestinal Epithelial Cells

> **NIH NIH F32** · COLORADO STATE UNIVERSITY · 2022 · $69,677

## Abstract

Project Summary
Inflammatory and infectious diseases are among the leading causes of death worldwide. Coordination and
regulation of immune defenses are essential to combating infection and preventing aberrant inflammatory
responses. This is especially important within the gastrointestinal tract where potential pathogens must be
differentiated from commensal microbes. Deleterious alterations in our gut microbial community (dysbiosis) are
associated with numerous diseases. At the forefront of host-microbe interactions are intestinal cells which act as
a critical barrier and interface with our luminal environment. Intestinal cells possess a repertoire of innate immune
receptors and defense mechanisms, allowing them to directly respond to and modulate gut bacteria. Thus, they
are thought to play a critical role in establishing and maintaining the beneficial symbiotic relationships we develop
with our gut microbiota. Remarkably, several fundamental processes underlying these host-microbe interactions
remain poorly understood, including how intestinal cells differentiate between commensals and pathogens or
which intestinal cell responses promote commensal selection in the gut. The long-term objective of this proposal
is to determine how intestinal cells directly contribute to the selection and maintenance of commensal gut
bacteria. The proposed research approaches this objective by leveraging the tractability and simplicity of the
model organism C. elegans to provide the fine-scale spatial resolution needed to dissect the intricacies
underlying host-microbe interactions. C. elegans is a model of intestinal development and innate immunity that
also harbors a diverse gut microbiome in natura, making C. elegans an excellent system for studying microbial-
induced innate immune responses. Aim 1 will determine how bacteria- and community-specific immune
responses are organized in the intestine by evaluating the transcriptional response of intestinal cells to
commensal and pathogenic gut bacteria using single-cell RNA-sequencing (scRNA-seq). This will reveal unique
innate immune signatures among intestinal cells throughout the gut based on bacterial exposure. Preliminary
evidence from our embryo scRNA-seq dataset highlight several spatially distinct immune genes including the C-
type lectins (CLECs), which have a well-defined role in bacterial recognition in mammals. Aim 2 will determine
how intestinal cells regulate commensal colonization in the gut by testing the role of innate immune receptors,
specifically CLECs, in selecting for and maintaining commensal bacteria. Using a combination of molecular
biology and microscopy techniques, aim 2 will elucidate the cohorts of CLECs required to recognize and respond
to commensal gut bacteria. Results from this proposed investigation will clarify how innate immunity is regulated
on a transcriptional level throughout the intestine and how it contributes to the selection and maintenance of
host-microbe relationships ...

## Key facts

- **NIH application ID:** 10537455
- **Project number:** 1F32DK131636-01A1
- **Recipient organization:** COLORADO STATE UNIVERSITY
- **Principal Investigator:** Jessica L Hill
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $69,677
- **Award type:** 1
- **Project period:** 2022-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537455

## Citation

> US National Institutes of Health, RePORTER application 10537455, Caenorhabditis Elegans: a Model for Genetic Interaction between the Gut Microbiota and Intestinal Epithelial Cells (1F32DK131636-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10537455. Licensed CC0.

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