# Molecular determinants of host-feeding manipulation and microbial colonization

> **NIH NIH DP2** · YALE UNIVERSITY · 2023 · $1,338,750

## Abstract

Project Summary
 All animals live in environments surrounded by microbes, yet the impact of bacteria on nervous
systems has been relatively under-studied. Recent data suggests that commensal gut bacteria may be capable
of modulating host behavior. Gut bacteria benefit from nutrients consumed by their host and because these
bacteria must be transmitted largely via diet, manipulation of host feeding behavior is a principal mode by
which resident microbes can influence the gut microbial community. Due to the dynamic nature of such an
interaction, studying feeding manipulation has been either challenging or impossible to date in most systems.
First, we must identify systems in which both host and microbe are amenable to genetic manipulation, and
which enable high-throughput behavioral screening in response to defined and naturalistic conditions. Here, we
propose to comprehensively study this phenomenon for the first time in any experimental system, using the
roundworm C. elegans — in combination with its natural associated bacteria — to gain mechanistic insights
into inter-organismal signals driving host-microbe interactions and decision making. C. elegans is a bacterial-
feeding nematode that is often found in rotting plant material and is commonly colonized by microbes. C.
elegans has some of the most extensive molecular, neurobiological and genetic tools of any multicellular
eukaryote, and, coupled with the ease of gnotobiotic culture in these worms, represents a highly attractive
system in which to study microbial influence on host behavior.
 I have recently shown that in C. elegans, gut bacteria can influence chemosensory decisions — a proxy
for feeding behavior in certain contexts — resulting in increased preference for odors produced by these
enteric microbes. In parallel preliminary work, I have found that olfactory plasticity upon gut colonization by
diverse microbes correlates with gut colonization patterns in naturalistic settings. Together, these findings
suggest that the C. elegans native gut microbiota may be capable of impacting microbiome assembly by
influencing feeding behavior. In this proposal, we aim to establish C. elegans as a system to study feeding
manipulation by developing tools to identify the behavioral parameters which influence microbiome structure in
naturalistic settings. We propose to experimentally isolate ingestion from locomotory behavior through the
development of novel microfluidics imaging devices. We will develop new behavioral assays in 2- and 3-
dimensional arenas to present microbial communities mimicking the worms’ natural environment. We will then
identify the molecular basis of microbial-dependent changes in olfactory behaviors using naturalistic microbial
communities. Together, we propose to develop a new field of feeding manipulation by gut microbes, with C.
elegans centered as a preeminent model. We anticipate that the principles we identify in this proposal should
generalize to multiple systems and th...

## Key facts

- **NIH application ID:** 10686470
- **Project number:** 1DP2GM154014-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Michael Patrick ODonnell
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $1,338,750
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10686470

## Citation

> US National Institutes of Health, RePORTER application 10686470, Molecular determinants of host-feeding manipulation and microbial colonization (1DP2GM154014-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10686470. Licensed CC0.

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