# Molecular mechanisms underlying microbial modulation of host behavior

> **NIH NIH R35** · UNIVERSITY OF FLORIDA · 2023 · $372,143

## Abstract

A central question in behavioral biology is how environmental and genetic factors shape behavioral traits,
allowing for substantial individuality. Homeostatic behaviors like feeding and food preferences are prime
examples of genetic predispositions interacting with the food environment to produce diverse feeding habits.
However, these programs are further modified by host-associated microbes, suggesting the overall systems
controlling behavioral phenotype is far more complex than first anticipated. The critical questions that remain
to be addressed are: to what extent do host-microbe interactions contribute to individual differences in behavior?
Specifically, how does gene regulation of behavior operate in the context of host-microbe symbiosis? Implicit in
this question is the hypothesis that perturbation of host-microbe symbiosis results in aberrant behavioral
outcomes in certain individuals or populations, a topic fundamental to human health yet unsolved.
 The goal of my research program is to define how behaviors are shaped by host-microbe interactions.
My lab studies foraging and food choice behaviors in the fly Drosophila melanogaster, using a gnotobiotic system
I developed that permits precise configuration of the fly microbiome. I hypothesize that feeding behavior and
food preferences are the product of host genetics-microbiome interactions, which determine, in part, an
individual’s long-term health. Our recent data show that foraging and diet selection preferences vary by the
microbiome, and altering the microbiome triggers transcriptional changes in specific cell clusters within the fly
brain, involving genes predicted to affect behavior. In this five-year plan, I will leverage fly genetics and state-
of-the-art genomics and metabolomics tools to identify the gene regulatory networks and mechanisms
underlying microbial modulation of host behavior. Expected outcomes include comprehensive gut endocrine
signaling and inter-organ communication maps at single-cell transcriptome scale and metabolite-gene
interactions networks. The causal effects of microbiome-responsive genes, neuropeptides, and metabolites on
host feeding behavior and food preferences will be revealed. Since we know little about how the interplay of
host genetics and microbiome contribute to complex behavior, my research has the potential to advance
fundamental knowledge in behavioral genetics but also to identify genes or processes that may function
similarly in Drosophila and mammals as targets to treat behavioral disorders, such as eating disorders and obesity.

## Key facts

- **NIH application ID:** 10701899
- **Project number:** 5R35GM147651-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Chun Nin Adam Wong
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $372,143
- **Award type:** 5
- **Project period:** 2022-09-09 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10701899

## Citation

> US National Institutes of Health, RePORTER application 10701899, Molecular mechanisms underlying microbial modulation of host behavior (5R35GM147651-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10701899. Licensed CC0.

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