# Microbial Regulation of Microglial Function

> **NIH NIH K08** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $195,480

## Abstract

Project Summary/Abstract
This proposal is for a four-year research career development program, focused on the study of the microbiome’s
contribution to the regulation of microglial maturation and function including experience-dependent synaptic
pruning. The candidate has already been appointed an Instructor in the Department of Medicine at Weill Cornell
Medical Center. The proposal is a natural extension of the candidate’s previous research into microglial-neuronal
interaction, synaptic plasticity, and behavioral outcomes in mice. It outlines a plan for the candidate to achieve
his goal of becoming an expert in the microbial regulation of critical central nervous system processes, extending
the training of the candidate in two dimensions, which are reflected in the mentorship of Drs. Conor Liston and
David Artis: 1. Identification of microbially-derived signals that alter the maturation and function of microglia, and
2. Alterations in microglial function that regulate experience-dependent synaptic refinement. The proposed
experiments and multi-faceted training plan will impart the candidate with a unique combination of skills that will
position him to transition into a successful independent career as a physician-scientist studying the contribution
of peripheral organ system dysfunction to alterations in cognitive function and affective states.
Alterations in the microbiota have been associated with multiple neuropsychiatric disorders in small-scale human
correlational studies, and animal studies utilizing germ-free (GF) mice lacking a microbiota from birth, or animals
rendered acutely dysbiotic by antibiotic treatment have demonstrated defects in the normal physiology of multiple
CNS regions and cell populations including synapse-level changes in the context of experience. Amongst
affected cell populations, the CNS tissue-resident macrophage known as microglia have been shown by us and
others to be heavily altered in the absence of a normal microbiota. Given the known importance of microglia in
regulating the formation, stability, and plasticity of synapses within both the developing and adult mouse brain,
they likely represent an important conduit through which microbiota-derived signals regulate normal experience-
dependent synaptic plasticity and ultimately animal behavior. The goal of my proposal is to investigate the role
of the microbiota in modulating microglial function in the adult brain. Specifically, this proposal investigates how
changes to the microbiome alter microglial-neuronal interaction by: 1. Identifying the microbially-derived small
molecule signals by which the microbiome alter mouse and human microglial maturation and function in vitro; 2.
Testing the role of these metabolites in regulating microglial-dependent synaptic refinement in a model of
experience-dependent plasticity. Collectively, these experiments provide novel insight into the role of the
microbiome and its metabolites in regulating microglial function including...

## Key facts

- **NIH application ID:** 10894682
- **Project number:** 5K08MH130773-03
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Christopher Neal Parkhurst
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $195,480
- **Award type:** 5
- **Project period:** 2022-08-05 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894682

## Citation

> US National Institutes of Health, RePORTER application 10894682, Microbial Regulation of Microglial Function (5K08MH130773-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894682. Licensed CC0.

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