# Immunomodulation by Commensal Microbiota: Role in Ischemic Brain Injury

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $370,781

## Abstract

Project Summary/Abstract
Stroke is a prevalent and devastating disease with limited therapeutic options. Inflammation and
immune cells are major components in the pathophysiology of ischemic stroke and contribute to acute
and delayed tissue injury. However, our incomplete understanding of the factors regulating the immune
responses triggered by cerebral ischemia remains a significant obstacle to the development of effective
therapeutic interventions based on modulating post-ischemic inflammation. Besides activation of brain
resident immune cells, ischemic stroke is characterized by the recruitment of peripheral innate and
adaptive immune cells that participate in the inflammatory response and contribute to the damage.
Commensal microbiota that populate epithelial surfaces play a defining role in shaping the immune
system, the development, maintenance and function of which depends critically on the relative
abundance and composition of the different microbial species. In particular, intestinal commensal
bacteria, the most abundant symbiotic compartment in the body, have emerged as a potent regulator of
the immune system. Remarkably, the gut microbiota influence the development and proliferation of
immune cells (γδT cells and Treg), which have been strongly implicated in ischemic brain injury. These
observations raise the possibility that the microbiota have the potential of modulating the outcome of
cerebral ischemia. The long-term goal of this research program is to elucidate the role of intestinal
microbiota in stroke pathobiology and develop the experimental framework for new preventative and
therapeutic approaches for ischemic stroke. In the present application, we will test the hypothesis that
commensal intestinal microbiota are a critical determinant of stroke outcome by modulating the immune
system and inflammatory response to cerebral ischemia. This hypothesis, supported by relevant
preliminary results, will be tested by determining: (a) the impact of antibiotic-induced modification of the
gut flora (intestinal dysbiosis) on stroke outcome (Aim 1), (b) the changes in the peripheral and brain
immune system evoked by such dysbiosis and their role in ischemic brain injury (Aim 2), and (c) the
cellular and molecular events leading to this immunomodulation (Aim 3). These goals will be achieved
using a mouse model of transient focal cerebral ischemia with assessment of histological and
neurological outcome together with a novel model of microbial dysbiosis. This proposal may open the
way to new avenues for stroke prevention and therapy based on modulation of the immune system by
the gut microbiota, using approaches already in the clinical arena.

## Key facts

- **NIH application ID:** 9963402
- **Project number:** 5R01NS094507-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Josef Anrather
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,781
- **Award type:** 5
- **Project period:** 2016-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963402

## Citation

> US National Institutes of Health, RePORTER application 9963402, Immunomodulation by Commensal Microbiota: Role in Ischemic Brain Injury (5R01NS094507-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9963402. Licensed CC0.

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