# The Young Gut Microbiome: A Fountain of Youth for Brain Injury in the Aged?

> **NIH NIH RF1** · NORTHWESTERN UNIVERSITY · 2024 · $249,654

## Abstract

PROJECT SUMMARY
Patients aged 65 and older account for an increasing portion of traumatic brain injury (TBI)
patients. TBI contributes to over one third of trauma related deaths and aged TBI patients suffer
increased morbidity and mortality compared to young TBI patients. The impact of TBI is also
highlighted through its significant long-term cognitive and psychiatric complications suffered by
survivors. After TBI, microglia adopt a constitutively active state leading to an increased
inflammatory response. Our previous studies show that TBI results in an influx of monocytes,
monocyte derived leukocytes, and CD8+ T-cells into the brain. Additionally, we demonstrated that
infiltrating inflammatory immune cells mediate injury and neurocognitive outcomes after TBI, and
reduced infiltration attenuates poor neurologic outcomes and improves behavioral outcomes. But
the interplay between microglia, immune cells, and the gut is still poorly understood. To assess
recruitment of monocytes and T-cells by activated microglia, we will deplete microglia in young
and aged mice and observe immune cell infiltration after TBI. Microglial depletion will occur
through a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622 formulated into rodent
chow. After microglia depletion, mice will undergo TBI or sham injury. Activation, proliferation, and
differentiation of monocyte and T-cell subtypes will be assessed through flow cytometry to
determine whether microglial depletion attenuates immune cell accumulation. To investigate the
impact of the gut microbial community on immune infiltration and microglial activation we will
utilize a murine FMT model. We will prepare fecal slurry from young and aged mice to administer
to aged mice either before or after TBI with PBS as a vehicle control. Mice will undergo
neurocognitive testing to assess phenotypic alterations due to FMT. We will assess
neuroinflammation in these mice by flow cytometry, microglial gene expression through
scRNAseq, and clonal expansion of T-cells through scTCRseq. Overall, this project will assess
the interplay of microglia, infiltrating immune cells, and the gut in the aged brain after TBI,
potentially determining routes for therapeutic development. This project will expand my
capabilities through advanced training in neuroimmunology, RNA sequencing, and neurocognitive
testing while utilizing my expertise in immunology and advanced flow cytometry. I will present my
findings in numerous professional settings for peer review including national conferences and I
will publish my findings in peer-reviewed journals in preparation for a future MOSAIC K99/R00
award.

## Key facts

- **NIH application ID:** 11031784
- **Project number:** 3RF1NS135652-01S1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** STEVEN J SCHWULST
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $249,654
- **Award type:** 3
- **Project period:** 2024-04-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11031784

## Citation

> US National Institutes of Health, RePORTER application 11031784, The Young Gut Microbiome: A Fountain of Youth for Brain Injury in the Aged? (3RF1NS135652-01S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11031784. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*