# Detrimental Effects of Age Related Dysbiosis

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · 2022 · $593,950

## Abstract

PROJECT SUMMARY
In recent years, it has become apparent that a “microbiota-gut-brain” axis exists where bidirectional
communications occur between the gut, its microbiota contents, and the brain. In this proposal, we will develop
the hypothesis that this “microbiota-gut-brain” axis is operational after stroke. That is, stroke produces gut
dysbiosis, a pathological change in the gut microbiota, and gut dysbiosis, as occurs with aging, negatively affects
outcomes following stroke. Our overall hypothesis is that age-related dysbiosis contributes to the high
mortality and poor functional recovery seen after stroke in aged animals. Reversing dysbiosis in aged
mice by manipulating the resident bacterial population (“the microbiota”) will lead to enhanced recovery
after experimental stroke. We support our hypothesis with strong preliminary data. a) Gut dysbiosis occurred
with aging in mice. (b) Changes in the innate and adaptive immunity, occurring with age, were reversed with
transfer of young microbiota into aged mice. (c) Gavaging the gut microbiota from young mice (3 months) into
aged mice (18-20 months) after experimental stroke improved recovery. (d) A deficit of short chain fatty acids
(SCFAs), primarily acetate, propionate, and butyrate, in the gut of aged mice is associated with poor outcome
after stroke. (e) Post-stroke gavage of short chain fatty acid producing bacteria (probiotics) enhanced
recovery in aged mice. We will develop the idea that age-related changes in T-cell subsets in both the gut
and the brain mediate these detrimental effects and that deficiency of SCFAs is responsible for these
detrimental T-cell changes. The main goal of this proposal is to understand how the components of the
“microbiota-gut-brain” axis change with age and stroke with a focus on brain inflammation (microglia and brain
resident T-cells; Aim 1), gut inflammation (regulatory and gamma delta T-cells; Aim 2) and bacterial products
(the short chain fatty acids, butyrate, acetate, and propionate) to enhance the recovery from stroke in aging mice
(Aim 3). We will manipulate the biome in entirety (heterochronic fecal transfers), with bacterial metabolites (short
chain fatty acids), and with targeted next-generation probiotics. Furthermore, we will determine the role of each
short chain fatty acid on stroke recovery by directly infusing into the cecum and colon through a chronically
indwelling cannula. Stroke is now the most common cause of long-term disability in the US and the incidence
continues to rise with our aging population. The “microbiota-gut-brain axis” after stroke is a critical and novel
area of investigation to fully understand the pathophysiology of stroke and offers a promising approach to
therapeutic interventions to improve recovery from stroke, especially in the elderly.

## Key facts

- **NIH application ID:** 10394286
- **Project number:** 5R01NS103592-05
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
- **Principal Investigator:** ROBERT M BRYAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $593,950
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394286

## Citation

> US National Institutes of Health, RePORTER application 10394286, Detrimental Effects of Age Related Dysbiosis (5R01NS103592-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10394286. Licensed CC0.

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