# Impact of dysbiosis on the development of age-related inflammation

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $70,596

## Abstract

Project summary
The resident gut microbiota and the host immune system have co-evolved for millennia. However, modern
societal conditions have disturbed this co-evolution, coinciding with a steep rise in immune-mediated diseases.
Bacterial translocation across the intestinal barrier and into extraintestinal organs such as the visceral adipose
tissues can have major pathological consequences. We recently discovered that aging is associated with
formation of tertiary lymphoid structures, known as Fat-associated lymphoid clusters (FALCs), in the visceral
adipose tissue. As an individual ages, the abundance of anti-inflammatory gut bacteria decreases with a parallel
increase in opportunistic pathogens, ultimately leading to disruption of intestinal immunity and barrier function.
In two recent studies, the gut commensal species Enterococcus gallinarum was found to have high translocation
efficacy, with the ability to translocate to the liver and induce autoimmunity in genetically predisposed mice. In
our preliminary experiments, we found that two different strains of E. gallinarum exhibit distinct capacities for
translocation, and that rates of translocation for a single E. gallinarum strain vary dramatically between mice
mono-colonized with E. gallinarum versus mice colonized with E. gallinarum in the presence of a complex gut
microbial community. We hypothesize that translocation of gut microbes to visceral adipose tissue results in
FALC formation and age-related inflammation leading to metabolic dysfunction. In this application, we propose
to: 1) determine the effect of E. gallinarum translocation and persistence on aging-associated FALC formation
and inflammation, and 2) elucidate the mechanism(s) that enable E. gallinarum to translocate and induce aging-
associated FALC formation and inflammation. These studies will provide insight into the fundamental
mechanisms by which commensal bacteria translocate across the intestinal barrier and induce age-related
inflammation. Thus, they may illuminate potential targets for novel therapeutic strategies delay chronic aging
with age.

## Key facts

- **NIH application ID:** 10331167
- **Project number:** 3R01AG068863-02S1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** VISHWA DEEP DIXIT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,596
- **Award type:** 3
- **Project period:** 2020-09-30 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10331167

## Citation

> US National Institutes of Health, RePORTER application 10331167, Impact of dysbiosis on the development of age-related inflammation (3R01AG068863-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10331167. Licensed CC0.

---

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