# Identifying immunoregulatory gut bacteria in type 1 diabetes and autoimmunity

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $381,062

## Abstract

Abstract
It is known that patients with type 1 autoimmune diabetes (T1D) have altered gut microbiota, and potentially
pathogenic bacteria, which are increased, have been much studied. However, less is known of the impact
on the host immune system, and in particular on immune regulation, of the bacterial species, which are
significantly reduced. We hypothesized that the reduced bacterial species are associated with the lack of
immune tolerance in T1D, especially the bacterial species that are commonly present in both the gut and
oral cavity. Taking advantage of availability of germ free animals and a pure V dispar strain from human
oral cavity, we tested this hypothesis by using V. dispar to colonize germ-free (GF) mice and assessed the
effect of V. dispar on immune cells. It is intriguing that we found that V. dispar promoted Treg cells in most
of the peripheral lymphoid tissues examined and the majority of the Treg cells expressed neuropilin-1 and a
higher frequency of the Tregs were IL-10 producers. These in vivo effects of V. dispar could also be
mirrored in vitro with direct contact of immune cells to V. dispar. V. dispar induced Tregs are ready to
suppress naturally primed diabetogenic T cells in vitro. More importantly, V. dispar ameliorated the severity
of insulitis in NOD mice. Further, V. dispar produce high level of short chain fatty acids (SCFAs) acetate
and propionate. In addition, V. dispar markedly improved gut permeability. Moreover, the induction of
Tregs and IL-10 producers, as well as improvement of gut permeability by V. dispar were found when tested
in both GF-NOD and GF-B6 mouse strains, suggesting that V. dispar has a general immune regulatory
effect.. Our preliminary data are compelling, and lead us to hypothesize that V. dispar are important in
maintaining immune regulation, and hence immune tolerance. We propose the 3 specific aims to test our
hypothesis using GF NOD and GF B6 mice, as well as the mouse strains in which dendritic cells or Tregs or
short chain fatty acid (SCFA) receptor are specifically targeted (commercially available). Our approach
using V. dispar as a model system will also signpost the study of other bacteria species that were markedly
reduced in the gut of patients with T1D. If our hypothesis is proved to be correct, our study will help with the
design of future novel therapy for T1D and other autoimmune disorders, for which, we will “return“ to human
studies.

## Key facts

- **NIH application ID:** 10811684
- **Project number:** 5R01DK130318-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Li Wen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $381,062
- **Award type:** 5
- **Project period:** 2022-05-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811684

## Citation

> US National Institutes of Health, RePORTER application 10811684, Identifying immunoregulatory gut bacteria in type 1 diabetes and autoimmunity (5R01DK130318-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10811684. Licensed CC0.

---

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