# Impact of symbiotic protists on intestinal T cell homeostasis and inflammation.

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $492,192

## Abstract

Project Summary
The gut microbiome exerts a tremendous influence on the function of the immune system at
homeostasis and during inflammatory insults. Most research has focused on how individual
bacteria or particular bacterial configurations interact with the immune system, but the
microbiota contains other forms of microbial life, including protists. Several species of
common and non-pathogenic protists in mice, from the genus Tritrichomonas, induce a type
2 immune response in the small intestine without causing overt pathology. In addition, other
species of Tritrichomonads were later discovered that promote Th1 and Th17 cells in the
colon. However, it is unclear if these differences in mucosal immunity are related to species-
specific effects or other factors. The phylogenetic relationship between intestinal
Tritrichmonas species is poorly understood as their genomes remain unsequenced.
Furthermore, the immune landscape and microbiota composition varies greatly between the
small intestine and colon, which further complicates comparisons between these
Tritrichomonas species and their immune effects. To overcome these obstacles, we isolated
two species of Tritrichomonads that elicit either a Th1 or Th2 immune response in the small
intestine. In Aim 1, we will generate high-quality genomes for each protist and measure their
output of key immunomodulatory metabolites. In Aim 2, we will characterize the effects of
these two protists on the adaptive immune system. We will determine immune mechanisms
that respond to each species of Tritrichomonas. Finally, in Aim 3, we will determine how
these two Tritrichomonads impact Crohn’s Disease in a mouse model. These studies will
establish key genomic tools and insights into Tritrichomonas species and mechanisms that
influence on intestinal immunity. Furthermore, this project will evaluate the possible benefits
of these symbiotic protists on Crohns’s disease, leading to novel therapeutic approaches to
treat IBD.

## Key facts

- **NIH application ID:** 10570264
- **Project number:** 5R01DK128292-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Michael R Howitt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $492,192
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10570264

## Citation

> US National Institutes of Health, RePORTER application 10570264, Impact of symbiotic protists on intestinal T cell homeostasis and inflammation. (5R01DK128292-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10570264. Licensed CC0.

---

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