# ROLE OF STRESS IN GUT IMMUNE INTERACTIONS WITH COMMENSAL BACTERIA

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $701,408

## Abstract

Stress is a trigger for flares of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). Patients
with IBD, and at least a subset of patients with IBS, also have alterations in the gut microbiota (aka dysbiosis)
and alterations in the gut immune responses. While studies have demonstrated that immune responses can
have effects on GI motility and symptoms, a major gap in our understanding of stress as a trigger for IBD
and IBS flares is how, and if, stress is causal in dysbiosis and in alterations in gut immune responses
and if these changes contribute to symptoms.
We discovered that patients with diarrhea predominant IBS (IBSd) had dysbiosis on 16S rDNA sequencing of
feces and increased binding of secretory IgA to fecal bacteria, indicating that IBSd patients had increased
antigen specific immune responses to their gut bacteria. Using a mouse model, we found that stress likewise
induced diarrhea, visceral hypersensitivity, dysbiosis and increased IgA binding to gut bacteria, recapitulating
our findings in human IBSd patients. Notably the GI symptoms following stress were dependent upon the
microbiota as germ free mice did not develop diarrhea following stress. Further, fecal microbiota
transplantation (FMT) of microbiota from stressed, but not control, mice recapitulated the immunologic features
of stress. Moreover, we observed that stress-induced dysbiosis allows the translocation of commensal
bacteria to the mesenteric lymph node (MLN) facilitated by the formation of colonic goblet cell associated
passages (GAPs), a pathway also known to deliver luminal antigens to antigen presenting cells (APCs) in the
lamina propria (LP) for the induction of T cell responses in the MLN. However, which bacteria the immune
system is responding to during stress and whether this immune response contributes to dysbiosis and
symptoms remains a significant gap in our understanding of stress as a trigger for flares of IBD and
IBS. We hypothesize that dysbiosis of the gut microbiota following stress allows for the translocation and
adaptive immune responses to specific bacterial taxa which serves to perpetuate dysbiosis and contribute to
stress induced GI symptoms. To pursue this hypothesis, we propose the following specific aims:
Aim 1. Define the taxa and pathways involved in bacterial translocation (BT) following stress, and how
that relates to the changes in the luminal microbiota.
Aim 2. Define the gut bacterial antigen specific immune response to stress induced dysbiosis and BT
Aim 3. Define the requirement of immune responses to commensal bacteria and the loss of gut
bacterial taxa following stress in inducing and maintaining dysbiosis and GI symptoms

## Key facts

- **NIH application ID:** 9947890
- **Project number:** 5R01AI140755-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** CHYI S HSIEH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $701,408
- **Award type:** 5
- **Project period:** 2018-07-18 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947890

## Citation

> US National Institutes of Health, RePORTER application 9947890, ROLE OF STRESS IN GUT IMMUNE INTERACTIONS WITH COMMENSAL BACTERIA (5R01AI140755-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9947890. Licensed CC0.

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