# Mechanisms of alteration of GI physiology by gut microbes

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2020 · $357,750

## Abstract

ABSTRACT
The overall goal of our laboratory's research is to
determine the mechanisms by which gut microbiota and their
products alter gastrointestinal (GI) tract luminal physiology and to
develop microbiota-based therapeutic
manipulations to correct altered physiology in diseases like irritable bowel syndrome (IBS) associated with
alterations in gut microbiota. Our preliminary studies have identified the gene tryptophan decarboxylase which
converts dietary tryptophan to tryptamine in common human gut commensal bacteria like Ruminococcus
gnavus and Clostridium sporogenes. Furthermore our preliminary data show that tryptamine increases short
circuit current (representing ionic flux; surrogate for secretion) across the colonic epithelium in vitro in Ussing
chamber studies and this effect can be inhibited by serotonin receptor4 (5HT4R) antagonists and is absent in
5HT4R knock out mice. Interestingly genetically engineered bacteria with the gene tryptophan decarboxylase
produce tryptamine in vivo in gnotobiotic mice and accelerate whole gut transit, when diet is supplemented with
tryptophan. Our overall hypothesis is that dietary tryptophan driven production of bacterial tryptamine increases
5HT4R-mediated intestinal secretion modulating GI function in health and disease. In order to determine the
mechanism of action of tryptamine we will first determine if the effect of exogenous tryptamine on intestinal
secretion is dependent on 5HT4R and identify specific downstream pathways responsible for secretion. We will
then investigate the effect of dietary tryptophan on bacteria produced tryptamine and 5HT4R mediated
intestinal secretion and whole gut transit as well as its application in a preclinical model of constipation. The
results from this study will potentially contribute to the development of novel engineered probiotics capable of
producing a bioactive metabolite such as tryptamine to correct the altered physiology such as constipation in
diseases like IBS.

## Key facts

- **NIH application ID:** 9990758
- **Project number:** 5R01DK114007-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Purna C Kashyap
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,750
- **Award type:** 5
- **Project period:** 2017-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990758

## Citation

> US National Institutes of Health, RePORTER application 9990758, Mechanisms of alteration of GI physiology by gut microbes (5R01DK114007-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9990758. Licensed CC0.

---

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