# Small intestinal PepT1 expression plays a critical role in maintaining intestinal homeostasis and in shaping the gut microbiota

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

PepT1, which is a member of the proton oligopeptide transporter (POT) superfamily, is well known to
transport di/tripeptides. Our group and others have shown that PepT1 is highly expressed in epithelial cells of
the small intestine, but present at low or undetectable levels in such cells of the normal large intestine (1-8).
We previously showed that the expression and transport activities of PepT1 contribute to colitis and colitis
associated cancer (5, 9). More recently, we reported that the function of this membrane transporter is not
restricted to its classical function as transporter of di-tripeptides. For example, we demonstrated that PepT1
expression helps maintain intestinal homeostasis by mediating intestinal miRNA expression/secretion (10, 48).
Together, our prior studies revealed that PepT1 may be associated with intestinal homeostasis and implicated
in various pathogeneses, including those of colitis and colitis associated cancer. Our novel overall hypothesis
is that small intestinal PepT1 expression plays a critical role in maintaining intestinal homeostasis and in
shaping the gut microbiota. The initial aim of this proposal is to demonstrate that a lack of small intestinal
PepT1 expression shapes the gut microbiota into an anti-inflammatory microbiota that is implicated in
preventing colitis and colitis associated cancer. We will then explore the effects of small intestinal PepT1
expression and consequently the intestinal miRNA dysregulation on the intestinal mucosal homeostasis.
Finally, we will investigate how the microbiota is regulated by the expression/secretion of host miRNAs that
depend on the expression of PepT1 in the small intestine, and we will define ways to manipulate the
microbiome by administering specific miRNAs. We envisage that the planned work will identify the role played
by small intestinal PepT1 expression plays a critical role in maintaining intestinal homeostasis and in shaping
the gut microbiota. The proposed research will also facilitate the development of therapeutic strategies
targeting intestinal inflammatory conditions.

## Key facts

- **NIH application ID:** 9933792
- **Project number:** 5I01BX002526-07
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** DIDIER MERLIN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2014-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933792

## Citation

> US National Institutes of Health, RePORTER application 9933792, Small intestinal PepT1 expression plays a critical role in maintaining intestinal homeostasis and in shaping the gut microbiota (5I01BX002526-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933792. Licensed CC0.

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