# PepT1-/- microbiota therapy as a treatment for colitis

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2023 · —

## 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. In
addition, we have demonstrated that colonic PepT1 expression is up-regulated in colitis and colitis-associated
cancer (CAC). By generating gain- and loss-of-function mouse models with PepT1 expression specifically in
intestinal epithelial cells (IECs), we explored the role of PepT1 in intestinal homeostasis, inflammation, and
colitis-associated tumorigenesis. We also examined the expression and transport activities of PepT1, using
mouse models of colitis and CAC, and further revealed that the function of this membrane transporter is not
restricted to its classical function as a transporter of di-tripeptides. For example, we demonstrated that PepT1
expression helps maintain intestinal homeostasis by mediating intestinal miRNA expression/secretion.
Importantly we demonstrated during the last funding cycle that the PepT1-/- microbiota/metabolome is sufficient
to protect against colitis and CAC. The overall goal of the current proposal is to develop a drug delivery
platform to treat colitis. The initial aim of this proposal will be to investigate whether oral delivery of alginate
hydrogel-loaded PepT1-/- microbiota will enhance the engraftment dynamics/diversity of the donor microbiota
and consequently enhance the prevention/treatment of colitis. In the second aim, we will explore the cellular
targets of PepT1-/- microbiota and assess the subsequent intestinal cellular responses that decrease colitis.
Finally, we will characterize and assess the in vivo colitis-preventing effects of oral administration of specific
anti-inflammatory metabolites from PepT1-/- microbiota loaded into nanoparticles. The proposed research will
facilitate the development of therapeutic solutions targeting intestinal inflammatory and colitis associated
cancer conditions.

## Key facts

- **NIH application ID:** 10655304
- **Project number:** 5I01BX002526-10
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** DIDIER MERLIN
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2014-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10655304

## Citation

> US National Institutes of Health, RePORTER application 10655304, PepT1-/- microbiota therapy as a treatment for colitis (5I01BX002526-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10655304. Licensed CC0.

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