# The role of FMO5 to maintain mucosal barrier integrity in the mouse colon

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $39,531

## Abstract

Project Summary/Abstract
The ability of an organism to cope with environmental and physiological stress is essential to sustain life.
Failure to appropriately respond to stress can lead to cellular damage, loss of organ function, development of
disease, and shortened lifespan. The gastrointestinal (GI) tract exhibits complex and extensive defense
mechanisms that are critical for maintaining intestinal integrity and function. The intestine plays a key role in
metabolism, nutrient and water absorption, and provides both physical and immunological defense against
dietary and luminal antigens. Dysfunctional intestinal barriers are a defining characteristic of inflammatory
bowel disease (IBD). While many studies have characterized how intestinal barriers fail during IBD,
identification of the stimuli and cellular mechanisms responsible for IBD remain elusive. This project focuses on
the interplay between the flavin-containing monooxygenase (FMO) enzyme family and intestinal barrier
integrity and function. FMOs are a family of enzymes involved in xenobiotic and endogenous metabolism. Our
previous work defined nematode FMO-2 as both necessary and sufficient to preserve health and longevity
during hypoxic, nutrient, and pathogenic stress. We now expand these studies to focus on mammalian models
of intestinal stress resistance, and our initial results suggest that the mammalian homolog of Cefmo-2, FMO5,
plays an essential role in maintaining intestinal homeostasis. Having generated an intestine-specific,
tamoxifen-inducible Fmo5 KO mouse line, our primary goal is to understand the interplay between FMO5 and
the mammalian intestine. We will achieve this goal by 1. mapping the complex interactions between the
development and maintenance of the mucosal barrier in FMO5 KO animals, 2. assessing the structural
durability of the intestinal epithelial lining when Fmo5 is acutely removed from the system, and 3. defining how
alterations in Fmo5 levels contribute to the chronic development of IBD. We will use cutting edge techniques in
combination with common physiological measures to understand the role of Fmo5 in the mammalian gut. The
results will identify how Fmo5 modifies physiological aspects including 1) goblet cell development, 2) crypt
metabolism and its contribution to goblet cell dysfunction, 3) mucosal barrier function and 4) the pathogenesis
of IBD. The resulting data will be lead toward understanding the molecular cause of mucosal barrier
dysfunction and will investigate, for the first time, Fmo5 action in the context of IBD. Together, this work will
define the role and necessity of Fmo5, a previously unknown player in intestinal health maintenance, in
regulating intestinal barrier formation and resistance to inflammatory disease. The completion of this project
will identify key mechanisms regulating the onset of GI disease and reveal potential mechanistic targets for
future therapeutic efforts to improve human health.

## Key facts

- **NIH application ID:** 10536947
- **Project number:** 1F31DK134183-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Megan Lynn Schaller
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $39,531
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10536947

## Citation

> US National Institutes of Health, RePORTER application 10536947, The role of FMO5 to maintain mucosal barrier integrity in the mouse colon (1F31DK134183-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10536947. Licensed CC0.

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