# The role of host-derived reactive oxygen species in the outgrowth of Escherichia coli during non-infectious colitis

> **NIH NIH F31** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $11,827

## Abstract

Project Summary
Patients with Inflammatory Bowel Disease (IBD) experience relapsing and remitting periods of inflammation in
their gastrointestinal tract. During periods of inflammation, many patients exhibit an alteration in colonic microbial
communities resulting in an increase in facultative anaerobes (primarily members of the Enterobacteriaceae
family, such as E. coli). Similar changes in the gut microbiota composition are observed in murine models of
colitis. Previous work from our laboratory indicates that the expansion of the Enterobacteriaceae population can
be abrogated in part, by inhibiting two of the metabolic pathways utilized by these bacteria to outgrow during
inflammation. Inhibition of this Enterobacteriaceae bloom reduced gut inflammation. This finding suggests that
microbial dysbiosis aggravates inflammation leading to poorer host outcomes and supports the approach of
specifically targeting the microbiota as a means of ameliorating disease. The objective of this study is to further
elucidate the metabolic pathways utilized by facultative anaerobes to outgrow during inflammatory conditions.
My preliminary data suggest a counterintuitively positive relationship between host-derived reactive oxygen
species and the outgrowth of Enterobacteriaceae. I hypothesize that reactive oxygen species allow facultative
anaerobic Enterobacteriaceae to respire in the inflamed gut lumen. The specific aims of this proposal are to
(1) determine the contribution of host-derived reactive oxygen species in the outgrowth of E. coli in murine
models of colitis and (2) determine the mechanistic relationship between cytochrome bd-II oxidase (AppBC) and
reactive oxygen species in vitro. To test my hypotheses, I will use a strategic combination of host and bacterial
genetics in both chemically-induced and genetic models of colitis. Changes in oxygen metabolism will be
characterized using immunohistochemical staining, bacterial reporter strains, microelectrode-based technology,
and metagenomics. The potential impact of my research will be to understand how oxygen availability influences
Enterobacteriaceae outgrowth during inflammation and explore the role reactive oxygen species play in this
process. A positive outcome may lay the foundation for novel treatment strategies for IBD patients.
Additionally, the training plan I have laid out will help me achieve my goal of becoming an academic researcher
at a major university or hospital system. I will be mentored by my Spnosor Sebastian Winter, Ph.D., an expert in
host-microbe interactions during inflammation, and by my Co-Sponsor Vanessa Sperandio, Ph.D., an expert in
bacterial pathogenesis and gene regulation. Along with support from the Graduate School and Career
Development Office, Dr. Winter and Dr. Sperandio will help me attain and strengthen skills necessary for success
in academic research, including responsible conduct, technical expertise, and scientific communication skills.

## Key facts

- **NIH application ID:** 10128185
- **Project number:** 5F31DK121465-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Rachael Chanin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $11,827
- **Award type:** 5
- **Project period:** 2020-04-01 → 2021-06-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128185

## Citation

> US National Institutes of Health, RePORTER application 10128185, The role of host-derived reactive oxygen species in the outgrowth of Escherichia coli during non-infectious colitis (5F31DK121465-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10128185. Licensed CC0.

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