# Exacerbation of Colitis by Enterobacteriaceae

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2023 · $452,573

## Abstract

ABSTRACT
 Ulcerative colitis is a complex disease caused by a combination of genetic risk factors,
childhood exposure to environmental risk factors and a poorly defined microbiota component.
Ulcerative colitis is associated with imbalance in the microbiota (dysbiosis) characterized by
increased Enterobacteriaceae and reduced Clostridia abundance. Ulcerative colitis can respond
to antibiotic treatment, which suggests that dysbiosis exacerbates intestinal inflammation, thus
raising the question as to how microbiota homeostasis can be restored. Our preliminary data
suggest that epithelial hypoxia and epithelial release of hydrogen peroxide represent host control
mechanisms that maintain homeostasis in the colon and that facultative anaerobic
Enterobacteriaceae exacerbates colitis when these host control mechanisms become weakened
by a combination of genetic and environmental risk factors. Our central hypothesis is that
increased epithelial oxygenation drives an expansion of facultative anaerobic Enterobacteriaceae
that exacerbate colitis because members of this family are not excluded by growth conditions
encountered in close proximity to the epithelial surface. In specific aim 1 we will test the working
hypothesis that rebalancing the gut microbiota by reinstating epithelial hypoxia represents a
feasible approach for restoring gut homeostasis. In specific aim 2 we will determine how
Enterobacteriaceae exacerbate colitis in mice carrying a genetic risk factor while being exposed
to a combination of environmental risk factors. Successful completion of the proposed work will
be of broad significance for research on microbial ecology in the gut, the dynamics of gut-
associated microbial communities during inflammation and the pathogenesis of ulcerative colitis.

## Key facts

- **NIH application ID:** 10595010
- **Project number:** 5R01AI112445-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Andreas J Baumler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $452,573
- **Award type:** 5
- **Project period:** 2015-01-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595010

## Citation

> US National Institutes of Health, RePORTER application 10595010, Exacerbation of Colitis by Enterobacteriaceae (5R01AI112445-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10595010. Licensed CC0.

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