# Bacteriophage pathobiology of inflammatory bowel disease

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $634,821

## Abstract

Bacteriophage pathobiology of inflammatory bowel disease
Ulcerative colitis and Crohn’s disease are types of inflammatory bowels diseases (IBD) that affect millions of
people around the world. IBD is characterized by chronic progressive intestinal inflammation which is driven in
large part by disruption of the gut microbiome in susceptible individuals. Infection by pathogens such as adherent
invasive Escherichia coli (AIEC) in particular exacerbates IBD pathogenesis. Treatment strategies that restore
gut microbiota homeostasis such as probiotics and fecal microbiota transplantation show promise in treating IBD.
These treatment strategies, however, focus primarily on the bacterial component of the microbiota. The most
abundant entities in the gut are the bacteriophages (phages) that infect these bacteria. Even though it is
recognized that phage populations expand during IBD exacerbations, we know surprisingly little about how
phages contribute to IBD pathogenesis. Our recent work demonstrates that diverse species of phages are
recognized by pattern recognition receptors on human and murine immune cells. We find filamentous phages
trigger TLR3-dependent inflammatory responses that promote bacterial infection in a wound infection model.
Vaccinating against these phages was an effective strategy at preventing wound infection. We also find that
tailed Caudovirales phages stimulate TLR9-dependent inflammation in the gut. Based on these observations,
we hypothesize that phages produced by adherent invasive E. coli modulate immune responses in ways that
exacerbate IBD. To test this hypothesis, we have established a team of microbiologists, immunologists, and
vaccine scientists. In Aim 1, we will characterize how inflammatory conditions stimulate bacteriophage replication
in the gut. In Aim 2, we will determine how broadly bacteriophages are recognized by innate pattern recognition
receptors. In Aim 3, we will develop and optimize an anti-bacteriophage vaccine strategy to treat IBD. Together,
these aims represent a novel and timely approach in understanding not only how phages affect IBD
pathogenesis, but for evaluating the safety and efficacy of phage therapy to treat multidrug-resistant bacterial
infections.

## Key facts

- **NIH application ID:** 10159896
- **Project number:** 5R01DK124317-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** June Louise Round
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $634,821
- **Award type:** 5
- **Project period:** 2020-05-06 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159896

## Citation

> US National Institutes of Health, RePORTER application 10159896, Bacteriophage pathobiology of inflammatory bowel disease (5R01DK124317-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159896. Licensed CC0.

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