# Metabolic And Spatial Competition For Dietary Fiber Between Commensal And Pathogenic Gut Microbes

> **NIH NIH K01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2022 · $162,205

## Abstract

PROJECT SUMMARY
The microbial community that resides in the human intestine profoundly influences host metabolism, immune
homeostasis, and the outcome of enteric infections. Dietary fiber is a promising tool for manipulating the gut
microbiota to promote organisms that provide beneficial functions to the host. Though, it is currently difficult to
predict which gut bacterial species will respond to fiber-based dietary interventions, interspecies competition
makes it possible to precisely target beneficial species of interest using a particular fiber type. Bacterial species
with pathogenic potential, such as uropathogenic E. coli (UPEC), are present in the gut microbiota of
asymptomatic individuals and these species have the capacity to expand in response to fiber. Exploiting
competition between pathogens and their non-pathogenic relatives to reduce pathogen load in the gut will
require detailed knowledge of the genes underlying these species’ overlapping nutrient harvesting strategies,
including genes mediating adhesion to nutrient-rich diet-derived particles. The following aims will test the
hypotheses that (i) expansion of commensal E. coli in the gut in response to dietary fiber can reduce the fitness
of pathogenic E. coli, and that (ii) commensal and pathogenic bacterial species compete for adhesion to the
same diet-derived surfaces in the intestinal lumen. In Aim1, I will identify dietary fibers that selectively increase
the abundance of commensal E. coli in vivo. Preliminary studies have identified a widely consumed fiber that
increases the abundance of commensal E. coli in a model microbial community. I will define the mechanism of
action by colonizing these mice with an E. coli transposon mutant library and performing community-wide
quantitative proteomics and forward genetic analyses. To model a gut reservoir of pathogenic E. coli, I will
substitute UPEC for commensal E. coli in this community, and then administer commensal E. coli with or
without fiber to identify interventions that reduce UPEC abundance. In Aim2, I will determine whether
commensal and pathogenic microbes adhere to the same surfaces in the gut. A multiplex adhesion assay,
using glycan-coated magnetic beads, identified dietary fibers that support adhesion of both UPEC and
commensal E. coli. I will validate adhesive interactions in vivo by administering these particles to mice and
measuring bacterial localization around beads in situ. Application of the bead-based adhesion assay to cecal
microbiota of mice colonized with uncultured human fecal samples will identify additional E. coli strains, as well
as uncharacterized gut microbes, that adhere to dietary glycans in vivo. This research will (i) provide insights
into the ecological relationships that determine the outcome of dietary interventions designed to promote
beneficial species at the expense of known pathogens and ii) provide candidate dietary components, bacterial
strains, and microbial genetic targets for manipula...

## Key facts

- **NIH application ID:** 10327331
- **Project number:** 5K01DK124445-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Michael L Patnode
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $162,205
- **Award type:** 5
- **Project period:** 2020-04-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10327331

## Citation

> US National Institutes of Health, RePORTER application 10327331, Metabolic And Spatial Competition For Dietary Fiber Between Commensal And Pathogenic Gut Microbes (5K01DK124445-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10327331. Licensed CC0.

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