# Impact of Microbiota-Generated Metabolites on Campylobacter jejuni Colonization

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2021 · $413,843

## Abstract

Project Summary
To infect a host, bacteria must recognize niches that support growth and interact or compete with members of
the microbiota to establish residence in a niche to promote disease or persistence. Campylobacter jejuni is a
leading cause of bacterial diarrheal disease in the United States and throughout the world. C. jejuni is also a
commensal bacterium of the intestinal tracts of many animals in the wild and agriculture, especially avian
species. Sporadic cases of C. jejuni diarrheal disease are most often associated with consumption or handling
of contaminated chicken meats. Thus, understanding mechanisms for how C. jejuni senses and responds to
avian or human intestinal components during initial events in infection are useful for developing therapeutic
strategies that may reduce the burden of C. jejuni diarrheal disease in humans and the presence of the
bacterium in agriculture and meats for human consumption. We discovered that C. jejuni senses and responds
to metabolites generated by the intestinal microbiota of chickens to influence expression of genes essential for
commensal colonization of avian hosts, with some genes also functioning in pathogenesis of diarrheal disease
in humans. We found that short-chain fatty acids (SCFAs) such as butyrate and acetate that are abundant in
the lower intestinal tract, stimulated expression of many genes required for colonization of chicks. In contrast,
the organic acid lactate, which is produced at higher levels in the upper intestinal tract, repressed expression of
these same genes. We propose that C. jejuni senses SCFAs and organic acids produced by the resident
microbiota to discriminate between different intestinal regions and identify lower intestinal niches that are ideal
to support in vivo growth to establish a persistent, commensal colonization of the intestines of poultry. Since
the metabolites and microbiota species that produce them are similarly spatially organized in the human
intestines, we propose that C. jejuni monitors the same metabolites to identify ideal human colonic niches that
support growth to establish an infection for diarrheal disease. In Aim 1, we will explore the C. jejuni SCFA- and
lactate-modulated regulon and identify new colonization determinants of C. jejuni. In Aim 2, we will employ
multiple approaches to identify pathways in C. jejuni involved in sensing SCFAs and lactate and mediating
expression of colonization and virulence genes. In Aim 3, we will explore how in vivo manipulation of SCFAs
and lactate levels or the microbiota that generate them impacts C. jejuni for commensal colonization of the
avian intestines. Accomplishment of these aims will promote new insights for: 1) how C. jejuni senses and
responds to in vivo metabolites and factors to recognize ideal niches for establishing infection; 2) factors
required for C. jejuni colonization and virulence; 3) regulatory mechanisms for C. jejuni gene expression; 4)
how manipulation of the human or avian in...

## Key facts

- **NIH application ID:** 10179434
- **Project number:** 5R01HD095830-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** DAVID R HENDRIXSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $413,843
- **Award type:** 5
- **Project period:** 2019-08-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10179434

## Citation

> US National Institutes of Health, RePORTER application 10179434, Impact of Microbiota-Generated Metabolites on Campylobacter jejuni Colonization (5R01HD095830-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10179434. Licensed CC0.

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