# Diet transformation by the microbiome and its impact on bacterial infection

> **NIH NIH R01** · YALE UNIVERSITY · 2023 · $834,833

## Abstract

Project Summary
Food contains a vast collection of bioactive small molecules that encounter enormous populations of
commensal microbes in the gastrointestinal tract. Microbiome metabolism has been reported across dietary
compound classes; however, the microbial enzymes that metabolize dietary small molecules can be highly
substrate specific and these activities can vary widely between individuals. The impact of diet on the
microbiome is also well established. Thus, the gut microbiome is likely a determining factor in an individual's
dietary metabolite exposure, with implications for infection, cancer, inflammatory diseases, cardiovascular
diseases, and other diseases impacted by diet. Microbes and diet directly intersect in the context of infections
caused by the food-borne enteropathogens Salmonella enterica serovar Typhimurium and Campylobacter
jejuni, which cause tens of millions of cases of food-borne illness every year, largely through consumption of
chicken and other poultry products. Progress understanding these interactions would transform our ability to
manage this major public health challenge, enabling interventions in humans and in our food chain where diet
can be directly prescribed. This proposal will test the hypothesis that modification of dietary compounds by the
gut microbiota, and disruption of the microbiota by dietary compounds, determines the function of these
molecules in modulating colonization resistance (pathogen exclusion by the microbiome), pathogen growth,
and virulence in humans and in our food chain. In Aim 1, we will generate a systematic map of the metabolism
of over 100 dietary compounds by over 100 gut microbes and microbiomes from two human cohorts and
chickens at the level of communities, species, enzymes, and metabolites. In Aim 2, we will determine how
these compounds modulate colonization resistance in gnotobiotic mouse and gnotobiotic chicken models of S.
Typhimurium and C. jejuni infections. In Aim 3, we will measure how dietary compounds and their microbial
metabolites impact pathogen growth and virulence in vitro, in 2D monolayers derived from intestinal organoids,
and in gnotobiotic animals. Together, these studies will define how the reciprocal interactions between diet and
the microbiome determine the outcome of food-borne infections, a major public health risk.

## Key facts

- **NIH application ID:** 10684849
- **Project number:** 5R01DK133798-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Jorge E Galan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $834,833
- **Award type:** 5
- **Project period:** 2022-08-16 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10684849

## Citation

> US National Institutes of Health, RePORTER application 10684849, Diet transformation by the microbiome and its impact on bacterial infection (5R01DK133798-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10684849. Licensed CC0.

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