# Microbiome-derived small molecules and host resistance against Vibrio cholerae

> **NIH NIH P20** · UNIVERSITY OF KANSAS LAWRENCE · 2024 · $140,895

## Abstract

The human body is colonized by a complex microbial community with critical roles for health. This microbiota 
educates the immune system, helps digest our food, and protects us against pathogens. The diversity of 
microbes and encoded functions is significant. Our group showed that the gut microbiota is also a source of 
great chemical diversity, and that most of the compounds produced are unknown. Bacteria produce and 
respond to small molecules to communicate and adapt to their environment. Chemical signaling controls 
functions that are critical for host adaptation in most pathogens. Therefore, small-molecule signaling is an 
attractive target for the development of anti-infectives. Given the chemical complexity of the gut, microbiotapathogen 
crosstalk must be common. In fact, we previously showed that an organic extract of human feces 
elicits a significant transcriptional response in Salmonella enterica, with ~100 regulated genes. Interestingly, 
virulence genes were abundant among those repressed by the extract, suggesting that microbiota-derived 
metabolites can dampen virulence. We then determined that a single commensal, Enterocloster citroniae, 
can repress S. enterica virulence gene expression. More recently, we studied the transcriptional impact of 
the human fecal metabolome on other pathogens. In Vibrio cholerae, the causative agent of cholera, the 
effect was even more pronounced, with ~900 genes being regulated. Motility was the main category of 
repressed genes, and the effect was confirmed by phenotypic assays. As with S. enterica, the effect could 
be recapitulated with E. citroniae. Given the importance of V. cholerae as a human pathogen and the critical 
role played by motility in its pathogenesis, it is our goal to determine the impact of microbiota-derived 
metabolites on V. cholerae pathogenicity. We will generate a collection of gut commensals with anti-motility 
properties to characterize the genetic and chemical nature of the bioactivity. Genomes and transcriptomes 
of active and inactive strains will be compared, giving insights into the synthetic apparatus involved. 
Bioactivity-guided purification will be performed, and compound characterization using mass spectrometry 
and nuclear magnetic resonance will ensue. Lastly, we will study the impact of active strains and compounds 
on host resistance to V. cholerae using infection models. Results from this work will shed light on the chemical 
biology of microbiota-pathogen interactions and may reveal strains and compounds with potential therapeutic 
applications.

## Key facts

- **NIH application ID:** 10870109
- **Project number:** 5P20GM113117-09
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **Principal Investigator:** Luis Caetano Martha Antunes
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $140,895
- **Award type:** 5
- **Project period:** 2016-05-15 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870109

## Citation

> US National Institutes of Health, RePORTER application 10870109, Microbiome-derived small molecules and host resistance against Vibrio cholerae (5P20GM113117-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10870109. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*