# Effect of Microbial Metabolites on Growth of Cryptosporidium

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $670,711

## Abstract

Summary
Cryptosporidiosis is a common cause of severe, chronic diarrheal disease in immunocompromised patients
such as those with HIV/AIDS. The only FDA approved drug for treatment of cryptosporidiosis, nitazoxanide,
has limited effectiveness in immunocompromised patients. Despite the advent of HAART therapy,
cryptosporidiosis still presents a major problem among patient populations where HIV diagnosis or anti-viral
treatments are inadequate. As an enteric pathogen, Cryptosporidium interacts with the complex microbial
community that constitutes the microbiome. Perturbations to the microbiota, such as through antibiotic
treatment, are associated with increased susceptibility to infection in adult animals. Additionally, neonatal
animals, which harbor an immature microbiota, are much more susceptible to Cryptosporidium infection than
adults. One method by which the microbiota may influence susceptibility to Cryptosporidium infection is
through the production of inhibitory small molecule metabolites. For example, high fecal indole levels were
associated with lower susceptibility in a human challenge study of Cryptosporidium. Collectively, these findings
raise the intriguing hypothesis that metabolites produced by the microbiota influence susceptibility to infection
with Cryptosporidium. In preliminary studies, we have screened a library of bacterial metabolites that are
abundant components of the normal adult microbiota for their ability to inhibit growth of C. parvum in vitro. We
identified several classes of metabolites that are potent inhibitors of parasite growth at levels that are not toxic
to host cells. The proposed studies will explore the mechanism(s) of inhibition by these microbial metabolites
by determining which stage(s) of the parasite life cycle they target and whether they are static or cidal. We will
also explore host cell signaling pathways that activate host defenses, as the potential mechanism by which
these metabolites act. Finally, by employing animal models for cryptosporidiosis, we will test whether inhibitory
metabolites can be used to treat infection in vivo. If successful, these studies may establish a new paradigm for
treating persistent cryptosporidiosis in immunocompromised patients.

## Key facts

- **NIH application ID:** 10070569
- **Project number:** 5R01AI145496-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** L. David Sibley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $670,711
- **Award type:** 5
- **Project period:** 2019-12-13 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070569

## Citation

> US National Institutes of Health, RePORTER application 10070569, Effect of Microbial Metabolites on Growth of Cryptosporidium (5R01AI145496-02). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/10070569. Licensed CC0.

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