# Regulation of enteric norovirus infection by host-derived and microbiota-transformed bile acids

> **NIH NIH R56** · UNIVERSITY OF FLORIDA · 2024 · $642,669

## Abstract

PROJECT SUMMARY
Noroviruses are the leading global cause of acute gastroenteritis, responsible for 685 million total
cases, 200 million pediatric cases, and up to 200,000 deaths in children annually. The long-term
goal of this research project is to define the mechanisms by which intestinal microbiota influence
norovirus pathogenesis and host immunity, and thus identify critical targets for novel therapeutics.
Bile acids are a class of metabolites regulated by microbiota that play opposing roles in norovirus
infections: Host-derived bile acids promote human and murine norovirus infections whereas
microbiota-derived bile acids inhibit infection. Considering that neonates are more susceptible to
norovirus infections and they have a distinct bile acid pool compared to adults that is dominated
by host-derived (proviral) species, our central hypothesis is that altered homeostatic bile acid
metabolism is the central determinant of the increased vulnerability of neonates to norovirus
disease. This will be tested by pursuing three specific aims: 1) Test the effect of perturbing the
neonatal bile acid pool on norovirus disease; 2) Determine the mechanism by which microbiota-
metabolized bile acids protect neonates from norovirus disease; and 3) Determine the role of
maternal breast milk bile acids in regulating neonatal susceptibility to norovirus diarrhea. The
proposed research is significant because it will provide mechanistic insight into the role of bile
acid metabolism in norovirus pathogenesis and test therapeutic strategies to reduce disease
severity in infected infants based on this insight. Our studies will also explore the innovative
concept that maternal gut metabolites delivered to neonates via breastfeeding determine neonatal
susceptibility to norovirus diarrhea, laying the groundwork for developing novel infant-specific
therapeutics that target the entero-mammary pathway in the lactating mother. Finally, bile acids
are being increasingly recognized as contributing to other pathologic conditions so understanding
basic aspects of their metabolism and trafficking in the mammalian host has broad applicability.

## Key facts

- **NIH application ID:** 11125012
- **Project number:** 2R56AI141478-06A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Stephanie M Karst
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $642,669
- **Award type:** 2
- **Project period:** 2018-11-25 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11125012

## Citation

> US National Institutes of Health, RePORTER application 11125012, Regulation of enteric norovirus infection by host-derived and microbiota-transformed bile acids (2R56AI141478-06A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11125012. Licensed CC0.

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