Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea
The pathogenic outcome of enteric virus infections is governed by a complex interplay between the virus, intestinal microbiota, and host immune factors, with metabolites serving as a key mediator. Noroviruses bind bile acid metabolites, which are produced by the host and then modified by commensal bacteria. Paradoxically, bile acids can have both proviral and antiviral roles during norovirus infections. Working in an infant mouse model of norovirus infection, we demonstrate that microbiota and their bile acid metabolites protect from norovirus diarrhea, whereas host bile acids promote disease. We also find that maternal bile acid metabolism determines the susceptibility of newborn mice to norovirus diarrhea during breastfeeding. Finally, targeting maternal and neonatal bile acid metabolism can protect newborn mice from norovirus disease. In summary, neonatal metabolic immaturity and breastmilk bile acids are central determinants of heightened newborn vulnerability to norovirus disease.
Authors
- Emily W. Helm
- Sylvia Becker‐Dreps (ORCID: https://orcid.org/0000-0002-7808-2507)
- Stephanie M. Karst (ORCID: https://orcid.org/0000-0003-0406-4637)
- Quyen Nguyen
- Lufuno Phophi (ORCID: https://orcid.org/0000-0002-4378-2976)
- Rebecca Rubinstein (ORCID: https://orcid.org/0000-0001-8620-0959)
- Rachel C. Newsome (ORCID: https://orcid.org/0000-0003-4124-8339)
- Neha Iyer
- Stephanie N. Langel (ORCID: https://orcid.org/0000-0002-0467-7874)
- Caroline G. Williams (ORCID: https://orcid.org/0000-0002-1598-5688)
- Amy Peiper (ORCID: https://orcid.org/0000-0001-9291-5563)
- Christian Jobin (ORCID: https://orcid.org/0000-0002-3733-1001)
- Filemón Bucardo (ORCID: https://orcid.org/0000-0002-9819-870X)
- Saravanan Subramanian (ORCID: https://orcid.org/0000-0003-2502-9531)
- Matthew B. Phillips (ORCID: https://orcid.org/0000-0001-9241-1066)
- Paul A. Dawson (ORCID: https://orcid.org/0000-0001-9760-4422)
- Michael Cross (ORCID: https://orcid.org/0000-0002-0864-325X)
- Zhengzheng Hu
- Joyce Morales Aparicio
- Xiao‐Di Tan (ORCID: https://orcid.org/0000-0003-3766-5885)
Institutions
- Emory Healthcare (US)
- Emory University (US)
- University of Florida (US)
- University of Illinois Chicago (US)
- Case Western Reserve University (US)
Publication Details
- Journal
- Cell Host & Microbe
- Published
- 2024-08-29
- DOI
- https://doi.org/10.1016/j.chom.2024.08.003
- Citations
- 11
- Primary Topic
- Viral gastroenteritis research and epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 4.28
Funders
- U.S. Department of Veterans Affairs
- University of Florida
- Beckman Research Institute, City of Hope
- University of Illinois System
- National Institutes of Health
- University of Illinois at Urbana-Champaign
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases