Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea,Cell Host & Microbe

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Metabolic immaturity and breastmilk bile acid metabolites are central determinants of heightened newborn vulnerability to norovirus diarrhea
Cell Host & Microbe ( IF 20.6 ) Pub Date : 2024-08-29 , DOI: 10.1016/j.chom.2024.08.003
Amy M Peiper ₁ , Joyce Morales Aparicio ₁ , Zhengzheng Hu ₁ , Lufuno Phophi ₁ , Emily W Helm ₁ , Rebecca J Rubinstein ₂ , Matthew Phillips ₁ , Caroline G Williams ₁ , Saravanan Subramanian ₃ , Michael Cross ₁ , Neha Iyer ₁ , Quyen Nguyen ₁ , Rachel Newsome ₄ , Christian Jobin ₄ , Stephanie N Langel ₅ , Filemon Bucardo ₆ , Sylvia Becker-Dreps ₂ , Xiao-Di Tan ₇ , Paul A Dawson ₈ , Stephanie M Karst ₁

Affiliation

Department of Molecular Genetics & Microbiology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Pediatric Mucosal Inflammation and Regeneration Research Program, Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
Department of Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
Department of Pathology, Center for Global Health and Diseases, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Department of Family Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Pediatric Mucosal Inflammation and Regeneration Research Program, Center for Pediatric Translational Research and Education, Department of Pediatrics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA; Department of Research & Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL 60612, USA.
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition, Emory School of Medicine, Atlanta, GA 30329, USA.

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.

中文翻译：

代谢不成熟和母乳胆汁酸代谢物是新生儿对诺如病毒腹泻易感性增加的核心决定因素

肠道病毒感染的致病结果由病毒、肠道微生物群和宿主免疫因子之间复杂的相互作用控制，其中代谢物是关键介质。诺如病毒结合胆汁酸代谢物，胆汁酸代谢物由宿主产生，然后被共生菌修饰。矛盾的是，在诺如病毒感染期间，胆汁酸可以同时具有促病毒和抗病毒作用。在诺如病毒感染的婴儿小鼠模型中工作，我们证明微生物群及其胆汁酸代谢物可防止诺如病毒腹泻，而宿主胆汁酸会促进疾病。我们还发现，母体胆汁酸代谢决定了新生小鼠在母乳喂养期间对诺如病毒腹泻的易感性。最后，靶向母体和新生儿胆汁酸代谢可以保护新生小鼠免受诺如病毒病的侵害。总之，新生儿代谢不成熟和母乳胆汁酸是新生儿对诺如病毒病易感性增加的核心决定因素。

更新日期：2024-08-29

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