Klebsiella-dominant gut communities are associated with impeded oral rotavirus vaccine response in infants

Abstract Rotavirus gastroenteritis is the leading cause of infant diarrheal death worldwide. Oral rotavirus vaccine (RVV) prevents illness and death, but efficacy differs between high- and low-income countries and the etiologies are unclear. Here, we describe the relationship between colonization of the infant gut by commensal bacteria, inflammation, and vaccine response across a cohort of infants from Panama, Peru, and the U.S. Vaccine immunogenicity was related to community composition in the first month of life and inverse to increased relative abundance of Klebsiella . Clustering communities into gut types revealed that microbiome configurations with elevated Klebsiella or Escherichia in the first month of life were negatively associated with both seroconversion and rotavirus shedding after vaccination, suggesting potential inhibition of vaccine function or host response. Infants without RVV strain shedding displayed elevated fecal calprotectin in the first month. These results implicate microbiome-augmented infant gut inflammation as a potential impediment to RVV response.