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

Oral rotavirus vaccine immunogenicity was related to gut microbiome community composition in the first month of life.

• The study enrolled infants from three countries: Panama, Peru, and the U.S.
• Vaccine immunogenicity was assessed across this multinational cohort.
• Community composition in the first month of life was identified as relevant to vaccine response.
• The relationship was observed across geographically and economically diverse settings.

Increased relative abundance of Klebsiella in the first month of life was inversely associated with oral rotavirus vaccine immunogenicity.

• Higher relative abundance of Klebsiella was associated with reduced vaccine immunogenicity.
• The association was observed specifically in the first month of life.
• This finding was identified across the multinational cohort spanning Panama, Peru, and the U.S.
• The inverse relationship suggests Klebsiella colonization may interfere with vaccine function or host immune response.

Gut microbiome configurations with elevated Klebsiella or Escherichia in the first month of life were negatively associated with both seroconversion and rotavirus shedding after vaccination.

• Gut communities were clustered into 'gut types' based on microbiome configurations.
• Both seroconversion (immune response measure) and rotavirus shedding (measure of vaccine virus replication) were negatively associated with Klebsiella- or Escherichia-dominant gut types.
• The dual association with seroconversion and shedding suggests potential inhibition at the level of vaccine virus replication and/or host immune response.
• The analysis focused on microbiome profiles from the first month of life, prior to or early in the vaccination window.

Infants without rotavirus vaccine strain shedding displayed elevated fecal calprotectin in the first month of life.

• Fecal calprotectin is a marker of gut inflammation.
• Infants who did not shed the rotavirus vaccine strain had higher fecal calprotectin levels compared to those who did shed.
• Elevated calprotectin was observed in the first month of life, suggesting pre-existing or early gut inflammation.
• This finding links gut inflammation to impaired vaccine virus replication as measured by shedding.

The authors implicate microbiome-augmented infant gut inflammation as a potential impediment to oral rotavirus vaccine response.

• The combination of Klebsiella/Escherichia-dominant gut types and elevated fecal calprotectin suggests a mechanistic link between gut microbiome composition, inflammation, and vaccine failure.
• The findings are framed as identifying 'microbiome-augmented infant gut inflammation' as the potential pathway of impairment.
• This provides a potential explanation for differential vaccine efficacy observed between high- and low-income countries.
• The study describes the relationship as a potential mechanism rather than a confirmed causal pathway.

Rotavirus vaccine efficacy differs between high- and low-income countries and the etiologies have been unclear prior to this study.

• The authors describe rotavirus gastroenteritis as 'the leading cause of infant diarrheal death worldwide.'
• Oral rotavirus vaccine prevents illness and death but has differential efficacy across income settings.
• The study was designed in part to investigate these unexplained differences in vaccine performance.
• The multinational cohort from Panama, Peru, and the U.S. was chosen to span different income and epidemiological contexts.