Abstract
Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of RV deaths occur in Africa and Asia where rotavirus vaccines (RVV) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. Methods. We conducted a nested, case-control study comparing pre-vaccination, fecal microbiome compositions between 6-week old, matched RVV-responders and non-responders in rural Ghana. These infants' microbiomes were then compared to 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV-responders. Fecal microbiota analysis was performed in all groups using the Human Intestinal Tract Chip (HITChip). Results. 78 Ghanaian infants, equalling 39 RVV responder and non-responder pairs, were analysed. The overall microbiome composition was significantly different between RVV-responders and non-responders (FDR=0.12), and Ghanaian responders were more similar to Dutch infants than non-responders (p=0.002). RVV-response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between Ghanaian RVV-responders and non-responders (FDR=0.008, FDR=0.003) as well as between Dutch infants and Ghanaian non-responders (FDR=0.002, FDR=0.009). Conclusions. The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
