The fecal microbiome and rotavirus vaccine immunogenicity in rural Zimbabwean infants

Abstract

Background Oral rotavirus vaccine (RVV) immunogenicity is considerably lower in low- versus high-income populations; however, the mechanisms underlying this remain unclear. Previous evidence suggests that the gut microbiota may contribute to differences in oral vaccine efficacy. Methods We performed whole metagenome shotgun sequencing on stool samples and measured anti-rotavirus immunoglobulin A in plasma samples from a subset of infants enrolled in a cluster randomized 2 × 2 factorial trial of improved water, sanitation and hygiene and infant feeding in rural Zimbabwe (SHINE trial: NCT01824940). We examined taxonomic microbiome composition and functional metagenome features using random forest models, differential abundance testing and regression analyses to explored associations with RVV immunogenicity. Results Among 158 infants with stool samples and anti-rotavirus IgA titres, 34 were RVV seroconverters. The median age at stool collection was 43 days (IQR: 35–68), corresponding to a median of 4 days before the first RVV dose. The infant microbiome was dominated by Bifidobacterium longum . The gut microbiome differed significantly between early (≤42 days) and later samples (>42 days) however, we observed no meaningful differences in alpha diversity, beta diversity, species composition or functional metagenomic features by RVV seroconversion status. Bacteroides thetaiotaomicron was the only species associated with anti-rotavirus IgA titre. Random forest models poorly classified seroconversion status by both composition and functional microbiome variables. Conclusions RVV immunogenicity is low in this rural Zimbabwean setting, however it was not associated with the composition or function of the early-life gut microbiome in this study. Further research is warranted to examine the mechanisms of poor oral RVV efficacy in low-income countries.

Intestinal Colonization With Bifidobacterium longum Subspecies Is Associated With Length at Birth, Exclusive Breastfeeding, and Decreased Risk of Enteric Virus Infections, but Not With Histo-Blood Group Antigens, Oral Vaccine Response or Later Growth in Three Birth Cohorts

“…These findings are consistent with the hypothesis that the infantis subspecies plays a role in the priming of early cellular immunity (7), however, this did not translate into a decrease in overall risk of diarrheal disease-indeed, this risk was slightly increased in subjects with higher B. infantis quantity. No clear associations between infantis colonization and humoral vaccine responses were detected, in contrast with previously published findings from Bangladesh (9), but in line with those for rotavirus vaccine immunogenicity in Zimbabwe (49). Furthermore, a slight increase in risk of Campylobacter jejuni/coli was observed for each log 10 increase in B. infantis quantity, in contrast to previous findings from a Peruvian cohort which found Bifidobacterium amplicon sequence variant abundance to be associated with slightly lower Campylobacter burden at 6 months of age (50).…”

The gut microbiome and early-life growth in a population with high prevalence of stunting

“…Of the mother-infant pairs within the EED sub-study, those with least one maternal fecal specimen (of 2 possible) and at least 2 infant fecal specimens (of 5 possible) were included in the gut microbiome analyses. An additional 94 samples collected at the 1 and 3-month visits, that did not meet these criteria, but had microbiome sequencing data available from a separate study examining rotavirus vaccine immunogenicity in the SHINE trial (59), were also included in these analyses. Infant ages varied at each study visit due to the allowable window around the visit date for the larger SHINE trial.…”

Vaccines, Microbiota and Immunonutrition: Food for Thought

“…Most studies focus on the impact of microbiota composition on orally administered vaccines, particularly oral rotavirus vaccine [112][113][114][115], yet vaccinations administered through the intramuscular route have also been influenced by microbiota composition. Influenza vaccination, for instance, seems to be more effective in those with Prevotella colonisation [116].…”

“…A general overview of the available recent literature on the topic [110][111][112][113][114][115][116][117][118][119][120] can be found in Table 1.…”