|HUDA, M - University Of California|
|LEWIS, Z - University Of California|
|KALANETRA, K - University Of California|
|RASHID, M - International Centre For Diarrhoeal Disease Research|
|RAQIB, R - International Centre For Diarrhoeal Disease Research|
|QADRI, F - International Centre For Diarrhoeal Disease Research|
|UNDERWOOD, M - University Of California|
|MILLS, D - University Of California|
Submitted to: Pediatrics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2014
Publication Date: 8/1/2014
Citation: Huda, M.N., Lewis, Z., Kalanetra, K.M., Rashid, M.N., Raqib, R., Qadri, F., Underwood, M.A., Mills, D.A., Stephensen, C.B. 2014. Stool microbiota and vaccine responses of infants. Pediatrics. 134:1-11. DOI: 10.1542/peds.2013-3937.
Interpretive Summary: Infant vaccine responses can be low in less-developed countries in association with environmental enteropathy. Characterizing the intestinal microbiota with new DNA methods allows examination of changes in this microbial community as a predictor of vaccine responses. This study reports that a high abundance of Bifidobacterium and low bacterial diversity in the stool of breastfed Bangladeshi infants at 15 wk of age was associated with better responses to the oral polio virus, Bacillus Calmette–Guérin and tetanus toxoid vaccines. These data suggest that a reason for poor vaccine responses in less-developed countries may be the over-representation of non-beneficial intestinal bacteria.
Technical Abstract: Objective: Vaccination decreases morbidity and mortality. Vaccine efficacy may be lower in less-developed countries due to environmental enteropathy. This study determined if relative abundance of stool bacteria predicted infant vaccine responses. Methods: The stool microbiome of 48 breastfed Bangladeshi infants was characterized with DNA methods at 6, 10 and 15 wk of age. All infants received standard vaccines at birth (oral polio virus [OPV] and Bacillus Calmette–Guérin [BCG]) and at 6, 10 and 14 wk of age (OPV, Diphtheria-Pertussis-Tetanus [DPT] and hepatitis B virus [HBV]). Vaccine responsiveness was assessed using proliferative responses to vaccine antigens (OPV, PPD [a component of BCG], TT and HBV), and delayed-type hypersensitivity (DTH) skin-test response to PPD, at 15 wk of age. Thymus size was measured by ultrasound. Results: Actinobacteria (predominantly Bifidobacterium longum subspecies infantis) dominated the microbiota with Proteobacteria and Firmicutes increasing by 15 wk in association with supplemental feeding to increase bacterial diversity. Actinobacteria and Bifidobacterium abundance at 15 wk were positively associated with T-cell responses to PPD, OPV and TT, with the PPD-DTH response and with thymic index. Some Gammaproteobacteria were associated with greater diversity, neutrophilia and lower vaccine responses. Discussion: Bifidobacterium predominance may enhance thymic development and responses to T-cell dependent vaccines early in infancy while deviation from this pattern results in greater diversity and perhaps inflammation causing lower vaccine responses. Conclusions: Vaccine responsiveness might improve by promoting intestinal Bifidobacteria and limiting bacterial diversity early in infancy.