WHAT'S KNOWN ON THIS SUBJECT:Oral vaccine responses are low in children from less-developed countries perhaps as a result of intestinal dysbiosis. New high-throughput DNA-based methods allow characterization of intestinal microbiota as a predictor of vaccine responses.WHAT THIS STUDY ADDS: High abundance of stool Actinobacteria, including Bifidobacterium, was associated with higher responses to oral and parenteral vaccines and a larger thymus in Bangladeshi infants. Conversely, high abundance of Clostridiales, Enterobacteriales, and Pseudomonadales was associated with neutrophilia and lower vaccine responses. abstract OBJECTIVE: Oral vaccine efficacy is low in less-developed countries, perhaps due to intestinal dysbiosis. This study determined if stool microbiota composition predicted infant oral and parenteral vaccine responses. METHODS:The stool microbiota of 48 Bangladeshi infants was characterized at 6, 11, and 15 weeks of age by amplification and sequencing of the 16S ribosomal RNA gene V4 region and by Bifidobacterium-specific, quantitative polymerase chain reaction. Responses to oral polio virus (OPV), bacille Calmette-Guérin (BCG), tetanus toxoid (TT), and hepatitis B virus vaccines were measured at 15 weeks by using vaccine-specific T-cell proliferation for all vaccines, the delayed-type hypersensitivity skin-test response for BCG, and immunoglobulin G responses using the antibody in lymphocyte supernatant method for OPV, TT, and hepatitis B virus. Thymic index (TI) was measured by ultrasound.RESULTS: Actinobacteria (predominantly Bifidobacterium longum subspecies infantis) dominated the stool microbiota, with Proteobacteria and Bacteroidetes increasing by 15 weeks. Actinobacteria abundance was positively associated with T-cell responses to BCG, OPV, and TT; with the delayed-type hypersensitivity response; with immunoglobulin G responses; and with TI. B longum subspecies infantis correlated positively with TI and several vaccine responses. Bacterial diversity and abundance of Enterobacteriales, Pseudomonadales, and Clostridiales were associated with neutrophilia and lower vaccine responses.CONCLUSIONS: Bifidobacterium predominance may enhance thymic development and responses to both oral and parenteral vaccines early in infancy, whereas deviation from this pattern, resulting in greater bacterial diversity, may cause systemic inflammation (neutrophilia) and lower vaccine responses. Vaccine responsiveness may be improved by promoting intestinal bifidobacteria and minimizing dysbiosis early in infancy.

BACKGROUND: The intestinal microbiome in early infancy affects immunologic development and thus may affect vaccine memory, though few prospective studies have examined such associations. We examined the association of Bifidobacterium levels in early infancy with memory responses to early vaccination measured at 2 years of age. METHODS: In this prospective observational study, we examined the association of Bifidobacterium abundance in the stool of healthy infants at 6 to 15 weeks of age, near the time of vaccination, with T-cell and antibody responses measured at 6 weeks, 15 weeks, and 2 years of age. Infants were vaccinated with Bacillus Calmette-Guérin (BCG) (at birth), oral polio virus (at birth and at 6, 10, and 14 weeks), tetanus toxoid (TT) (at 6, 10, and 14 weeks), and hepatitis B virus (at 6, 10, and 14 weeks). Fecal Bifidobacterium was measured at 6, 11, and 15 weeks. Bifidobacterium species and subspecies were measured at 6 weeks. RESULTS: Mean Bifidobacterium abundance in early infancy was positively associated with the CD4 T-cell responses to BCG, TT, and hepatitis B virus at 15 weeks, with CD4 responses to BCG and TT at 2 years, and with plasma TT-specific immunoglobulin G and stool polio-specific immunoglobulin A at 2 years. Similar associations were seen for the predominant subspecies, Bifidobacterium longum subspecies infantis. CONCLUSIONS: Bifidobacterium abundance in early infancy may increase protective efficacy of vaccines by enhancing immunologic memory. This hypothesis could be tested in clinical trials of interventions to optimize Bifidobacterium abundance in appropriate populations.

Background: Low birth weight is generally an outcome of a fetal insult or nutritional insufficiency. Recent studies have shown that such exposure early in life may have long-term implications for later immunocompetence and susceptibility to infectious diseases. Objective: We aimed to investigate the effect of birth weight on immune function in preschool-age children. Design: A birth cohort cross-sectional study was conducted in children (n ҃ 132) aged 60.8 Ȁ 0.32 mo who were born in Matlab, a rural area of Bangladesh, and whose weight and length were measured within 72 h of birth. The outcome measures were thymopoiesis, T cell turnover, acute phase response, and percentage of lymphocytes. Results: Children born with low birth weight (2500 g; LBW group, n ҃ 66) had significantly higher concentrations of T cell receptor excision circles in peripheral blood mononuclear cells-a biomarker for thymopoiesis-and significantly higher serum bactericidal activity and C-reactive protein concentrations than did children born with normal birth weight (ͧ2500 g; NBW group, n ҃ 66) (P 0.05 for both). The LBW group children had significantly lower concentrations of interleukin 7 in plasma (P ҃ 0.02), shorter telomere length in peripheral blood mononuclear cells (P ҃ 0.02), and a lower percentage of CD3 T cells (P ҃ 0.06) than did the NBW group children. Conclusions: Greater peripheral T cell turnover (shorter telomeres and lower CD3 concentrations) due to immune activation (elevated C-reactive protein concentrations and bactericidal activity) may have resulted in a greater need for replenishment from the thymus (higher T cell receptor excision circles); these events may cause lower immune functional reserve in preschool-age children born with LBW. Thus, LBW has implications for immunocompetence and increased vulnerability to infectious diseases in later life.Am J Clin Nutr 2007;85:845-52.