<i>Bifidobacterium infantis</i> associates with T cell immunity in human infants and is sufficient to enhance antigen-specific T cells in mice

Abstract

Bacille Calmette-Guerin (BCG) vaccine can elicit good T_H1 responses in neonates. We hypothesized that the pioneer gut microbiota affects vaccine T cell responses. Infants who are HIV exposed but uninfected (iHEU) display an altered immunity to vaccination. BCG-specific immune responses were analyzed at 7 weeks of age in iHEU, and responses were categorized as high or low. <i>Bifidobacterium longum</i> subsp. <i>infantis</i> was enriched in the stools of high responders, while <i>Bacteroides thetaiotaomicron</i> was enriched in low responders at time of BCG vaccination. Neonatal germ-free or SPF mice orally gavaged with live <i>B. infantis</i> exhibited significantly higher BCG-specific T cells compared with pups gavaged with <i>B. thetaiotaomicron. B. infantis</i> and <i>B. thetaiotaomicron</i> differentially affected stool metabolome and colonic transcriptome. Human colonic epithelial cells stimulated with <i>B. infantis</i> induced a unique gene expression profile versus <i>B. thetaiotaomicron</i>. We thus identified a causal role of <i>B. infantis</i> in early-life antigen-specific immunity.