Infant stool microbiota at the time of vaccination at 6 w of age is associated with vaccine responses measured at 2 y of age

Abstract

Abstract Background Gut microbiota in early infancy may shape a host’s vaccine response. We have previously reported that a high relative abundance (RA) of Bifidobacterium in early infancy is associated with vaccine responses measured near the time of stool collection (Huda MN et al., Pediatrics 2014 134:e362). In this study, we expanded the sample size and tested if the RA of Bifidobacterium measured at the time of vaccination (between birth and 15 w) is associated with T-cell and antibody (Ab) responses to those vaccines measured at 2 y of age. Methods This study included 306 healthy Bangladeshi infants (NCT01583972, NCT02027610). Stool microbiota was assayed at 6, 11 and 15 w and between 2 and 3 y of age. Vaccine-specific T-cell proliferation responses to BCG (Bacillus Calmette–Guérin), OPV (oral poliovirus), TT (tetanus toxoids), and HBV (hepatitis B virus) were measured at 15 w and 2 y of age. Plasma and stool Ab were measured at 2 y. Tuberculin skin test was performed at 15 w. Results Bifidobacterium RA at 6 w was positively associated with T-cell responses to BCG, OPV, HBV and TT measured at 15 w and 2 y, as predicted. Bifidobacterium was not associated with plasma Ab response. The abundance of Firmicutes and Proteobacteria were negatively associated with some vaccine responses. Microbiota at 2 y did not show consistent, significant associations with T-cell response or systemic Ab responses but Bifidobacterium was positively associated with polio-specific stool IgA levels. Conclusion Bifidobacterium RA at the time of vaccination is associated with systemic and mucosal vaccine-specific T-cell responses measured later in life, suggesting that interventions to enhance Bifidobacterium in early infancy may improve vaccine responses later in life.