Early life microbial colonization is a critical determinant of immune system development, with reduced abundance of infant type, human milk oligosaccharide (HMO)–utilizing bifidobacteria associated with an increased risk of immune related disorders.
Early life microbial colonization is a critical determinant of immune system development, with reduced abundance of infant type, human milk oligosaccharide (HMO)–utilizing bifidobacteria associated with an increased risk of immune related disorders. Here, we demonstrate that synbiotic supplementation with Bifidobacterium infantis (B. longum subsp. infantis LMG 11588) and a blend of six structurally diverse HMOs plus Bifidobacterium lactis (CNCM I-3446) altered gut microbiome composition, changed systemic immune cell-networks and reduced persistence of a T helper 2 (Th2) bias in formula fed infants, following a pattern observed in breastfed infants. In preclinical models, synbiotic supplementation reduced lower respiratory infection (LRI) severity and aberrant type-2 immune responses and conferred lasting immune benefits into adulthood. These effects were associated with changes in the circulating metabolome, including increased levels of the lipid mediator 12(S)-hydroxyheptadecatrienoic acid (12-HHT), which correlated with improved infection outcomes, and when supplemented orally, phenocopied synbiotic-mediated protection against LRI. Together, these findings suggest that infant type synbiotic supplementation during a critical early life window can imprint immune function and promote disease tolerance for long-term health.
Early life microbial colonization is a critical determinant of immune system development, with reduced abundance of infant type, human milk oligosaccharide (HMO)–utilizing bifidobacteria associated with an increased risk of immune related disorders. Here, we demonstrate that synbiotic supplementation with Bifidobacterium infantis (B. longum subsp. infantis LMG 11588) and a blend of six structurally diverse HMOs plus Bifidobacterium lactis (CNCM I-3446) altered gut microbiome composition, changed systemic immune cell-networks and reduced persistence of a T helper 2 (Th2) bias in formula fed infants, following a pattern observed in breastfed infants. In preclinical models, synbiotic supplementation reduced lower respiratory infection (LRI) severity and aberrant type-2 immune responses and conferred lasting immune benefits into adulthood. These effects were associated with changes in the circulating metabolome, including increased levels of the lipid mediator 12(S)-hydroxyheptadecatrienoic acid (12-HHT), which correlated with improved infection outcomes, and when supplemented orally, phenocopied synbiotic-mediated protection against LRI. Together, these findings suggest that infant type synbiotic supplementation during a critical early life window can imprint immune function and promote disease tolerance for long-term health.
Brigham and Women's Hospital