Early-life immune imprinting by a B. infantis-HMO synbiotic shapes infant immune signatures and protects against experimental respiratory disease.

Rashid, Ridwan B; Chung, Cheong Kwong; Namubiru, Patricia; Ahmed, Tufael; CLARA Study Group; Howard, Daniel R; Sebina, Ismail; Wilkins, Tyler et al. · Cell Rep Med · 2026

basic_science · Level V

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Abstract

Early microbial colonization influences immune development, with lower abundance of human milk oligosaccharide (HMO)-utilizing bifidobacteria linked to immune-related disorder risk. Here, we demonstrate that synbiotic supplementation with Bifidobacterium 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 reduces lower respiratory tract infection (LRI) severity and aberrant type-2 immune responses and confers lasting immune benefits into adulthood. These effects are associated with changes in the circulating metabolome, including increased 12(S)-hydroxyheptadecatrienoic acid (12-HHT), which correlates with improved infection outcomes and phenocopies synbiotic-mediated protection when administered orally. Together, these findings indicate that infant-type synbiotic supplementation during a critical early-life window can imprint immune function and promote disease tolerance.