Probiotic formula intervention in infants leads to colonization and competitive strain displacement independent of IgA binding

Early-life microbiota assembly is affected by environmental exposure, diet, and immunity. We performed shotgun metagenomics sequencing of fecal samples (N=401) from a controlled infant intervention trial to evaluate how pre- and probiotic exposure affects bacterial strain dynamics, maternal-to-offspring strain transmissibility, strain persistence, and host immune responses. Species- and strain-level analyses revealed that the early-life intervention with Bifidobacterium longum subsp. infantis (BL subsp. infantis), Bifidobacterium breve, and galacto-oligosaccharides (GOS) replaced main resident strains of these species unlike breast-feeding and exclusive infant formula. BL subsp. infantis low-diversity clusters were representative of several populations and were enriched for genes linked to recombination, mobilization, and antimicrobial activity. lnterestingly, Bifidobacterium bifidum but not Bifidobacterium longum or B. breve was heavily targeted by mucosal lgA, regardless of feeding type. These findings suggest that early-life pro- and prebiotic interventions promote colonization of specific dominant strains, potentially by outcompeting and displacing existing strains, independently of host immune responses.