Discovery of Novel Probiotic Species to Improve Infant Health.

UNLABELLED: Selecting an appropriate infant formula can be challenging for parents given the wide range of available options, which may lead to suboptimal choices or frequent switching. Our recent studies in mice demonstrated that the maternal microbiota-particularly Limosilactobacillus reuteri present in breast milk-plays a critical role in shaping neonatal immunity by promoting the production of immunoglobulin A (IgA), a key antibody for defense against enteric pathogens. To extend these findings to humans, we analyzed fecal samples from healthy breastfed infants using shotgun metagenomic sequencing combined with whole-bacterial-cell ELISA to assess associations between specific taxa and pathogen-reactive IgA. We found that members of the Oscillibacter species (including Oscillibacter sp. KLE1728, KLE1745, PC13, PEA192, and O. valericigenes) and Morganella (e.g., M. morganii, Morganella sp. EGD-HP17, and Morganella sp. HMSC11D09) were strongly correlated with IgA responses against Salmonella and Shigella. In contrast, IgA reactive to enterohemorrhagic Escherichia coli (EHEC) was associated with other genera, including Staphylococcus. Notably, Lactobacillus species (L. bombi, L. kefiri, L. equi, and L. rhamnosus) were consistently linked to elevated IgA responses against Salmonella, Shigella, and EHEC. Moreover, levels of anti-Salmonella and anti-Shigella IgA were positively correlated with the use of infant formula containing prebiotic fibers or human milk oligosaccharides (5-HMO). Collectively, these findings highlight novel commensal taxa with potential as probiotic candidates to guide the development of next-generation infant formulas aimed at enhancing mucosal immunity and supporting infant health.

IMPORTANCE: Early-life nutrition shapes immune maturation, yet the microbial factors driving mucosal antibody responses remain poorly defined. Through integrated metagenomic and IgA profiling, this study identifies commensal taxa, particularly Lactobacillus, Oscillibacter, and Morganella, associated with pathogen-specific IgA in infants. These taxa may enhance mucosal defense against enteric pathogens, revealing key microbial contributors to early immune development. The findings provide a foundation for designing next-generation infant formulas that leverage targeted probiotics or prebiotics to promote protective IgA responses and gut health.