Genomic atlas of Bifidobacterium infantis and B. longum informs infant probiotic design

• Genome catalog of 4,098 B. infantis and B. longum shows distinct biogeography and ecology • B. infantis is depleted in Westernized populations but highly common in LMIC infants • Massively expanded B. infantis diversity and functions are absent from current probiotics • Geo-specific strain library informs diet- and population-tailored infant probiotic design Genome catalog of 4,098 B. infantis and B. longum shows distinct biogeography and ecology B. infantis is depleted in Westernized populations but highly common in LMIC infants Massively expanded B. infantis diversity and functions are absent from current probiotics Geo-specific strain library informs diet- and population-tailored infant probiotic design Bifidobacterium longum and B. infantis are pioneer colonizers of the neonatal gut and are widely used as probiotics to support infant growth, development, and disease resistance. However, commercial strains derived largely from high-income countries (HICs) may be suboptimal for infants in low- and middle-income countries (LMICs). We assembled a global genomic atlas of more than 4,000 genomes from 48 countries, increasing representation from LMICs by 12- to 17-fold. High-resolution phylogenomic and functional analyses support delineating B. longum and B. infantis as distinct species with divergent functions and epidemiological patterns. B. infantis dominates early-life microbiota in LMICs but is rarely detected in HICs. Natural B. infantis strains show extreme biogeographic stratification and predicted adaptations to local plant-glycan-rich diets and breast-milk-derived substrates, including urea and B vitamins. This genomic resource enables genome-guided selection of geographically matched strains to inform more effective probiotics and precision microbiome therapeutics for diverse infant populations.