Structural variation analysis suggests strain-level maternal-infant microbial transmission in early life

Structural variations (SVs)-large, functionally consequential genomic alterations-serve as high-resolution markers for strain-level differentiation in the human microbiome, yet their relevance to vertical transmission of the maternal microbiota and early-life colonization remains unclear.

Using metagenomic data from a 98-pair longitudinal mother-infant cohort and a 25-pair multi-niche cohort, we profiled microbial taxa, functions, and SVs, characterized variable SVs (vSVs), deletion SVs (dSVs), and transmitted SVs (tSVs), and evaluated the potential influence of delivery mode, feeding regimen, and maternal ecological niches.

We identified 5,578 SVs across 51 reference strains, with infants showing increasing SV diversity during the first year of life, and observed significantly greater SV similarity within mother-infant pairs than unrelated pairs. Abundance-based analysis identified 90 microbial species shared between mothers and infants. However, when incorporating SV-based tracking, only 14 strains showed patterns consistent with sustained maternal contribution across time points. Furthermore, exploratory subgroup analyses suggested that both delivery mode and feeding regimen may influence the vertical transmission patterns of maternal microbial strains and transmitted SVs. Functionally, tSVs were enriched in pathways linked to carbohydrate, amino acid, and lipid metabolism, as well as transport and environmental adaptation modules such as T4SS. Multi-niche analysis further suggested that the maternal gut showed the strongest inferred signal of SV-supported strain sharing with both the infant gut and oral microbiota.

Together, these findings suggest that microbial SVs can serve as complementary markers for investigating maternal contribution and vertical transmission-related strain-level patterns in early-life microbiome development, providing new insights into microbial inheritance and early-life health trajectories.