The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclearwhether disruption of mother-to-neonate transmission of microbiota through CSD occurs andwhether it affects human physiology. Here we perform metagenomic analysis of earliest gutmicrobial community structures and functions. We identify differences in encoded functionsbetween microbiomes of vaginally delivered (VD) and CSD neonates. Several functionalpathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis.We link these enriched functions to individual-specific strains, which are transmittedfrom mothers to neonates in case of VD. The stimulation of primary human immunecells with LPS isolated from early stool samples of VD neonates results in higher levels oftumour necrosis factor (TNF-α) and interleukin 18 (IL-18). Accordingly, the observed levelsof TNF-α and IL-18 in neonatal blood plasma are higher after VD. Taken together, our resultssupport that CSD disrupts mother-to-neonate transmission of specific microbial strains,linked functional repertoires and immune-stimulatory potential during a critical window forneonatal immune system priming.