Abstract
The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. Here we perform metagenomic analysis of earliest gut microbial community structures and functions. We identify differences in encoded functions between microbiomes of vaginally delivered (VD) and CSD neonates. Several functional pathways are over-represented in VD neonates, including lipopolysaccharide (LPS) biosynthesis. We link these enriched functions to individual-specific strains, which are transmitted from mothers to neonates in case of VD. The stimulation of primary human immune cells with LPS isolated from early stool samples of VD neonates results in higher levels of tumour necrosis factor (TNF-α) and interleukin 18 (IL-18). Accordingly, the observed levels of TNF-α and IL-18 in neonatal blood plasma are higher after VD. Taken together, our results support that CSD disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune-stimulatory potential during a critical window for neonatal immune system priming.
Highlights
The rate of caesarean section delivery (CSD) is increasing worldwide
Due to conflicting results, which principally imply a negligible impact of delivery mode on the colonizing neonatal microbiome in the gut[11], it remains unclear whether disruption of mother-to-infant transmission of microbiota through CSD occurs and whether it affects human physiology early on, with potentially persistent effects in later life
While previous studies have used analogous analytical approaches (16S rRNA gene amplicon sequencing and metagenomics) to resolve the early neonatal gut microbiome, these studies did not involve the systematic collection and appropriate preservation of paired mother–neonate samples[11], they did not track vertical strain transfer[11,18], they did not include provisions for the removal of artefactual sequences[3,5,6,11,18], they did not focus on the earliest time points after delivery[3,18], nor did they resolve differences in functional potential according to delivery mode[3,5,6,11,18]
Summary
The rate of caesarean section delivery (CSD) is increasing worldwide. It remains unclear whether disruption of mother-to-neonate transmission of microbiota through CSD occurs and whether it affects human physiology. As the first few days after birth represent a ‘critical window’ in neonatal health and development[12,13,14], there is growing concern that disruption of microbial transmission from mother to neonate is linked to conditions more frequently observed in CSD-born individuals, including allergies[15], chronic immune disorders[16] and metabolic disorders[17] To address these concerns, it is essential to determine if there are differences in the functional complement conferred by the earliest colonizing microbiota in relation to CSD, if any differences result from changes in the transmission of strains from mothers to neonates, and if these impact neonatal physiology. The removal of any artefactual sequences is essential to ensure unambiguous, highresolution overviews of the earliest microbial colonization of the neonatal gut
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