257-LB: Long-Term Effects of Birth Mode on Gut Microbiome Colonization

Background: Caesarean section (CS) disrupts mother-to-neonate transmission of specific microbial strains, linked functional repertoires and immune system priming. We investigated whether the differences in microbial populations and functional potentials persist at 1 year of age.

Methodology: We performed high-resolution, quantitative metagenomic analyses of the gut microbiomes of 8 infants born by vaginal delivery (VD) (n=3) or by CS (n=5) at 1 year. Metagenomic sequencing reads were used to generate functional repertoire profiles based on the homology of the assembled genes/contigs with the KEGG database. Simultaneously, LPS from the infant stool samples was used to stimulate primary immune cells (dendritic cells) obtained from healthy human donors. An enzyme-linked immunosorbent assay for TNFα was used to determine concomitant levels of cytokines. Differential mOTU (metagenomic operational taxonomic unit) and KEGG pathway analyses were performed using the DESeq2 R package.

Results: Seven mOTUs including Anaerotruncus colihominis, [Ruminococcus obeum], and Subdoligranulum variabile demonstrated between 10- to 30- fold enrichment in the VD samples compared to the CS group (p < 0.05). Although ordination analyses did not indicate significant differences between the groups, the functional repertoire analysis found several KEGG pathways differentially enriched when comparing VD and CS samples. The CS samples exhibited enrichments in CD226 antigen, cell adhesion and vancomycin resistance pathways, while the VD group had an increased abundance of carbon metabolism and epithelial cell invasion pathways. Previously increased TNFα levels observed in VD samples right after birth compared to the CS group, were not observed at 1 year.

Conclusion: After 1-year, persistent differences in gut mOTUs were observed between CS and VD born infants. Whether the CD226 pathway upregulation relates to human auto-immune disease, requires further analysis and validation.