Birth mode and maternal intrapartum (IP) antibiotics affect infants' gut microbiota development, but their relative contribution to absolute bacterial abundances and infant health has not been studied. We compared the effects of Cesarean section (CS) delivery and IP antibiotics on infant gut microbiota development and well-being over the first year. We focused on 92 healthy infants born between gestational weeks 37-42 vaginally without antibiotics (N = 26), with IP penicillin (N = 13) or cephalosporin (N = 7) or by CS with IP cephalosporin (N = 33) or other antibiotics (N = 13). Composition and temporal development analysis of the gut microbiota concentrated on 5 time points during the first year of life using 16S rRNA gene amplicon sequencing, integrated with qPCR to obtain absolute abundance estimates. A mediation analysis was carried out to identify taxa linked to gastrointestinal function and discomfort (crying, defecation frequency, and signs of gastrointestinal symptoms), and birth interventions. Based on absolute abundance estimates, the depletion of Bacteroides spp. was found specifically in CS birth, while decreased bifidobacteria and increased Bacilli were common in CS birth and exposure to IP antibiotics in vaginal delivery. The abundances of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. CS birth and maternal IP antibiotics had both specific and overlapping effects on infants' gut microbiota development. The resulting deviations in the gut microbiota are associated with increased defecation rate, flatulence, perceived stomach pain, and intensity of crying in infancy.
Keywords: 16S rRNA gene amplicon sequencing; Early-life microbiota; antibiotics; birth route; cesarean section; quantitative microbiota profiling.