Quantitative insights into effects of intrapartum antibiotics and birth mode on infant gut microbiota in relation to well-being during the first year of life

Background and aims Caesarean section (CS)-birth and maternally administered intrapartum antibiotics (IP) affect colonization of the neonate. We compared the effects of CS delivery and IP antibiotics on infant gut microbiota development and wellbeing over the first year. To understand the developing community dynamics, we focused on absolute bacterial abundance estimates over relative abundances. Methods We studied 144 healthy infants born between gestational weeks 37-42 vaginally without antibiotics (N=58), with IP penicillin (N=25) or cephalosporin (N=13), or by CS with IP cephalosporin (N=34) or other antibiotics (N=14). Gut microbiota composition and temporal development was analysed at 5-7 time points during the first year of life using 16S rRNA gene amplicon sequencing, complemented with qPCR to obtain absolute abundance estimates in 92 infants. 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. Results Based on absolute abundance estimates, depletion of Bacteroides spp. was specific to CS birth while decreased bifidobacteria and increased Bacilli were common to CS birth and exposure to IP antibiotics in vaginal delivery. Abundance of numerous taxa differed between the birth modes among cephalosporin-exposed infants. Penicillin had a milder impact on the infant gut microbiota than cephalosporin. The effects of both CS birth and IP antibiotics on infant gut microbiota associated with increased gastrointestinal symptoms during the first months. Conclusion CS birth and maternal IP antibiotics have both specific and overlapping effects on infant gut microbiota development. The resulting microbiota deviations were found to associate with gastrointestinal symptoms in infancy.