Birth interventions and infant gut microbiota. 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.

研究背景与目的：剖宫产（Caesarean section, CS）分娩与产妇分娩期使用的抗生素（intrapartum antibiotics, IP）会影响新生儿的菌群定植。本研究比较了剖宫产分娩与分娩期抗生素给药对婴儿出生后第一年肠道菌群发育及健康状况的影响。为阐明菌群群落的动态发育过程，本研究聚焦于细菌绝对丰度估算值而非相对丰度开展分析。
方法：本研究纳入144名孕周37~42周的健康足月婴儿，根据分娩方式与抗生素暴露情况分为5组：无抗生素暴露的阴道分娩组（N=58）、分娩期青霉素给药阴道分娩组（N=25）、分娩期头孢菌素给药阴道分娩组（N=13）、剖宫产分娩联合分娩期头孢菌素给药组（N=34）以及剖宫产分娩联合其他抗生素给药组（N=14）。采用16S rRNA基因扩增子测序技术，对婴儿出生后第一年的5~7个时间点的肠道菌群组成与时序发育特征进行分析；同时通过定量聚合酶链反应（quantitative PCR, qPCR）对其中92名婴儿的肠道菌群绝对丰度进行估算，以补充测序数据。此外，本研究开展中介分析，以明确与胃肠道功能及不适症状（啼哭、排便频率及胃肠道症状体征）相关的菌群分类群，以及与分娩干预措施相关的菌群分类群。
结果：基于绝对丰度的分析结果显示，拟杆菌属（Bacteroides spp.）丰度降低为剖宫产分娩所特有；而双歧杆菌属丰度降低、芽孢杆菌纲（Bacilli）丰度升高，为剖宫产分娩与阴道分娩时暴露于分娩期抗生素所共有的特征。在暴露于头孢菌素的婴儿中，不同分娩方式间的多种菌群分类群丰度存在显著差异。青霉素对婴儿肠道菌群的影响较头孢菌素更为温和。剖宫产分娩与分娩期抗生素给药二者对婴儿肠道菌群的影响，均与出生后前数月胃肠道症状发生率升高相关。
结论：剖宫产分娩与产妇分娩期抗生素给药，对婴儿肠道菌群发育均存在特异性与重叠性影响。上述肠道菌群结构偏离与婴儿期胃肠道症状存在显著关联。