Impact of Perioperative Antibiotic Prophylaxis in Caesarean Section on the Maternal Gut Microbiome: A Systematic Review

Background/Objectives: Caesarean section (CS) accounts for over 20% of global births and routinely involves perioperative antibiotic prophylaxis (PAP) to reduce surgical site infections. While the impact of such prophylaxis on neonatal microbiome development is well described, effects on the maternal gut microbiome remain underexplored. This systematic review synthesizes current evidence on how antibiotic prophylaxis during CS affects maternal gut microbiome composition and diversity—an underrepresented, but clinically relevant aspect of maternal–fetal medicine. Methods: A systematic literature search was conducted in Medline (PubMed), the Cochrane Library, and the WHO International Clinical Trials Registry Platform (ICTRP) through November 2024. Inclusion criteria were defined according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies used molecular techniques to report maternal gut microbiome outcomes (alpha- and beta-diversity). The search concentrated on beta-lactam antibiotics. Reference lists were screened, but no additional grey literature was searched. Synthesis followed the Synthesis Without meta-analysis (SWiM) approach. No review protocol was registered. The review received no external funding. Results: Out of 1011 records, three studies (total 286 mothers) met the inclusion criteria. All reported maternal microbiome outcomes secondarily to infant-focused research. Only one study provided pre- and post-birth stool samples. Applied antibiotic regimens, sequencing methods, and reported microbiome metrics for alpha- and beta-diversity varied considerably, thus limiting comparability of results. Due to high heterogeneity, no formal risk of bias was assessed. While taxonomic diversity changes were inconsistent, significant shifts in functional diversity metrics were observed postpartum. Conclusions: Evidence on maternal microbiome disruption following perioperative antibiotic prophylaxis in CS is methodologically fragmented and limited by small sample sizes and inconsistent antibiotic protocols. Nonetheless, functional diversity appears sensitive to antibiotic exposure. To improve clinical understanding and safety, maternal-focused studies using standardized protocols are urgently needed. The maternal microbiome may play a key role in both recovery and shaping the newborn’s early microbial environment.