Maternal Gut Microbiota in Gestational Diabetes Mellitus and Fetal Macrosomia: Is There an Association?

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with altered maternal gut microbiota and increased risk of large-for-gestational age (LGA) births. The contribution of gut microbiota to fetal overgrowth in GDM, independent of glycemic control, remains unclear. Methods: In this pilot longitudinal study, the gut microbiota of 18 women with GDM was followed from the second (2T) to the third trimester (3T). Maternal fecal samples were analyzed by 16S rRNA gene sequencing, and associations between microbial profiles and infant birth weight were examined. In addition, these associations were adjusted for pre-pregnancy body mass index (BMI) and gestational weight gain (GWG). Results: Maternal gut microbiota of LGA infants exhibited consistently lower microbial diversity, a reduced Bacillota/Bacteroidota ratio, and enrichment of pro-inflammatory taxa including Prevotella, Sutterella, and Bilophila. Short-chain fatty acids (SCFAs)-producing genera such as Acinetobacter, Odoribacter, Faecalibacterium, and Lachnoclostridium were depleted. Although Bilophila was identified as a third-trimester biomarker with LEfSE approach, its association with LGA disappeared after adjusting for BMI and GWG. Conversely, Nitrospirota, Polaromonas, Acinetobacter, and Aeromonas correlated negatively with LGA even after BMI and GWG adjustment. Conclusions: These findings suggest that specific maternal microbiota signatures, together with pre-pregnancy adiposity, influence fetal overgrowth in GDM and may serve as early biomarkers or targets for preventive interventions.