Association and potential mechanisms between maternal amniotic fluid microbiota heterogeneity and fetal complex congenital heart disease

Background and aims Numerous studies have found that dysbiosis of the microbiota is associated with cardiovascular diseases in humans and shows certain links to congenital heart disease (CHD) in children. However, direct evidence regarding whether maternal gut microbiota is related to fetal heart development remains lacking. This study aims to collect amniotic fluid samples during cesarean sections from pregnant women, compare the differences in microbiota between fetuses with complex CHD and normal fetuses, and explore the role of maternal gut microbiota as an environmental pathogenic factor in complex CHD. Methods and results Amniotic fluid samples were collected from patients undergoing cesarean sections at a single center between November 2024 and October 2025. The study included 6 cases in the fetal complex congenital heart disease (CCHD) group and 9 cases in the fetal normal (NOR) group. Microbial 16S rRNA sequencing was performed on these samples. A total of 1,908,431 paired-end reads were obtained, which were assembled into 1,897,612 tags, corresponding to 4,057 ASVs/OTUs. No significant differences in microbial diversity were observed between the two groups. However, in the complex congenital heart disease (CCHD) group, the abundance of certain microbial taxa associated with diabetes, inflammatory bowel disease, and periodontal disease was significantly elevated. (p < 0.01). Conclusion No significant differences were observed in the microbial diversity of amniotic fluid between fetuses with complex congenital heart disease (CCHD) and normal fetuses. However, the abundance of specific microbial taxa was significantly elevated in the CCHD group. Further research is needed to elucidate the impact of these microbial changes on fetal cardiac development.