Imbalances in the gut microbiota and metabolome are associated with functional constipation in pregnancy

Functional constipation in pregnancy (FCP) is a common gastrointestinal disorder unique to pregnant women. The gut microbiota supports gastrointestinal function and maintains immune homeostasis, suggesting gut microbiota can become the target for FCP prevention and treatment. However, it remains unclear whether and how the gut microbiota and its correlated metabolites change for FCP. In this study, we aimed to explore the role of the gut microbiota in the pathogenesis of FCP and provide a reference for the selection of probiotics in further clinical trials. We comprehensively profiled the gut microbiota, Bifdobacterium and Bacteroides communities via high throughput sequencing, and faecal metabolome based on untarged metabolomics and targeted metabolomics of short-chain fatty acids (SCFAs) in 100 patients with FCP and 100 matched pregnant controls. We found that gut dysbiosis occurs in FCP patients, characterised by a reduced abundance of SCFAs-producing bacteria (e.g., Faecaliberium) and the enrichment of several opportunistic bacteria (e.g., Escherichia-Shigella), which were highly correlated with the clinical indicators of FCP. Furthermore, a reduced abundance of anti-inflammatory metabolites was seen, particularly arachidonic acid (AA) and butyric acid. We observed a complex co-occurrence between FCP-associated microorganisms and discriminative metabolites in an integrated network, with AA and Ruminococcaceae UCG-002 being identified as the main contributors. Collectively, imbalances in the gut microbiota and metabolome are associated with functional constipation in pregnancy. These findings provide a greater understanding of the pathogenesis and targets for probiotic interventions in FCP.