Prenatal depression represents a common psychological illness that affects women during pregnancy. The gut--brain axis, which encompasses bidirectional communication between the gut and the brain, is postulated to contribute to the development of depression.

This study aims to understand the relationship between intestinal microbiota, inflammation, and depression during pregnancy using a bioinformatics approach.

A total of 220 differentially expressed genes (DEGs) associated with prenatal depression and intestinal inflammation and with a fold change > 1 and an adjusted p-value < 0.05 were selected from different databases and scientific publications. The genes were analysed using STRING software to construct a PPI network, SRplot was used for GO analysis and for the identification of biological functions, and finally MetaboAnalyst was used for the analysis and interpretation of metabolomics data in biological systems.

The results demonstrated the existence of an interaction protein--protein network comprising 205 genes, which led to the identification of 16 key genes involved in neuroinflammation and immune regulation processes. The key pathways identified included cytokine--cytokine receptor interaction, IL-17, and MAPK signalling. A relationship was predicted between DEG and metabolites such as cortisol, serotonin, and tryptophan in cases of prenatal depression and neuroinflammation. Gut dysbiosis during pregnancy can potentially increase intestinal permeability, which may subsequently trigger immune responses and brain neuroinflammation.

This study has identified pivotal genes that contribute to our understanding of the molecular mechanisms underlying the development of prenatal depression and may serve as potential targets for early detection, prevention, and treatment.