Meta-Analysis of DNA methylation and gut microbiome data in preterm birth reveals epigenetic and microbial biomarkers for early diagnosis and probiotic-based intervention

Background: Globally, preterm birth continues to be a major contributor to neonatal morbidity and mortality. Developing early diagnostics and focused interventions requires an understanding of the molecular and microbiome factors causing preterm birth and also the identification of biomarkers. Methods: We integrated gut microbiome and DNA methylation data to identify biomarkers of preterm birth. Analysis of GSE120458 revealed 1,609 differentially methylated regions involved in immune, hormonal, and neurodevelopmental pathways. Microbiome profiling identified five altered genera: Faecalibacterium prausnitzii, Streptococcus, Blautia faecis, Gemella, and Agathobacter. Taxon Set Enrichment Analysis revealed that these genera were found to be associated with systemic diseases like diabetes, obesity, and inflammatory bowel disease. Results: We identified 1,649 genes targeted by 33 microbial metabolites, with 17 overlapping methylated genes indicating microbiome–epigenome interactions. These genes were linked to neuroimmune and synaptic pathways. Conclusion: Hub genes may serve as biomarkers for early intervention. Overall, the results connect microbial metabolism with epigenetic regulation in preterm birth.