{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:04:12Z","timestamp":1784610252140,"version":"3.55.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Preterm birth (PTB), defined as delivery before 37 weeks, is a major cause of neonatal morbidity and mortality worldwide. Evidence suggests that both epigenetic dysregulation and gut microbial imbalance contribute to the inflammatory and metabolic disturbances associated with PTB; however, few studies have examined these factors in conjunction to identify integrated predictive biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to identify epigenetic and microbial signatures associated with PTB by integrating maternal second-trimester genome-wide DNA methylation profiles with gut microbiome composition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A case\u2013control study was conducted with 120 pregnant women, grouped into two categories: preterm (\u226437 weeks, n = 60) and full-term (&amp;gt;37 weeks, n = 60). Maternal blood and fecal samples were collected simultaneously. DNA methylation was profiled using the Illumina MethylationEPIC array, and gut microbiota were characterized through 16S rRNA sequencing. Differentially methylated regions (DMRs) and differentially abundant taxa were identified using FDR &amp;lt; 0.05. Sparse canonical correlation analysis and network modeling were applied to integrate the datasets and identify linked epigenetic\u2013microbial features predictive of PTB.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Women with PTB showed distinct methylation changes in immune and inflammation-related genes, including IL6, CXCL10, TNFAIP3, and PPARGC1A. Gut microbiome analysis revealed significantly reduced \u03b1-diversity (Shannon index: 2.81 \u00b1 0.31\n                      <jats:italic>vs<\/jats:italic>\n                      . 3.42 \u00b1 0.36, p = 0.002), enrichment of pro-inflammatory taxa (Prevotella, Sutterella, Veillonella), and depletion of beneficial genera, including Lachnospiraceae, Faecalibacterium, and Bifidobacterium. Integrated analysis showed strong cross-domain associations (r = 0.68, p &amp;lt; 0.001), linking immune-gene hypomethylation with enrichment of inflammatory taxa. The combined biomarker panel achieved high predictive performance (AUC = 0.87; sensitivity = 82%; specificity = 84%), outperforming methylation-only and microbiome-only models. Functional enrichment highlighted convergence on NF-\u03baB signaling, cytokine interactions, and butyrate metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The study shows that coordinated epigenetic alterations and gut microbial dysbiosis contribute to PTB. These biomarkers are detectable during the second trimester (18\u201324 weeks), supporting their potential for mid-pregnancy risk stratification. The integrated methylation\u2013microbiome signature offers strong potential for early, non-invasive prediction and supports development of targeted maternal interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1743283","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:19:54Z","timestamp":1784607594000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identifying epigenetic and microbial biomarkers for preterm birth using DNA methylation and gut microbiome data"],"prefix":"10.3389","volume":"16","author":[{"given":"Ping","family":"Huang","sequence":"first","affiliation":[{"name":"The First College of Clinical Medical Science, China Three Gorges University","place":["Yichang, Hubei, China"]},{"name":"Department of Gastroenterology, Yichang Central People's Hospital","place":["Yichang, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimin","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Affiliated People\u2019s Hospital of Fujian University of Traditional Chinese Medicine","place":["Fuzhou, Fujian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41390-020-01236-1","article-title":"Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm","volume":"89","author":"Bangma","year":"2021","journal-title":"Pediatr. Res."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2024.100745","article-title":"Preterm birth: A neuroinflammatory origin for metabolic diseases","volume":"37","author":"Diao","year":"2024","journal-title":"Brain Behavior Immunity-Health"},{"key":"B3","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1186\/s13148-020-00942-1","article-title":"Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants","volume":"12","author":"Everson","year":"2020","journal-title":"Clin. Epigenet."},{"key":"B4","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00281-020-00807-y","article-title":"Pathogenesis of preterm birth: bidirectional inflammation in mother and fetus","volume":"42","author":"Green","year":"2020","journal-title":"Semin. Immunopathology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1128\/msystems.01252-23","article-title":"Multi-omics analysis reveals the associations between altered gut microbiota, metabolites, and cytokines during pregnancy","volume":"9","author":"Huang","year":"2024","journal-title":"Msystems"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13600","article-title":"Genetics, epigenetics, and transcriptomics of preterm birth","volume":"88","author":"Jain","year":"2022","journal-title":"Am. J. Reprod. Immunol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1007\/s12275-022-2180-2","article-title":"Early gut microbiota in very low and extremely low birth weight preterm infants with feeding intolerance: a prospective case-control study","volume":"60","author":"Liu","year":"2022","journal-title":"J. Microbiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1724","DOI":"10.21037\/atm-21-5539","article-title":"Integrated metagenomics and metabolomics analysis of third-trimester pregnant women with premature membrane rupture: a pilot study","volume":"9","author":"Liu","year":"2021","journal-title":"Ann. Trans. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s13148-020-00909-2","article-title":"Epigenetic age and pregnancy outcomes: GrimAge acceleration is associated with shorter gestational length and lower birthweight","volume":"12","author":"Ross","year":"2020","journal-title":"Clin. Epigenet."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.3390\/microorganisms11092199","article-title":"The impact of maternal gut microbiota during pregnancy on fetal gut\u2013brain axis development and life-long health outcomes","volume":"11","author":"Sajdel-Sulkowska","year":"2023","journal-title":"Microorganisms"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1769","DOI":"10.2217\/epi-2019-0346","article-title":"Altered DNA methylation in human placenta after (suspected) preterm labor","volume":"12","author":"Schoorlemmer","year":"2020","journal-title":"Epigenomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"113336","DOI":"10.1016\/j.celrep.2023.113336","article-title":"Impaired gut microbiota-mediated short-chain fatty acid production precedes morbidity and mortality in people with HIV","volume":"42","author":"Sereti","year":"2023","journal-title":"Cell Rep."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.823757","article-title":"Longitudinal reduction in diversity of maternal gut Microbiota during pregnancy is observed in multiple low-resource settings: Results from the Women First trial","volume":"13","author":"Tang","year":"2022","journal-title":"Front. Microbiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s13148-023-01473-1","article-title":"Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator","volume":"15","author":"Wang","year":"2023","journal-title":"Clin. Epigenet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2191","DOI":"10.1001\/jama.2013.281053","article-title":"World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects","volume":"310","year":"2013","journal-title":"Jama"},{"key":"B16","doi-asserted-by":"publisher","first-page":"81","DOI":"10.4103\/2096-2924.320887","article-title":"Analysis of the microbiome based on 16S rRNA gene signature in women with preterm versus term birth","volume":"5","author":"Yu","year":"2021","journal-title":"Reprod. Dev. Med."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1743283\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T04:19:55Z","timestamp":1784607595000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1743283\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":16,"alternative-id":["10.3389\/fcimb.2026.1743283"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1743283","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]},"article-number":"1743283"}}