{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:17:47Z","timestamp":1787671067659,"version":"build-2736575974"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"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. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Gestational diabetes mellitus (GDM) affects up to 27.6% of pregnancies in certain regions and is associated with a two- to threefold increased risk of neonatal infections. Although maternal gut microbiota undergoes significant remodeling during pregnancy, the specific mechanisms governing GDM-induced microbial reprogramming in offspring and its implications for susceptibility to infections remain unclear. This study aimed to investigate the impact of GDM on the composition of neonatal gut microbiota, metabolomic profiles, and susceptibility to infections using a translational approach.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We recruited pregnant women with and without GDM at the JinHua Municipal Central Hospital in China. Meconium and blood samples were collected from newborns within 24\u202fh of birth. The composition of the gut microbiota was analyzed using 16S rDNA amplicon sequencing, and short-chain fatty acids (SCFAs) were quantified using gas chromatography\u2013mass spectrometry. Serum inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP), lipopolysaccharides (LPS), and procalcitonin (PCT), were measured by enzyme-linked immunosorbent assay. To establish causality, fecal microbiota transplantation (FMT) was conducted in antibiotic-treated mice using pooled samples from healthy and GDM-exposed neonates, followed by assessment of inflammatory markers and intestinal barrier integrity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>GDM significantly reduced the diversity of neonatal gut microbiota and altered its composition, characterized by a depletion of beneficial taxa (<jats:italic>Bifidobacterium<\/jats:italic>, <jats:italic>Blautia<\/jats:italic>, <jats:italic>Faecalibacterium<\/jats:italic>) and an enrichment of potential pathogens (<jats:italic>Stenotrophomonas<\/jats:italic>, <jats:italic>Chryseobacterium<\/jats:italic>). These alterations were accompanied by significant reductions in fecal SCFAs, particularly acetate (49.30%), butyrate (41.00%), and propionate (17.83%). GDM-exposed neonates exhibited elevated serum inflammatory markers, including IL-6, CRP, LPS, and PCT, which correlated negatively with beneficial bacteria and positively with opportunistic pathogens. FMT experiments demonstrated that mice receiving GDM-associated microbiota developed increased systemic inflammation and compromised intestinal barrier function, as evidenced by the downregulation of tight junction proteins (<jats:italic>ZO-1<\/jats:italic>, occludin, claudin-1, mucin1). These findings suggest that GDM-induced alterations in neonatal gut microbiota composition and metabolite production may compromise intestinal barrier function and increase susceptibility to infections, highlighting the potential for microbiome-targeted interventions to mitigate infection risk in GDM-exposed neonates.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1600325","type":"journal-article","created":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T19:32:42Z","timestamp":1750707162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Gestational diabetes mellitus alters neonatal gut microbiota and increases infection susceptibility"],"prefix":"10.3389","volume":"16","author":[{"given":"Yifei","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunjie","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianbao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenghui","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanfang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1586\/eri.11.24","article-title":"Stenotrophomonas maltophilia: emerging disease patterns and challenges for treatment","volume":"9","author":"Abbott","year":"2011","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"100869","DOI":"10.1016\/j.nmni.2021.100869","article-title":"Chryseobacterium gleum bacteraemia: first reported cases from Qatar","volume":"41","author":"Ali","year":"2021","journal-title":"New Microbes New Infect."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"112","DOI":"10.3390\/microorganisms13010112","article-title":"Evaluation of Faecal microbiota following probiotics in infants of mothers with gestational diabetes mellitus trial: protocol for double-blind placebo-controlled randomized trial","volume":"13","author":"Athalye-Jape","year":"2025","journal-title":"Microorganisms"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1016\/j.scitotenv.2018.08.356","article-title":"Associations between maternal plasma measurements of inflammatory markers and urinary levels of phenols and parabens during pregnancy: a repeated measures study","volume":"650","author":"Aung","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12061070","article-title":"Decoding the gut microbiota-gestational diabetes link: insights from the last seven years","volume":"12","author":"Balleza-Alejandri","year":"2024","journal-title":"Microorganisms"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3390\/nu16234131","article-title":"The interactions between diet and gut microbiota in preventing gestational diabetes mellitus: a narrative review","volume":"16","author":"Beldie","year":"2024","journal-title":"Nutrients"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"5184","DOI":"10.1038\/s41467-018-07359-8","article-title":"Therapeutic faecal microbiota transplantation controls intestinal inflammation through IL10 secretion by immune cells","volume":"9","author":"Burrello","year":"2018","journal-title":"Nat. Commun."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"23129","DOI":"10.1038\/srep23129","article-title":"Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid","volume":"6","author":"Collado","year":"2016","journal-title":"Sci. Rep."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1038\/s41467-019-12563-1","article-title":"Spatiotemporal dynamics of multidrug resistant bacteria on intensive care unit surfaces","volume":"10","author":"D\u2019Souza","year":"2019","journal-title":"Nat. Commun."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"931574","DOI":"10.1155\/2015\/931574","article-title":"Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis","volume":"2015","author":"Da Maranduba","year":"2015","journal-title":"J Immunol Res"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"119622","DOI":"10.1016\/j.lfs.2021.119622","article-title":"Restoration of dysbiotic human gut microbiome for homeostasis","volume":"278","author":"Dixit","year":"2021","journal-title":"Life Sci."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.freeradbiomed.2012.10.554","article-title":"Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota","volume":"55","author":"Espey","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"bvz039","DOI":"10.1210\/jendso\/bvz039","article-title":"Intestinal barrier dysfunction, LPS translocation, and disease development","volume":"4","author":"Ghosh","year":"2020","journal-title":"J Endocr Soc"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"2393270","DOI":"10.1080\/19490976.2024.2393270","article-title":"The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease","volume":"16","author":"Hays","year":"2024","journal-title":"Gut Microbes"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1093\/rheumatology\/keh058","article-title":"Tissue production of pro-inflammatory cytokines (IL-1beta, TNFalpha and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis","volume":"43","author":"Hern\u00e1ndez-Rodr\u00edguez","year":"2004","journal-title":"Rheumatology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"53","DOI":"10.2174\/1874091X01004010053","article-title":"The impact of the level of the intestinal short chain fatty acids in inflammatory bowel disease patients versus healthy subjects","volume":"4","author":"Huda-Faujan","year":"2010","journal-title":"Open Biochem J"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s42523-024-00346-z","article-title":"Dietary \u03b2-mannanase reduced post-weaning diarrhea of pigs by positively modulating gut microbiota and attenuating systemic immune responses","volume":"6","author":"Jang","year":"2024","journal-title":"Anim Microbiome"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3390\/ijms24032471","article-title":"Necrotizing enterocolitis: the role of hypoxia, gut microbiome, and microbial metabolites","volume":"24","author":"Kaplina","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1016\/j.cell.2012.07.008","article-title":"Host remodeling of the gut microbiome and metabolic changes during pregnancy","volume":"150","author":"Koren","year":"2012","journal-title":"Cell"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1016\/j.cell.2024.01.029","article-title":"High fat intake sustains sorbitol intolerance after antibiotic-mediated Clostridia depletion from the gut microbiota","volume":"187","author":"Lee","year":"2024","journal-title":"Cell"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"2256749","DOI":"10.1080\/19490976.2023.2256749","article-title":"Alterations of milk oligosaccharides in mothers with gestational diabetes mellitus impede colonization of beneficial bacteria and development of ROR\u03b3t+ Treg cell-mediated immune tolerance in neonates","volume":"15","author":"Li","year":"2023","journal-title":"Gut Microbes"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/s41387-024-00346-7","article-title":"Gestational diabetes exacerbates intrauterine microbial exposure induced intestinal microbiota change in offspring contributing to increased immune response","volume":"14","author":"Liu","year":"2024","journal-title":"Nutr. Diabetes"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/ame2.12464","article-title":"Role of short-chain fatty acids in host physiology","volume":"7","author":"Liu","year":"2024","journal-title":"Animal Model Exp. Med."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s40168-024-02024-3","article-title":"No microorganism was detected in amniotic fluid of healthy pregnancies from the second trimester to the delivery","volume":"13","author":"Liu","year":"2025","journal-title":"Microbiome"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1017\/S2040174420000768","article-title":"Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice","volume":"11","author":"Liu","year":"2020","journal-title":"J. Dev. Orig. Health Dis."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s40168-023-01698-5","article-title":"Clec7a drives gut fungus-mediated host lipid deposition","volume":"11","author":"Ma","year":"2023","journal-title":"Microbiome"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1093\/femsre\/fuad039","article-title":"Faecalibacterium: a bacterial genus with promising human health applications","volume":"47","author":"Mart\u00edn","year":"2023","journal-title":"FEMS Microbiol. Rev."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.20517\/mrr.2023.10","article-title":"Microbial interactions and the homeostasis of the gut microbiome: the role of Bifidobacterium","volume":"2","author":"Martin","year":"2023","journal-title":"Microbiome Res. 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Med."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1186\/s12967-023-04230-3","article-title":"Maternal microbiota and gestational diabetes: impact on infant health","volume":"21","author":"Singh","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1186\/s12884-022-04630-1","article-title":"Influences of gestational diabetes mellitus on the oral microbiota in offspring from birth to 1 month old","volume":"22","author":"Song","year":"2022","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"2315","DOI":"10.1210\/clinem\/dgad107","article-title":"Association of Gestational Diabetes with the dynamic changes of gut microbiota in offspring from 1 to 6 months of age","volume":"108","author":"Song","year":"2023","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"3555","DOI":"10.1038\/s41467-018-05901-2","article-title":"Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis","volume":"9","author":"Sun","year":"2018","journal-title":"Nat. Commun."},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens11030300","article-title":"Pathogenesis of the Pseudomonas aeruginosa biofilm: a review","volume":"11","author":"Tuon","year":"2022","journal-title":"Pathogens"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s12866-024-03255-y","article-title":"Interactions between host and gut microbiota in gestational diabetes mellitus and their impacts on offspring","volume":"24","author":"Wang","year":"2024","journal-title":"BMC Microbiol."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"109050","DOI":"10.1016\/j.diabres.2021.109050","article-title":"IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by International Association of Diabetes in pregnancy study group's criteria","volume":"183","author":"Wang","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1007\/s40618-021-01595-4","article-title":"16S rRNA gene amplicon sequencing of gut microbiota in gestational diabetes mellitus and their correlation with disease risk factors","volume":"45","author":"Wei","year":"2022","journal-title":"J. Endocrinol. 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