{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:55:21Z","timestamp":1792803321737,"version":"4.5.0"},"reference-count":295,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Carol Davila University of Medicine and Pharmacy","id":[{"id":"https:\/\/ror.org\/04fm87419","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This review explores the maternal gut microbiome\u2019s role in shaping neonatal neurodevelopmental outcomes following perinatal asphyxia (PA), a leading cause of infant mortality and disability with limited therapeutic options beyond hypothermia. We synthesized current evidence on microbiome-mediated neuroprotective mechanisms against hypoxic-ischemic brain injury. The maternal microbiome influences fetal development through bioactive metabolites (short-chain fatty acids, indole derivatives) that cross the placental barrier, bacterial antigen regulation, and infant microbiome colonization. These pathways activate multiple protective mechanisms: anti-inflammatory signaling via NF-\u03baB suppression and regulatory T cell expansion; antioxidant defenses through Nrf2 activation; neural repair via BDNF upregulation and neurogenesis; and oxytocin system modulation. Animal models demonstrate that maternal dysbiosis from high-fat diet or antibiotics exacerbates PA-induced brain damage, increasing inflammatory markers and hippocampal injury. Conversely, probiotic supplementation, dietary fiber, and specific interventions (omega-3, resveratrol) reduce neuroinflammation and oxidative injury. Human studies link maternal dysbiosis-associated conditions (obesity, gestational diabetes) with adverse pregnancy outcomes, though direct clinical evidence for PA severity remains limited. Understanding the maternal microbiome-fetal brain axis opens therapeutic avenues, including prenatal probiotics, dietary modifications, and targeted metabolite supplementation to prevent or mitigate PA-related neurological sequelae, potentially complementing existing neuroprotective strategies.<\/jats:p>","DOI":"10.3390\/antiox14091134","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T10:08:58Z","timestamp":1758276538000},"page":"1134","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Does the Maternal Gut Microbiome Influence the Outcome of Perinatal Asphyxia?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0946-0962","authenticated-orcid":false,"given":"Vlad-Petru","family":"Morozan","sequence":"first","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"},{"name":"Department of Plastic and Reconstructive Microsurgery, Central Military Emergency University Hospital \u2018Dr. Carol Davila\u2019, 010825 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara I.","family":"Ionescu","sequence":"additional","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"},{"name":"Department of Pediatrics II, Marie Curie Emergency Children\u2019s Hospital, 75534 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen M. D.","family":"Zahiu","sequence":"additional","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Catrina","sequence":"additional","affiliation":[{"name":"Cantacuzino National Military Medical Institute for Research and Development, 050096 Cernica, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea","family":"Racovi\u021b\u0103","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Elias University Hospital, 011461 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Teodora","family":"Chiril\u0103","sequence":"additional","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2397-7728","authenticated-orcid":false,"given":"Ioana-Alexandra","family":"Dogaru","sequence":"additional","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristian","family":"Ciotei","sequence":"additional","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6384-1822","authenticated-orcid":false,"given":"Gratiela Gradisteanu","family":"Pircalabioru","sequence":"additional","affiliation":[{"name":"Research Institute of the University of Bucharest, 050663 Bucharest, Romania"},{"name":"eBio-Hub Centre of Excellence in Bioengineering, National University of Science and Technology Politehnica Bucharest, 061344 Bucharest, Romania"},{"name":"Department of Botany and Microbiology, University of Bucharest, 060101 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4302-629X","authenticated-orcid":false,"given":"Ana-Maria","family":"Z\u0103grean","sequence":"additional","affiliation":[{"name":"Division of Physiology\u2014Neuroscience, Carol Davila University of Medicine and Pharmacy, 02001 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1016\/S0140-6736(16)31593-8","article-title":"Global, Regional, and National Causes of under-5 Mortality in 2000\u201315: An Updated Systematic Analysis with Implications for the Sustainable Development Goals","volume":"388","author":"Liu","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.earlhumdev.2010.05.010","article-title":"Epidemiology of Neonatal Encephalopathy and Hypoxic-Ischaemic Encephalopathy","volume":"86","author":"Kurinczuk","year":"2010","journal-title":"Early Hum. 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