{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:23:26Z","timestamp":1787203406741,"version":"build-2736575974"},"reference-count":94,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Prenatal alcohol exposure (PAE) leads to fetal alcohol spectrum disorder (FASD), the most common preventable cause of neurodevelopmental impairment. The classical narrative attributes the clinical picture of FASD exclusively to direct ethanol-induced brain injury. In the present review, we argue that this perspective is incomplete and leads to diagnostic errors, most often to the misdiagnosis of ADHD in children who in fact have FASD. We propose that, alongside the direct neurotoxicity of ethanol, an important and clinically under-recognized complementary mechanism is gut\u2013brain axis dysfunction: alcohol damages the enteric nervous system and enteric glial cells, induces dysbiosis with deep deficits of butyrate and other short-chain fatty acids (SCFAs), damages the enterochromaffin cells responsible for 90% of peripheral serotonin production, and\u2014through translocation of lipopolysaccharide (LPS) and activation of the Toll-like receptor 4 (TLR4)\u2014sustains a neuroinflammatory brain signature. This cascade\u2014superimposed on direct ethanol neurotoxicity\u2014may account for the high rates of depression, anxiety, self-injurious behavior, and suicide attempts observed in individuals with FASD and for the limited efficacy of traditional interventions focused solely on the central nervous system. The 2024 Polish Institute of Mother and Child (Okulicz-Kozaryn et al.) study showed that 50.3% of pregnant women consumed alcohol, and 11% did so regularly, against only 7% who admitted so in questionnaires. The real clinical picture of children with FASD is further complicated by three factors to which we devote separate sections in this paper: prenatal co-exposure to nicotine, cannabinoids, and opioids; the loss of vertical microbiota transmission and breastfeeding in children transferred to foster care (where the prevalence of FASD is 18.8% and in children\u2019s homes in some regions reaches up to 80%); and the substantial over-representation of preterm and small-for-gestational-age (SGA) infants (in the Hasken et al. cohort, 18.4% of children with FASD were born preterm and 51.4% were born SGA). In the final section, we present a structured, staged protocol for nutritional and microbiological intervention grounded in a hierarchy of evidence: from interventions supported by randomized controlled trials (RCT-level; choline) through interventions supported by strong mechanistic rationale and RCTs in related populations (sodium butyrate, Lactobacillus rhamnosus GG, GOS\/FOS prebiotics\u2014galacto-oligosaccharides and fructo-oligosaccharides, and omega-3 fatty acids) to experimental interventions. The protocol also covers the window before 2 years of age: we argue that, given the over-representation of preterm and SGA infants among children with FASD, the analogy to preterm infants on parenteral nutrition and to post-institutional infants applies in substantial part to the same patients, which justifies extending the indications for choline and other nutritional interventions. The paper includes a compact table of dosing proposals for each age window (from pregnancy to school-age child) and provides clinicians with concrete answers: where to start, what to avoid, and what to monitor, with explicit signposting of regulatory limitations for individual substances in Poland and the European Union.<\/jats:p>","DOI":"10.3390\/jcm15166390","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T16:12:11Z","timestamp":1787069531000},"page":"6390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Gut\u2013Brain Axis in Fetal Alcohol Spectrum Disorder (FASD): Why the Gut Shapes Behavior, Depression, and Self-Injurious Behavior in Children with Prenatal Alcohol Exposure\u2014A Narrative Review with a Proposal for Staged Nutritional and Microbiological Intervention"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4305-8328","authenticated-orcid":false,"given":"Katarzyna","family":"Zych-Krekora","sequence":"first","affiliation":[{"name":"Department of Perinatology, Obstetrics and Gynecology, Polish Mother\u2019s Memorial Hospital Research Institute (Instytut Centrum Zdrowia Matki Polki, ICZMP), 93-338 \u0141\u00f3d\u017a, Poland"},{"name":"Faculty of Medicine, University of Social Sciences (Spo\u0142eczna Akademia Nauk, SAN), 90-113 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9325-7304","authenticated-orcid":false,"given":"Oskar","family":"Sylwestrzak","sequence":"additional","affiliation":[{"name":"Department of Perinatology, Obstetrics and Gynecology, Polish Mother\u2019s Memorial Hospital Research Institute (Instytut Centrum Zdrowia Matki Polki, ICZMP), 93-338 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Krekora","sequence":"additional","affiliation":[{"name":"Department of Perinatology, Obstetrics and Gynecology, Polish Mother\u2019s Memorial Hospital Research Institute (Instytut Centrum Zdrowia Matki Polki, ICZMP), 93-338 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1001\/jamapediatrics.2017.1919","article-title":"Global Prevalence of Fetal Alcohol Spectrum Disorder Among Children and Youth: A Systematic Review and Meta-analysis","volume":"171","author":"Lange","year":"2017","journal-title":"JAMA Pediatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e290","DOI":"10.1016\/S2214-109X(17)30021-9","article-title":"Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis","volume":"5","author":"Popova","year":"2017","journal-title":"Lancet Glob. 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