{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:09:02Z","timestamp":1787062142302,"version":"build-2736575974"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>The microbiota\u2013gut\u2013brain axis (MGBA) is a complex bidirectional communication network integrating neural, endocrine, immune, and metabolic pathways linking intestinal microbiota to central nervous system function. Increasing evidence indicates that microbiota-derived signals are critical regulators of neurodevelopment and may contribute to vulnerability to neurodegenerative disorders across the lifespan. In this narrative review, we synthesize experimental and clinical evidence to define the key biological mechanisms underlying microbiota\u2013brain interactions. Converging data indicate that immune activation, barrier dysfunction, and microbial metabolites, particularly short-chain fatty acids and tryptophan-derived compounds, represent central mediators linking gut dysbiosis to neuroinflammatory and neurodegenerative processes. Early-life microbial perturbations, driven by factors such as antibiotic exposure, diet, and psychosocial stress, appear to induce long-term immunometabolic programming that may increase susceptibility to neurological disorders later in life. Clinical studies consistently associate dysbiosis with neurodevelopmental conditions and major neurodegenerative diseases, including Alzheimer\u2019s disease and Parkinson\u2019s disease; however, causal relationships remain incompletely defined due to heterogeneity and the predominance of observational data. Overall, the available evidence supports a lifespan model in which microbiota-driven immune and metabolic dysregulation contributes to both early neurodevelopmental trajectories and late-life neurodegeneration. While microbiome-based biomarkers and therapeutic strategies show promise, their clinical translation requires validation in longitudinal and interventional studies.<\/jats:p>","DOI":"10.3390\/jcm15083065","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T10:11:04Z","timestamp":1776420664000},"page":"3065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Microbiota\u2013Gut\u2013Brain Axis Across the Lifespan: From Neurodevelopment to Neurodegeneration"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2557-9559","authenticated-orcid":false,"given":"Salvatore Michele","family":"Carnazzo","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilios","family":"Fanos","sequence":"additional","affiliation":[{"name":"Neonatal Intensive Care Unit, AOU Cagliari, Department of Surgical Sciences, University of Cagliari, 09124 Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-Altering Microorganisms: The Impact of the Gut Microbiota on Brain and Behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat. 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