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Psychobiotics, broadly understood as live microorganisms or microbe\u2010derived products that interact with the microbiota\u2013gut\u2013brain axis, have been suggested to exert neuroactive effects through neural, immune, endocrine and metabolic routes. This narrative review synthesizes recent preclinical, mechanistic and early clinical observations. Experimental studies show that selected strains can modulate cytokine signalling, influence stress\u2010responsive systems such as the hypothalamic\u2013pituitary\u2013adrenal axis, and support synaptic plasticity via factors such as brain\u2010derived neurotrophic factor. A limited number of human trials using well\u2010characterized\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    and\n                    <jats:italic>Bifidobacterium<\/jats:italic>\n                    strains have reported improvements in affective and stress\u2010related outcomes, but these effects are generally small to moderate, more apparent in adjunctive than stand\u2010alone use, and dependent on strain, dose, population and intervention length (typically 4\u201312\u00a0weeks). Evidence on neurodevelopmental conditions (e.g., autism spectrum disorder, attention\u2010deficit\/hyperactivity disorder) remains preliminary, based on small and heterogeneous samples. Across studies, key constraints include methodological heterogeneity, incomplete strain\u2010level reporting, and gaps in mechanistic resolution that make it difficult to link microbial shifts to psychiatric benefit. Emerging microbiome\u2010 and metabolomics\u2010informed approaches may help identify likely responders and improve translational precision, but they are not yet ready for routine clinical application. Overall, psychobiotics should currently be viewed as a promising adjunct within integrative mental health care, warranting larger, standardized trials with clearly defined strains, doses and mechanistic endpoints.\n                  <\/jats:p>","DOI":"10.1113\/ep093301","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:40:01Z","timestamp":1773013201000},"page":"2449-2463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Psychobiotics and the microbiota\u2013gut\u2013brain axis: Emerging paradigms in mental health modulation"],"prefix":"10.1113","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6476-5998","authenticated-orcid":false,"given":"Amir Arsalan","family":"Ghahari","sequence":"first","affiliation":[{"name":"Neurosciences Research Center Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1347-9149","authenticated-orcid":false,"given":"Mehrdad","family":"Nourizadeh","sequence":"additional","affiliation":[{"name":"Neurosciences Research Center Tabriz University of Medical Sciences  Tabriz Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5274-8178","authenticated-orcid":false,"given":"Mehrdad","family":"SalekShahabi","sequence":"additional","affiliation":[{"name":"Department of Medicine, TaMS.C. 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