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Their effectiveness in addressing conditions such as depression, anxiety, insomnia, stress, autism spectrum disorder (ASD), and eating disorders were examined through a comprehensive analysis of existing studies up to the first half of 2024, based on data from reliable electronic databases. We found that psychobiotics can significantly reduce symptoms of various psychiatric disorders by influencing neurotransmitter levels, regulating the hypothalamic-pituitary-adrenal (HPA) axis, and improving gut barrier function through short-chain fatty acids (SCFAs) and other metabolites. However, several limitations were identified, including inconsistent study methodologies, small sample sizes, and a lack of data on long-term safety. Addressing these limitations through rigorous research is essential for establishing standardized protocols and fully confirming the therapeutic potential of psychobiotics. In conclusion, psychobiotics show great promise as complementary treatments for mental health conditions, but continued research is necessary to refine their application and integrate them into clinical practice effectively.<\/jats:p>","DOI":"10.3390\/ijms26051972","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T03:40:12Z","timestamp":1740454812000},"page":"1972","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Can We Modulate Our Second Brain and Its Metabolites to Change Our Mood? A Systematic Review on Efficacy, Mechanisms, and Future Directions of \u201cPsychobiotics\u201d"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2223-4338","authenticated-orcid":false,"given":"Stefania","family":"Garzone","sequence":"first","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-7483","authenticated-orcid":false,"given":"Ioannis Alexandros","family":"Charitos","sequence":"additional","affiliation":[{"name":"Istituti Clinici Scientifici Maugeri IRCCS, Pneumology and Respiratory Rehabilitation Unit, \u201cInstitute\u201d of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8992-4622","authenticated-orcid":false,"given":"Manuela","family":"Mandorino","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5421-881X","authenticated-orcid":false,"given":"Maria Elena","family":"Maggiore","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-1743","authenticated-orcid":false,"given":"Loredana","family":"Capozzi","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy"},{"name":"Istituto Zooprofilattico Sperimentale della Puglia e della Basilicata, 71121 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6428-3383","authenticated-orcid":false,"given":"Bujar","family":"Cakani","sequence":"additional","affiliation":[{"name":"Department of Clinical Disciplines, \u201cAlexander Xhuvani\u201d University of Elbasan, 3001 Elbasan, Albania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-5873","authenticated-orcid":false,"given":"Gabriel C\u00e9sar","family":"Dias Lopes","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Mental Health, School of Science of Health, Logos University International (UNILOGOS), Miami, FL 33137, USA"},{"name":"Department of Neuroscience and Mental Health, School of Science of Health, European International University, 75018 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9801-603X","authenticated-orcid":false,"given":"Luisella","family":"Bocchio-Chiavetto","sequence":"additional","affiliation":[{"name":"IRCCS Centro San Giovanni di Dio Fatebenefratelli, 25125 Brescia, Italy"},{"name":"Department of Theoretical and Applied Sciences (DiSTA), eCampus University, 22060 Novedrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0806-4327","authenticated-orcid":false,"given":"Marica","family":"Colella","sequence":"additional","affiliation":[{"name":"Interdisciplinary Department of Medicine, Section of Microbiology and Virology, School of Medicine, University of Bari, 70124 Bari, Italy"},{"name":"Department of Theoretical and Applied Sciences (DiSTA), eCampus University, 22060 Novedrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Ballini, A., Charitos, I.A., Cantore, S., Topi, S., Bottalico, L., and Santacroce, L. 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