{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T20:16:13Z","timestamp":1760472973238,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T00:00:00Z","timestamp":1612051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Trimethylaminuria (TMAU) is a rare metabolic syndrome characterized by the accumulation and the excretion of trimethylamine (TMA), a volatile diet compound produced by gut microbiota. Gut microbiota alterations are mainly involved in the secondary TMAU, whose patients show also different psychiatric conditions. We hypothesized that the biological activity of several molecules acting as intermediate in TMA metabolic reaction might be at the basis of TMAU psychiatric comorbidities. Methods: To corroborate this hypothesis, we performed the analysis of microbiota of both psychiatric suffering secondary TMAU patients and TMAU \u201cmentally ill\u201d controls, comparing the alteration of metabolites produced by their gut bacteria possibly involved in neurotransmission and, in the same time, belonging to biochemical pathways leading to TMA accumulation. Results: Microbiota analyses showed that Clostridiaceae, Lachnospiraceae and Coriobacteriaceae alterations represented the bacterial families with highest variations. This results in an excessive release of serotonin and an hyperactivation of the vagus nerve that might determine the widest spectrum of psychiatric disorders shown by affected patients. These metabolites, as short chain fatty acids, lactate and neurotransmitter precursors, are also related to TMA accumulation. Conclusions: Knowledge of microbiota-gut-brain axis may become a potential new strategy for improving metabolic diseases and to treat linked psychiatric disorders.<\/jats:p>","DOI":"10.3390\/jpm11020087","type":"journal-article","created":{"date-parts":[[2021,1,31]],"date-time":"2021-01-31T04:53:00Z","timestamp":1612068780000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gut-Brain Axis Cross-Talk and Limbic Disorders as Biological Basis of Secondary TMAU"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5292-426X","authenticated-orcid":false,"given":"Luigi","family":"Donato","sequence":"first","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy"},{"name":"Department of Biomolecular Strategies, Genetics and Avant-Garde Therapies, I.E.ME.S.T., 90139 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Alibrandi","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy"},{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4824-1693","authenticated-orcid":false,"given":"Concetta","family":"Scimone","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy"},{"name":"Department of Biomolecular Strategies, Genetics and Avant-Garde Therapies, I.E.ME.S.T., 90139 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Castagnetti","sequence":"additional","affiliation":[{"name":"Wellmicro Start Up, Innovative Spin-Off Alma Mater Studiorum Universit\u00e0 di Bologna, 40129 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Rao","sequence":"additional","affiliation":[{"name":"Central Health Superintendence, Prevention and Research Division, INAIL, 00144 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonina","family":"Sidoti","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6510-3121","authenticated-orcid":false,"given":"Rosalia","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1710","DOI":"10.1016\/j.drudis.2020.06.026","article-title":"Treatments of trimethylaminuria: Where we are and where we might be heading","volume":"25","author":"Schmidt","year":"2020","journal-title":"Drug Discov. 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