{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:05:50Z","timestamp":1790856350472,"version":"4.1.0"},"reference-count":14,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T00:00:00Z","timestamp":1506038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 \u00b5mol\/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer\u2019s disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study.<\/jats:p>","DOI":"10.3390\/nu9101053","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T11:03:15Z","timestamp":1506078195000},"page":"1053","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":160,"title":["The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5394-1259","authenticated-orcid":false,"given":"Daniele","family":"Del Rio","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Zimetti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Caffarra","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina e Chirurgia, Unit\u00e0 di Neuroscienze, Universit\u00e0 degli Studi di Parma, via Gramsci 14, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Tassotti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Bernini","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Furio","family":"Brighenti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Zini","sequence":"additional","affiliation":[{"name":"Dipartimento di Neuroscienze, Nuovo Ospedale Civile \u201cS.Agostino-Estense\u201d, Azienda Ospedaliera Universitaria, via Giardini 1355, 41100 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2701-6021","authenticated-orcid":false,"given":"Ilaria","family":"Zanotti","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze degli Alimenti e del Farmaco, Universit\u00e0 degli Studi di Parma, Parco Area delle Scienze 27\/A, 43124 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1056\/NEJMra1600266","article-title":"The human intestinal microbiome in health and disease","volume":"375","author":"Lynch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.tem.2016.10.005","article-title":"Trimethylamine-N-oxide: Friend, foe, or simply caught in the cross-fire?","volume":"28","author":"Cho","year":"2017","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1016\/j.jacc.2016.03.546","article-title":"Plasma trimethylamine N-oxide, a gut microbe-generated phosphatidylcholine metabolite, is associated with atherosclerotic burden","volume":"67","author":"Senthong","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1373\/clinchem.2016.264853","article-title":"Trimethylamine N-oxide and risk stratification after acute myocardial infarction","volume":"63","author":"Suzuki","year":"2017","journal-title":"Clin. Chem."},{"key":"ref_5","first-page":"1","article-title":"Gut microbiota-dependent trimethylamine N-oxide in acute coronary syndromes: A prognostic marker for incident cardiovascular events beyond traditional risk factors","volume":"38","author":"Li","year":"2017","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"778","DOI":"10.3945\/ajcn.114.087692","article-title":"Effect of egg ingestion on trimethylamine-N-oxide production in humans: A randomized, controlled, dose-response study","volume":"100","author":"Miller","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1016\/S1474-4422(14)70090-0","article-title":"Advancing research diagnostic criteria for Alzheimer\u2019s disease: The IWG-2 criteria","volume":"13","author":"Dubois","year":"2014","journal-title":"Lancet Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1016\/j.amjcard.2016.07.071","article-title":"Coronary plaque characterization assessed by optical coherence tomography and plasma trimethylamine-N-oxide levels in patients with coronary artery disease","volume":"118","author":"Fu","year":"2016","journal-title":"Am. J. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1161\/JAHA.116.004237","article-title":"Trimethylamine N-oxide and mortality risk in patients with peripheral artery disease","volume":"5","author":"Senthong","year":"2016","journal-title":"J. Am. Heart Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1055\/s-0035-1569330","article-title":"Diabetes is associated with higher trimethylamine N-oxide plasma levels","volume":"124","author":"Dambrova","year":"2016","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7442","DOI":"10.1158\/0008-5472.CAN-14-1835","article-title":"Plasma choline metabolites and colorectal cancer risk in the women\u2019s health initiative observational study","volume":"74","author":"Bae","year":"2014","journal-title":"Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1089\/jmf.2014.7000","article-title":"The gut microbiome and the brain","volume":"17","author":"Galland","year":"2014","journal-title":"J. Med. Food"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42296","DOI":"10.1038\/srep42296","article-title":"Functional coupling of human microphysiology systems: Intestine, liver, kidney proximal tubule, blood-brain barrier and skeletal muscle","volume":"7","author":"Vernetti","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev.pharmtox.46.120604.141043","article-title":"Human flavin-containing monooxygenases","volume":"46","author":"Cashman","year":"2006","journal-title":"Annu. Rev. Pharmacol. Toxicol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/10\/1053\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:45:38Z","timestamp":1760208338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/10\/1053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,22]]},"references-count":14,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["nu9101053"],"URL":"https:\/\/doi.org\/10.3390\/nu9101053","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,22]]}}}