{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T14:52:44Z","timestamp":1784386364467,"version":"3.55.0"},"reference-count":52,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T00:00:00Z","timestamp":1642636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RC 2020-2021, Prog. N\u00b0 26 (DDG n. 2\/2020"],"award-info":[{"award-number":["RC 2020-2021, Prog. N\u00b0 26 (DDG n. 2\/2020"]}]},{"name":"University of Bari, Italy","award":["Fondi di Ateneo 2017-18"],"award-info":[{"award-number":["Fondi di Ateneo 2017-18"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Altered gut\u2013brain communication can contribute to intestinal dysfunctions in the intestinal bowel syndrome. The neuroprotective high-fat, adequate-protein, low-carbohydrate ketogenic diet (KD) modulates the levels of different neurotransmitters and neurotrophins. The aim was to evaluate the effects of KD on levels of 5-HT, the receptors 5-HT3B and 5-HT4, the 5-HT transporter SERT, the neurotrophin BDNF, and its receptor TrkB in the colon and brain of a rat model of irritable bowel syndrome (IBS). Samples from Wistar rats exposed to maternal deprivation as newborns and then fed with a standard diet (IBS-Std) or KD (IBS-KD) for ten weeks were analyzed. As controls, unexposed rats (Ctrl-Std and Ctrl-KD) were studied. IBS-Std rats had a disordered enteric serotoninergic signaling shown by increased mucosal 5-HT content and reduced SERT, 5-HT3B, and 5-HT4 levels compared to controls. In the brain, these animals showed up-regulation of the BDNF receptor TrkB as a counteracting response to the stress-induced reduction of the neurotrophin. KD showed a dual effect in improving the altered 5-HT and BDNF systems. It down-regulated the increased mucosal 5-HT without affecting transporter and receptor levels. KD improved brain BDNF levels and established negative feedback, leading to a compensatory downregulation of TrkB to maintain a physiological steady state.<\/jats:p>","DOI":"10.3390\/ijms23031098","type":"journal-article","created":{"date-parts":[[2022,1,20]],"date-time":"2022-01-20T22:40:20Z","timestamp":1642718420000},"page":"1098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["The Ketogenic Diet Improves Gut\u2013Brain Axis in a Rat Model of Irritable Bowel Syndrome: Impact on 5-HT and BDNF Systems"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8255-4776","authenticated-orcid":false,"given":"Antonella","family":"Orlando","sequence":"first","affiliation":[{"name":"Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology \u201cS. de Bellis\u201d, IRCCS Research Hospital, 70013 Castellana Grotte, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-2317","authenticated-orcid":false,"given":"Guglielmina","family":"Chimienti","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-2198","authenticated-orcid":false,"given":"Maria","family":"Notarnicola","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Biochemistry, National Institute of Gastroenterology \u201cS. de Bellis\u201d, IRCCS Research Hospital, 70013 Castellana Grotte, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0538-6072","authenticated-orcid":false,"given":"Francesco","family":"Russo","sequence":"additional","affiliation":[{"name":"Laboratory of Nutritional Pathophysiology, National Institute of Gastroenterology \u201cS. de Bellis\u201d, IRCCS Research Hospital, 70013 Castellana Grotte, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1136\/gutjnl-2015-311240","article-title":"The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: A Rome Foundation working team literature review","volume":"66","author":"Sperber","year":"2017","journal-title":"Gut"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cgh.2011.08.015","article-title":"Diagnosis, comorbidities, and management of irritable bowel syndrome in patients in a large health maintenance organization","volume":"10","author":"Ladabaum","year":"2012","journal-title":"Clin. 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