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Microbial alterations cause increased intestinal permeability, and the penetration of bacterial fragment and toxins induces local and systemic inflammatory processes, affecting distant organs, including the brain. Therefore, the integrity of the intestinal epithelial barrier plays a central role in the microbiota\u2013gut\u2013brain axis. In this review, we discuss recent findings on zonulin, an important tight junction regulator of intestinal epithelial cells, which is assumed to play a key role in maintaining of the blood\u2013brain barrier function. In addition to focusing on the effect of microbiome on intestinal zonulin release, we also summarize potential pharmaceutical approaches to modulate zonulin-associated pathways with larazotide acetate and other zonulin receptor agonists or antagonists. The present review also addresses the emerging issues, including the use of misleading nomenclature or the unsolved questions about the exact protein sequence of zonulin.<\/jats:p>","DOI":"10.3390\/ijms24087548","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T03:25:11Z","timestamp":1681961111000},"page":"7548","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-8779","authenticated-orcid":false,"given":"Apor","family":"Veres-Sz\u00e9kely","sequence":"first","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary"},{"name":"ELKH-SE Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csenge","family":"Sz\u00e1sz","sequence":"additional","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domonkos","family":"Pap","sequence":"additional","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary"},{"name":"ELKH-SE Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00e1ta","family":"Szebeni","sequence":"additional","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary"},{"name":"ELKH-SE Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Bokrossy","sequence":"additional","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1d\u00e1m","family":"Vannay","sequence":"additional","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Semmelweis University, 1083 Budapest, Hungary"},{"name":"ELKH-SE Pediatrics and Nephrology Research Group, 1052 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota-gut-brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. 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