{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:45:29Z","timestamp":1792449929421,"version":"4.5.0"},"reference-count":192,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T00:00:00Z","timestamp":1744156800000},"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>Short-chain fatty acids (SCFAs), mainly produced by gut microbiota through the fermentation process of dietary fibers and proteins, are crucial to human health, with butyrate, a famous four-carbon SCFA, standing out for its inevitably regulatory impact on both gut and immune functions. Within this narrative review, the vital physiological functions of SCFAs were examined, with emphasis on butyrate\u2019s role as an energy source for colonocytes and its ability to enhance the gut barrier while exhibiting anti-inflammatory effects. Knowledge of butyrate synthesis, primarily generated by Firmicutes bacteria, can be influenced by diets with specifically high contents of resistant starches and fiber. Butyrate can inhibit histone deacetylase, modulate gene expression, influence immune functionality, and regulate tight junction integrity, supporting the idea of its role in gut barrier preservation. Butyrate possesses systemic anti-inflammatory properties, particularly, its capacity to reduce pro-inflammatory cytokines and maintain immune homeostasis, highlighting its therapeutic potential in managing dysbiosis and inflammatory diseases. Although butyrate absorption into circulation is typically minimal, its broader health implications are substantial, especially regarding obesity and type 2 diabetes through its influence on metabolic regulation and inflammation. Furthermore, this narrative review thoroughly examines butyrate\u2019s growing recognition as a modulator of neurological health via its interaction with the gut\u2013brain axis. Additionally, butyrate\u2019s neuroprotective effects are mediated through activation of specific G-protein-coupled receptors, such as FFAR3 and GPR109a, and inhibition of histone deacetylases (HDACs). Research indicates that butyrate can alleviate neurological disorders, including Alzheimer\u2019s, Parkinson\u2019s, autism spectrum disorder, and Huntington\u2019s disease, by reducing neuroinflammation, enhancing neurotransmitter modulation, and improving histone acetylation. This focus will help unlock its full therapeutic potential for metabolic and neurological health, rather than exclusively on its well-known benefits for gut health, as these are often interconnected.<\/jats:p>","DOI":"10.3390\/nu17081305","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T05:03:07Z","timestamp":1744174987000},"page":"1305","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Beyond the Gut: Unveiling Butyrate\u2019s Global Health Impact Through Gut Health and Dysbiosis-Related Conditions: A Narrative Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6141-862X","authenticated-orcid":false,"given":"Arda Erkan","family":"Kalkan","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics, \u00c7anakkale Onsekiz Mart University, \u00c7anakkale 17100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona N.","family":"BinMowyna","sequence":"additional","affiliation":[{"name":"College of Education, Shaqra University, Shaqra 11911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5286-2249","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Raposo","sequence":"additional","affiliation":[{"name":"CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lus\u00f3fona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3353-0457","authenticated-orcid":false,"given":"Md Faruque","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7243-791X","authenticated-orcid":false,"given":"Faiyaz","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, P.O. Box 6666, Buraydah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3565-6013","authenticated-orcid":false,"given":"Abdullah Y.","family":"Otayf","sequence":"additional","affiliation":[{"name":"Department of Clinical Nutrition, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2802-7873","authenticated-orcid":false,"given":"Conrado","family":"Carrascosa","sequence":"additional","affiliation":[{"name":"Department of Animal Pathology and Production, Bromatology and Food Technology, Faculty of Veterinary, Universidad de Las Palmas de Gran Canaria, Trasmonta\u00f1a s\/n, 35413 Arucas, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariana","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Research in Veterinary Medicine (I-MVET), Faculty of Veterinary Medicine, Lisbon University Centre, Lus\u00f3fona University, Campo Grande 376, 1749-024 Lisboa, Portugal"},{"name":"Veterinary and Animal Research Centre (CECAV), Faculty of Veterinary Medicine, Lisbon University Centre, Lus\u00f3fona University, Campo Grande 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sercan","family":"Karav","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, \u00c7anakkale Onsekiz Mart University, \u00c7anakkale 17100, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.3748\/wjg.v17.i12.1519","article-title":"Potential beneficial effects of butyrate in intestinal and extraintestinal diseases","volume":"17","author":"Canani","year":"2011","journal-title":"World J. 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