{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:17:05Z","timestamp":1789607825581,"version":"build-2803163510"},"reference-count":282,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:p>In recent years, an increasing number of researchers have become interested in the bidirectional communication between the gut microbiota and the central nervous system. This communication occurs through the microbiota-gut-brain axis. As people age, the composition of the gut microbiota undergoes considerable changes, which are now known to play an important role in the development of many neurodegenerative diseases. This review aims to investigate the complex bidirectional signaling pathways between the gut and the brain. It summarizes the latest research findings on how the gut microbiota and its metabolites play critical roles in regulating inflammation, maintaining gut health, and influencing the development of neurodegenerative diseases such as Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral sclerosis. The review also analyzes the current clinical applications of gut microbiota-based treatments for neurological disorders, including fecal microbiota transplantation, probiotics, and prebiotics. Many studies show that the gut microbiota affects the brain in several ways. For example, it can produce substances such as short-chain fatty acids and activate inflammatory pathways. Studies involving animals and laboratory models have demonstrated that adjusting the gut microbiota can help improve behavior and reduce neurological problems. Recent metagenomic and metabolomics studies have shown that the microbiota plays a crucial role in maintaining the organism\u2019s health. Microorganisms primarily colonize the gut and are involved in host nutrient metabolism, maintaining the structural integrity of the intestine, preserving the intestinal mucosal barrier, and modulating the immune system. The gut microbiota communicates with the brain through a bidirectional microbiota-gut-brain axis. The composition of the gut flora changes considerably with age, and ecological dysregulation has been recognized as one of the twelve most recent hallmarks of aging. Recent studies have linked these changes to a variety of age-related neurological disorders, including Alzheimer\u2019s disease, amyotrophic lateral sclerosis, Parkinson\u2019s disease, multiple sclerosis, and Huntington\u2019s disease. Specifically, the gut microbiota influences the brain through the production of key metabolites such as short-chain fatty acids and the activation of inflammatory and other relevant signaling pathways. In preclinical studies, targeted modulation of the gut microbiota, through methods such as fecal microbiota transplantation, probiotics, and prebiotics, has demonstrated potential in improving host behavioral outcomes. Therefore, gut microbiota-based treatments offer new hope for the treatment of nervous system diseases. However, due to the complexity of the gut microbiota and the potential adverse reactions associated with these therapies, researchers need to carefully assess their safety and efficacy before widespread clinical application.<\/jats:p>","DOI":"10.4103\/nrr.nrr-d-25-00434","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T06:00:59Z","timestamp":1756965659000},"page":"3411-3425","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":12,"title":["Bidirectional communication between the gut microbiota and the central nervous system"],"prefix":"10.4103","volume":"21","author":[{"given":"Yingxian","family":"Liu","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuoxian","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1361-3094","authenticated-orcid":false,"given":"Hang","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The Second Hospital of Jilin University, Changchun, Jilin Province, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2320-7613","authenticated-orcid":false,"given":"Zhenjiang","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, Jilin Province, 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