{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:57:48Z","timestamp":1788328668503,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chongqing Municipal Health Commission and Chongqing Science and Technology Bureau","award":["2020ZY013802"],"award-info":[{"award-number":["2020ZY013802"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Tauroursodeoxycholic acid (TUDCA), a bile acid conjugate, has been suggested to improve cognition in models of Alzheimer\u2019s disease (AD), although its underlying mechanisms remain unclear. This study aimed to evaluate the effects of TUDCA and its potential pathways in APP\/PS1 mice. Behavioral tests, assessments of amyloid-\u03b2 (A\u03b2) deposition, neuroinflammation, peripheral inflammatory responses, intestinal barrier integrity, and gut microbiota composition were performed, along with pseudo-sterile mouse experiments and fecal microbiota transplantation (FMT). The expression of genes related to the TLR4\/NF-\u03baB\/NLRP3 pathway was also examined. TUDCA significantly ameliorated cognitive impairments, reduced A\u03b2 accumulation, and suppressed inflammatory responses in both the central nervous system and peripheral tissues. It improved intestinal barrier function and reshaped gut microbial composition by reducing pro-inflammatory taxa. FMT demonstrated that TUDCA-modulated microbiota contributed to improved learning and memory in AD mice, whereas antibiotic-induced pseudo-sterility indicated that TUDCA also exerted cognitive benefits independent of gut flora. Moreover, TUDCA inhibited the activation of the TLR4\/NF-\u03baB\/NLRP3 pathway. In conclusion, TUDCA alleviates AD-related cognitive deficits partly through modulation of the microbiota\u2013gut\u2013brain axis while also acting via microbiota-independent mechanisms, supporting its potential as a promising therapeutic strategy for AD.<\/jats:p>","DOI":"10.3390\/cimb48010087","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T14:35:38Z","timestamp":1768487738000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["TUDCA Ameliorates Cognitive Impairment in APP\/PS1 Mice by Modulating the Microbiota\u2013Gut\u2013Brain Axis"],"prefix":"10.3390","volume":"48","author":[{"given":"Minxia","family":"Zhan","sequence":"first","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunzhong","family":"Fu","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijin","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxian","family":"Song","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henghua","family":"Li","sequence":"additional","affiliation":[{"name":"Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liancai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochu","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400045, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1016\/S0140-6736(20)32205-4","article-title":"Alzheimer\u2019s disease","volume":"397","author":"Scheltens","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2023). 2023 Alzheimer\u2019s disease facts and figures. 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