Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis
Abstract Time‐restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via the gut‐brain axis remains elusive. In a clinical trial, we observed, for the first time, that a 4‐month TRF ameliorated cognitive impairments among Alzheimer's dise...
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Wiley
2025-04-01
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| Online Access: | https://doi.org/10.1002/imt2.70006 |
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| author | Yihang Zhao Mengzhen Jia Chen Ding Bingkun Bao Hangqi Li Jiabin Ma Weixuan Dong Rui Gao Xuhui Chen Jiao Chen Xiaoshuang Dai Yuanqiang Zou Jun Hu Lin Shi Xuebo Liu Zhigang Liu |
| author_facet | Yihang Zhao Mengzhen Jia Chen Ding Bingkun Bao Hangqi Li Jiabin Ma Weixuan Dong Rui Gao Xuhui Chen Jiao Chen Xiaoshuang Dai Yuanqiang Zou Jun Hu Lin Shi Xuebo Liu Zhigang Liu |
| author_sort | Yihang Zhao |
| collection | DOAJ |
| description | Abstract Time‐restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via the gut‐brain axis remains elusive. In a clinical trial, we observed, for the first time, that a 4‐month TRF ameliorated cognitive impairments among Alzheimer's disease (AD) patients. Experiments in 5xFAD mice corroborated the gut microbiota‐dependent effect of TRF on mitigating cognitive dysfunction, amyloid‐beta deposition, and neuroinflammation. Multi‐omics integration linked Bifidobacterium pseudolongum (B. pseudolongum) and propionic acid (PA) with key genes in AD pathogenesis. Oral supplementation of B. pseudolongum or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood‐brain barrier penetration, while knockdown of the free fatty acid receptor 3 (FFAR3) diminished TRF's cognitive benefits. Notably, we observed a positive correlation between fecal PA and improved cognitive function in an AD cohort, further indicating that TRF enhanced PA production. These findings highlight the microbiota‐metabolites‐brain axis as pivotal in TRF's cognitive benefits, proposing B. pseudolongum or PA as potential AD therapies. |
| format | Article |
| id | doaj-art-1b3b0d9bda4e4231bbcc93c6784dac9a |
| institution | OA Journals |
| issn | 2770-596X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | iMeta |
| spelling | doaj-art-1b3b0d9bda4e4231bbcc93c6784dac9a2025-08-20T02:11:49ZengWileyiMeta2770-596X2025-04-0142n/an/a10.1002/imt2.70006Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axisYihang Zhao0Mengzhen Jia1Chen Ding2Bingkun Bao3Hangqi Li4Jiabin Ma5Weixuan Dong6Rui Gao7Xuhui Chen8Jiao Chen9Xiaoshuang Dai10Yuanqiang Zou11Jun Hu12Lin Shi13Xuebo Liu14Zhigang Liu15College of Food Science and Engineering Northwest A&F University Yangling ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaThe First Affiliated Hospital of Xi'an Jiaotong University Xi'an ChinaThe First Affiliated Hospital of Xi'an Jiaotong University Xi'an ChinaPeking University Shenzhen Hospital Shenzhen ChinaPeking University Shenzhen Hospital Shenzhen ChinaXbiome Shenzhen ChinaBGI Research Shenzhen ChinaPeking University Shenzhen Hospital Shenzhen ChinaShaanxi Normal University Xi'an ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaCollege of Food Science and Engineering Northwest A&F University Yangling ChinaAbstract Time‐restricted feeding (TRF) holds promise for alleviating cognitive decline in aging, albeit the precise mechanism via the gut‐brain axis remains elusive. In a clinical trial, we observed, for the first time, that a 4‐month TRF ameliorated cognitive impairments among Alzheimer's disease (AD) patients. Experiments in 5xFAD mice corroborated the gut microbiota‐dependent effect of TRF on mitigating cognitive dysfunction, amyloid‐beta deposition, and neuroinflammation. Multi‐omics integration linked Bifidobacterium pseudolongum (B. pseudolongum) and propionic acid (PA) with key genes in AD pathogenesis. Oral supplementation of B. pseudolongum or PA mimicked TRF's protective effects. Positron emission tomography imaging confirmed PA's blood‐brain barrier penetration, while knockdown of the free fatty acid receptor 3 (FFAR3) diminished TRF's cognitive benefits. Notably, we observed a positive correlation between fecal PA and improved cognitive function in an AD cohort, further indicating that TRF enhanced PA production. These findings highlight the microbiota‐metabolites‐brain axis as pivotal in TRF's cognitive benefits, proposing B. pseudolongum or PA as potential AD therapies.https://doi.org/10.1002/imt2.70006Alzheimer's diseasegut microbiotapropionic acidtime‐restricted feeding |
| spellingShingle | Yihang Zhao Mengzhen Jia Chen Ding Bingkun Bao Hangqi Li Jiabin Ma Weixuan Dong Rui Gao Xuhui Chen Jiao Chen Xiaoshuang Dai Yuanqiang Zou Jun Hu Lin Shi Xuebo Liu Zhigang Liu Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis iMeta Alzheimer's disease gut microbiota propionic acid time‐restricted feeding |
| title | Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis |
| title_full | Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis |
| title_fullStr | Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis |
| title_full_unstemmed | Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis |
| title_short | Time‐restricted feeding mitigates Alzheimer's disease‐associated cognitive impairments via a B. pseudolongum‐propionic acid‐FFAR3 axis |
| title_sort | time restricted feeding mitigates alzheimer s disease associated cognitive impairments via a b pseudolongum propionic acid ffar3 axis |
| topic | Alzheimer's disease gut microbiota propionic acid time‐restricted feeding |
| url | https://doi.org/10.1002/imt2.70006 |
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