iMeta
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2025
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IF 33.2
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 (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. Graphical A 4-month of time-restricted feeding (TRF) intervention alleviated cognitive impairments in Alzheimer's disease (AD) patients, while a 3-month TRF regimen improved spatial memory, reduced amyloid-beta accumulation, and promoted microglial aggregation around plaques in AD mice. Antibiotic-induced gut microbiota depletion partly abolished TRF's benefits. Through creatively integrating gut microbiota, metabolites, and hippocampal genes, Bifidobacterium pseudolongum ( B. pseudolongum ) and propionic acid (PA) were identified as key contributors to TRF's cognitive effects, with supplementation of either mimicking TRF's protective benefits. Positron emission tomography imaging revealed that PA directly crossed the blood-brain barrier, and PA supplementation restored disrupted metabolism in AD mice. Knockdown of its receptor free fatty acid receptor 3 (FFAR3) diminished TRF's protective effects. A case-control study showed a negative association between PA and cognitive status, while the TRF clinical intervention linked fecal PA to cognitive status. These findings suggest PA as a potential biomarker and underscore precise TRF-based nutritional interventions as a promising strategy for managing neurodegenerative diseases. Highlights Time-restricted feeding (TRF) improved cognitive function in Alzheimer's disease (AD) patients, with notable enhancement in executive function. Multi-omics integrated analysis in AD mice identified Bifidobacterium pseudolongum ( B. pseudolongum ) and propionic acid (PA) as key mediators of TRF's cognitive benefits. The potential molecular mechanism by which TRF alleviates cognitive impairment induced by AD involves the B. pseudolongum –PA-free fatty acid receptor 3 (FFAR3) pathway. Case-control study and TRF clinical intervention demonstrated PA as a potential biomarker for AD.
研究领域:
神经科学
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微生物学
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营养学
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分子生物学
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临床试验
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产品关联
DOI
PubMed
高影响因子
Foods
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2025
·Vol. 14
·期 1
·101
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IF 5.1
Run Yu,Haimeng Zhang,Rui Chen,Yangzhuo Lin,Jingxuan Xu,Ziyang Fang,Yuehang Ru,Chenhan Fan,Guoqing Wu
Alzheimer’s disease (AD) is marked by impaired cognitive functions, particularly in learning and memory, owing to complex and diverse mechanisms. Methionine restriction (MR) has been found to exert a mitigating effect on brain oxidative stress to improve AD. However, the bidirectional crosstalk between the gut and brain through which MR enhances learning and memory in AD, as well as the effects of fecal microbiota transplantation (FMT) from MR mice on AD mice, remains underexplored. In this study, APP/PS1 double transgenic AD mice were used and an FMT experiment was conducted. 16S rRNA gene sequencing, targeted metabolomics, and microbial metabolite short-chain fatty acids (SCFAs) of feces samples were analyzed. The results showed that MR reversed the reduction in SCFAs induced by AD, and further activated the free fatty acid receptors, FFAR2 and FFAR3, as well as the transport protein MCT1, thereby signaling to the brain to mitigate inflammation and enhance the learning and memory capabilities. Furthermore, the FMT experiment from methionine-restricted diet mouse donors showed that mice receiving FMT ameliorated Alzheimer’s learning and memory ability through SCFAs. This study offers novel non-pharmaceutical intervention strategies for AD prevention.
研究领域:
神经科学
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微生物学
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肠脑轴
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代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Zihao He,Siyuan Deng,Zhijing Wu,Zheng Cui,Hao Mei,Jinglin Wang,Kaiping Wang,Yu Zhang
Ethnopharmacological relevance Dysfunction of the intestinal barrier was an important trigger for alcoholic liver damage and alcohol had brought about intestinal damage before causing liver damage. The root of Angelica sinensis (Oliv.) Diels, crucial traditional medicinal material, was widely utilized for its blood-invigorating, intestinal-lubricating and gynecological benefits. Angelica sinensis polysaccharide (ASP) was an essential natural active ingredient of Angelica sinensis and exhibited considerable potential for gastrointestinal protection. Nevertheless, the systematic research of ASP on the gastrointestinal tract remained insufficient. Aim of this study To systematically explore the protective effect and underlying mechanisms of ASP against alcohol-induced gastrointestinal injury, including the stomach, ileum and colon. Materials and methods The AFLD mice model was established via the intragastric administration of alcohol twice a day for one week. The protective effect of ASP on the representative segments of the gastrointestinal tract (stomach, ileum and colon) was subsequently studied after confirming its hepatoprotective activity. The impact of ASP on gastrointestinal alcohol metabolism was examined to explain its antioxidant and antiapoptotic activities. Furthermore, the effect of ASP on short-chain fatty acids (SCFA) in the colon and colonic contents was investigated to further enhance the understanding of the underlying mechanisms. Results ASP could reduce oxidative stress and apoptosis in the gastrointestinal tract via regulating CYP2E1-mediated alcohol metabolism. Additionally, ASP could significantly increase the levels of FFAR2, FFAR3 and HCAR2 in colon, thereby promoting the utilization of SCFA. Conclusion ASP was proven for the first time to improve gastrointestinal damage caused by alcohol, indicating its enormous potential as a candidate medicine for the treatment of alcohol related gastrointestinal injury.
研究领域:
药理学
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胃肠病学
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肝病学
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营养保健品
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民族药理学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）