Gut microbiota mediates intermittent-fasting alleviation of diabetes-induced cognitive impairment
Open accessAbstract
Cognitive decline is one of the complications of type 2 diabetes (T2D). Intermittent fasting (IF) is a promising dietary intervention for alleviating T2D symptoms, but its protective effect on diabetes-driven cognitive dysfunction remains elusive. Here, we find that a 28-day IF regimen for diabetic mice improves behavioral impairment via a microbiota-metabolites-brain axis: IF enhances mitochondrial biogenesis and energy metabolism gene expression in hippocampus, re-structures the gut microbiota, and improves microbial metabolites that are related to cognitive function. Moreover, strong connections are observed between IF affected genes, microbiota and metabolites, as assessed by integrative modelling. Removing gut microbiota with antibiotics partly abolishes the neuroprotective effects of IF. Administration of 3-indolepropionic acid, serotonin, short chain fatty acids or tauroursodeoxycholic acid shows a similar effect to IF in terms of improving cognitive function. Together, our study purports the microbiota-metabolites-brain axis as a mechanism that can enable therapeutic strategies against metabolism-implicated cognitive pathophysiologies.
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Administration of microbial metabolites that were differentially increased after intermittent fasting resulted in improved cognitive function in animals, partially supporting a causal role for microbial metabolites in improving cognition.
“Recently, the administration of microbial metabolites that were found to be differentially increased after intermittent fasting resulted in improved cognitive function, partially supporting a causal role for microbial metabolites in improving cognition in animals (320).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [320]
In a recent study, alterations in microbial composition and metabolites that were associated with behavioral, neurochemical, and brain structural changes were observed after intermittent fasting in a diabetic mouse model.
“For example, in a recent study, alterations in microbial composition and metabolites that were associated with behavioral, neurochemical, and brain structural changes were observed after intermittent fasting in a diabetic mouse model (320).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [320]
The beneficial effect of intermittent fasting on cognitive impairment in a diabetic mouse model was partially abrogated after administration of an antibiotic cocktail.
“Likewise, the beneficial effect of intermittent fasting on cognitive impairment in a diabetic mouse model was partially abrogated after administration of an antibiotic cocktail (320).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [320]
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- Authors
- Liu, Z., Dai, X., Zhang, H., Shi, R., Hui, Y., Jin, X., Zhang, W., Wang, L., Wang, Q., Wang, D., Wang, J., Tan, X., Ren, B., Liu, X., Zhao, T., Wang, J., Pan, J., Yuan, T., Chu, C., Lan, L., Yin, F., Cadenas, E., Shi, L., Zhao, S., & Liu, X.
- Affiliations
- Northwest A&F University (CN)
- BGI Group (China) (CN)
- University of Arizona (US)
- University of Southern California (US)
- Chalmers University of Technology (SE)
- Corresponding author
- Liu, Zhigang
- Liu, Xiaoning
- Shi, Lin
- Zhao, Shancen
- Liu, Xuebo
- ORCID
- Venue
- Nature Communications
- Published
- 2020-02-18
- Volume
- 11
- Issue
- 1
- Pages
- 855-855
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7029019
- OpenAlex
- W3008031857
- Cited by
- 549
- References
- 65
- Citations by year
- 2026: 58 · 2025: 94 · 2024: 113 · 2023: 90 · 2022: 105 · 2021: 61 · 2020: 28
- FWCI
- 23.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by)
- Chalmers Research (Chalmers University of Technology) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81803231, 81871118)
- China Postdoctoral Science Foundation (2016M602867, 2018T111104)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- intermittent fasting, type 2 diabetes, gut microbiota, mitochondrial biogenesis, microbial metabolites, 3-indolepropionic acid, serotonin, short-chain fatty acids, tauroursodeoxycholic acid, cognitive decline
- MeSH terms
- Gastrointestinal Microbiome, Animals, Brain, Cognition, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Energy Metabolism, Fasting, Fatty Acids, Volatile, Gene Expression Regulation, Hippocampus, Indoles, Insulin Resistance, Male, Propionates, RNA, Ribosomal, 16S, Serotonin, Synapses, Taurochenodeoxycholic Acid, Computational Biology, Mice, Metabolome, Cognitive Dysfunction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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