Akkermansia muciniphila supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses
Open accessAbstract
The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of Akkermansia muciniphila (A. muciniphila) in the mouse gut microbiota was significantly reduced after 7 days of SD. A. muciniphila pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. A. muciniphila pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that A. muciniphila pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. A. muciniphila supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.
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Sleep deprivation induces gut dysbiosis and intestinal barrier disruption, leading to microglial activation and cognitive decline.
“sleep deprivation (SD) induces gut dysbiosis and intestinal barrier disruption, leading to microglial activation and cognitive decline”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [648]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Li, N., Tan, S., Wang, Y., Deng, J., Wang, N., Zhu, S., Tian, W., Xu, J., & Wang, Q.
- Affiliations
- First Affiliated Hospital of Xi'an Jiaotong University (CN)
- Xi'an Honghui Hospital (CN)
- Xijing Hospital (CN)
- Department of Pharmacy, No. 95829 Military Hospital of PLA, Wuhan, Hubei, China
- Corresponding author
- Xu, Jing
- Wang, Qiang
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2023-09-06
- Volume
- 15
- Issue
- 2
- Pages
- 2252764-2252764
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC10484034
- OpenAlex
- W4386466415
- Cited by
- 117
- References
- 52
- Citations by year
- 2026: 41 · 2025: 49 · 2024: 27
- FWCI
- 10.43
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Gut Microbes (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81974540)
- Innovation Capability Support Program of Shaanxi (2021TD-58)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- Akkermansia muciniphila, sleep deprivation, cognitive impairment, gut microbiota, microbiome-gut-brain axis, synaptic loss, hippocampus, short-chain fatty acids, acetate, butyrate, microglial activation, lipopolysaccharide stimulation, fecal microbiota transplantation, antibiotic-induced dysbiosis, mild cognitive impairment
- MeSH terms
- Gastrointestinal Microbiome, Akkermansia, Animals, Sleep, Sleep Deprivation, Synapses, Microglia, Dietary Supplements, Mice, Cognitive Dysfunction, Dysbiosis
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