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Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation

Molecular Psychiatry volume 26, pages 6277–6292 (2021)Cite this article

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Abstract

Sleep deprivation (SD) is increasingly common in modern society, which can lead to the dysregulation of inflammatory responses and cognitive impairment, but the mechanisms remain unclear. Emerging evidence suggests that gut microbiota plays a critical role in the pathogenesis and development of inflammatory and psychiatric diseases, possibly via gut microbiota–brain interactions and neuroinflammation. The present study investigated the impact of SD on gut microbiota composition and explored whether alterations of the gut microbiota play a causal role in chronic inflammatory states and cognitive impairment that are induced by SD. We found that SD-induced gut dysbiosis, inflammatory responses, and cognitive impairment in humans. Moreover, the absence of the gut microbiota suppressed inflammatory response and cognitive impairment induced by SD in germ-free (GF) mice. Transplantation of the “SD microbiota” into GF mice activated the Toll-like receptor 4/nuclear factor-κB signaling pathway and impaired cognitive function in the recipient mice. Mice that harbored “SD microbiota” also exhibited increases in neuroinflammation and microglial activity in the hippocampus and medial prefrontal cortex. These findings indicate that gut dysbiosis contributes to both peripheral and central inflammatory processes and cognitive deficits that are induced by SD, which may open avenues for potential interventions that can relieve the detrimental consequences of sleep loss.

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Fig. 1: Sleep deprivation (SD) induced systemic inflammation and gut microbiome and metabolic dysbiosis.
Fig. 2: Absence of the gut microbiota suppressed the sleep deprivation (SD) induced inflammatory response and cognitive impairment in mice.
Fig. 3: Colonization of GF mice with the SD-associated microbiome amplified the detrimental effects of SD.
Fig. 4: Alterations of the gut microbiome and short-chain fatty acids (SCFAs) in mice that were colonized with fecal microbiota after SD.
Fig. 5: Colonization of germ-free (GF) mice with SD-associated microbiomes enhanced neuroinflammation in the medial prefrontal cortex and hippocampus.
Fig. 6: The gut microbiota modulates the inflammatory response and cognitive impairment that are associated with sleep deprivation.

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (no. 81901347, 32071058, 81821092, 31800897, 81770434) and National Key Research and Development Program of China (no. 2019YFC0118604).

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  1. These authors contributed equally: Zhong Wang, Wen-Hao Chen

Authors and Affiliations

  1. Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Chinese Academy of Medical Sciences Research Unit (No.2018RU006), Peking University, Beijing, China

    Zhong Wang, Wen-Hao Chen, Zhe Wang, Xi-Mei Zhu, Kai Yuan, Le Shi, Wei Yan & Lin Lu

  2. National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence, Peking University, Beijing, China

    Su-Xia Li, Wei-Li Zhu, Yan-Ping Bao, Shi-Qiu Meng, Yan-Xue Xue, Jie Shi & Ying Han

  3. Department of Laboratory Animal Science, College of Basic Medical Sciences, Third Military Medical University, Chongqing, China

    Zhong-Ming He

  4. Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, China

    Yan-Bin Ji

  5. Mental Health Center of Anhui Province, Hefei, China

    Wen Xie

  6. Precision Medicine Institute, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Hong Wei

  7. Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China

    Lin Lu

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Wang, Z., Chen, WH., Li, SX. et al. Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation. Mol Psychiatry 26, 6277–6292 (2021). https://doi.org/10.1038/s41380-021-01113-1

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