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Intestinal dysbiosis mediates cognitive impairment via the intestine and brain NLRP3 inflammasome activation in chronic sleep deprivation
Abstract
Growing evidence suggests the involvement of the microbiota-gut-brain axis in cognitive impairment induced by sleep deprivation (SD), however how the microbiota-gut-brain axis work remains elusive. Here, we discovered that chronic SD induced intestinal dysbiosis, activated NLRP3 inflammasome in the colon and brain, destructed intestinal/blood-brain barrier, and impaired cognitive function in mice. Transplantation of "SD microbiota" could almost mimic the pathological and behavioral changes caused by chronic SD. Furthermore, all the behavioral and pathological abnormalities were practically reversed in chronic sleep-deprived NLRP3-/- mice. Regional knockdown NLRP3 expression in the gut and hippocampus, respectively. We observed that down-regulation of NLRP3 in the hippocampus inhibited neuroinflammation, and ameliorated synaptic dysfunction and cognitive impairment induced by chronic SD. More intriguingly, the down-regulation of NLRP3 in the gut protected the intestinal barrier, attenuated the levels of peripheral inflammatory factors, down-regulated the expression of NLRP3 in the brain, and improved cognitive function in chronic SD mice. Our results identified gut microbiota as a driver in chronic SD and highlighted the NLRP3 inflammasome as a key regulator within the microbiota-gut-brain axis.
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“Chronic SD triggers gut microbiota alteration, leading to reduced mucus thickness and reduced levels of TJ proteins in mice colons, via NLRP3 inflammasome activation.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [646]
In the citing paper
“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 [646]
In the citing paper
“FMT from chronically sleep-deprived mice to control mice largely recapitulated the pathological changes observed in chronic SD.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [646]
In the citing paper
“This is accompanied by impaired BBB integrity, NLRP3 activation in the brain, microglial activation, and cognitive impairment.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [646]
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1 retracted
Wadhwa, M., Prabhakar, A., Anand, J. P., Ray, K., Prasad, D. N., Kumar, B., & Panjwani, U. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.08.004 · Cited by 82
RetractedNeuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286
Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008) · Diabetes · doi:10.2337/db07-1403 · Cited by 4,819
The NLRP3 Inflammasome: an overview of mechanisms of activation and regulation
Kelley, N., Jeltema, D., Duan, Y., & He, Y. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20133328 · Cited by 3,539
Mechanisms and Functions of Inflammasomes
Lamkanfi, M., & Dixit, V. M. (2014) · Cell · doi:10.1016/j.cell.2014.04.007 · Cited by 2,579
The gut microbiota–brain axis in behaviour and brain disorders
Morais, L. H., Schreiber, H. L., & Mazmanian, S. K. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-00460-0 · Cited by 2,149
Irwin, M. R., Olmstead, R., & Carroll, J. E. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.014 · Cited by 2,085
Short- and long-term health consequences of sleep disruption
Medic, G., Wille, M., & Hemels, M. (2017) · Nature and Science of Sleep · doi:10.2147/nss.s134864 · Cited by 1,776
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
Kang, J.-E., Lim, M. M., Bateman, R. J., Lee, J. J., Smyth, L. P., Cirrito, J. R., Fujiki, N., Nishino, S., & Holtzman, D. M. (2009) · Science · doi:10.1126/science.1180962 · Cited by 1,565
Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.019 · Cited by 1,382
The gut microbiome in neurological disorders
Cryan, J. F., O'Riordan, K. J., Sandhu, K., Peterson, V., & Dinan, T. G. (2020) · The Lancet Neurology · doi:10.1016/s1474-4422(19)30356-4 · Cited by 1,336
The sleep-deprived human brain
Krause, A. J., Simon, E. B., Mander, B. A., Greer, S. M., Saletin, J. M., Goldstein-Piekarski, A. N., & Walker, M. P. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.55 · Cited by 1,200
Wang, X., Sun, G., Feng, T., Zhang, J., Huang, X., Wang, T., Xie, Z., Chu, X., Yang, J., Wang, H., et al. (2019) · Cell Research · doi:10.1038/s41422-019-0216-x · Cited by 1,144
Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis
Shi, L., Chen, S.-J., Ma, M.-Y., Bao, Y.-P., Han, Y., Wang, Y.-M., Shi, J., Vitiello, M. V., & Lu, L. (2018) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2017.06.010 · Cited by 1,009
From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways
Rogers, G. B., Keating, D. J., Young, R. L., Wong, M.-L., Licinio, J., & Wesselingh, S. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.50 · Cited by 969
Gut Microbiota is Altered in Patients with Alzheimer’s Disease
Zhuang, Z.-Q., Shen, L.-L., Li, W.-W., Fu, X., Zeng, F., Gui, L., Lü, Y., Cai, M., Zhu, C., Tan, Y.-L., et al. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-180176 · Cited by 885
Sleep Deprivation and Activation of Morning Levels of Cellular and Genomic Markers of Inflammation
Irwin, M. R. (2006) · Archives of Internal Medicine · doi:10.1001/archinte.166.16.1756 · Cited by 850
The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology
Rutsch, A., Kantsjö, J. B., & Ronchi, F. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604179 · Cited by 821
The sleep-wake cycle regulates brain interstitial fluid tau in mice and CSF tau in humans
Holth, J. K., Fritschi, S. K., Wang, C., Pedersen, N. P., Cirrito, J. R., Mahan, T. E., Finn, M. B., Manis, M., Geerling, J. C., Fuller, P. M., et al. (2019) · Science · doi:10.1126/science.aav2546 · Cited by 813
Kim, M.-S., Kim, Y., Choi, H., Kim, W., Park, S., Lee, D., Kim, D. K., Kim, H. J., Choi, H., Hyun, D.-W., et al. (2020) · Gut · doi:10.1136/gutjnl-2018-317431 · Cited by 614
Poroyko, V. A., Carreras, A., Khalyfa, A., Khalyfa, A. A., Leone, V., Peris, E., Almendros, I., Gileles-Hillel, A., Qiao, Z., Hubert, N., et al. (2016) · Scientific Reports · doi:10.1038/srep35405 · Cited by 480
Sleep Loss Activates Cellular Inflammatory Signaling
Irwin, M. R., Wang, M., Ribeiro, D., Cho, H. J., Olmstead, R., Breen, E. C., Martinez-Maza, O., & Cole, S. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.004 · Cited by 467
Microbiota and the social brain
Sherwin, E., Bordenstein, S. R., Quinn, J. L., Dinan, T. G., & Cryan, J. F. (2019) · Science · doi:10.1126/science.aar2016 · Cited by 462
Altered Gut Microbiota in a Mouse Model of Alzheimer’s Disease
Zhang, L., Wang, Y., Xiayu, X., Shi, C., Chen, W., Song, N., Fu, X., Zhou, R., Xu, Y.-F., Huang, L., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170020 · Cited by 449
Sleep function: Toward elucidating an enigma
Krueger, J. M., Frank, M. G., Wisor, J. P., & Roy, S. (2016) · Sleep Medicine Reviews · doi:10.1016/j.smrv.2015.08.005 · Cited by 440
Short sleep duration and cardiometabolic risk: from pathophysiology to clinical evidence
Tobaldini, E., Fiorelli, E. M., Solbiati, M., Costantino, G., Nobili, L., & Montano, N. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0109-6 · Cited by 357
Sendler, M., van den Brandt, C., Glaubitz, J., Wilden, A., Golchert, J., Weiß, F. U., Homuth, G., Chama, L. L. D. F., Mishra, N., Mahajan, U. M., et al. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.09.040 · Cited by 352
Microbiota regulate social behaviour via stress response neurons in the brain
Wu, W., Adame, M. D., Liou, C.-W., Barlow, J. T., Lai, T.-T., Sharon, G., Schretter, C. E., Needham, B. D., Wang, M., Tang, W., et al. (2021) · Nature · doi:10.1038/s41586-021-03669-y · Cited by 351
Benedict, C., Vogel, H., Jonas, W., Woting, A., Blaut, M., Schürmann, A., & Cedernaes, J. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.10.003 · Cited by 324
Kreutzmann, J. C., Havekes, R., Abel, T., & Meerlo, P. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.04.053 · Cited by 309
Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn
Xu, K., Gao, X., Xia, G., Chen, M., Zeng, N., Wang, S., You, C., Tian, X., Di, H., Tang, W., et al. (2021) · Gut · doi:10.1136/gutjnl-2020-323263 · Cited by 308
Wang, Z., Chen, W.-H., Li, S.-X., He, Z.-M., Zhu, W.-L., Ji, Y.-B., Wang, Z., Zhu, X.-M., Yuan, K., Bao, Y.-P., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-021-01113-1 · Cited by 307
Roles and applications of probiotic Lactobacillus strains
Zhang, Z., Lv, J., Pan, L., & Zhang, Y. (2018) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-018-9217-9 · Cited by 296
Self-citationZhang, Y., Huang, R., Cheng, M., Wang, L., Chao, J., Li, J., Zheng, P., Xie, P., Zhang, Z., & Yao, H. (2019) · Microbiome · doi:10.1186/s40168-019-0733-3 · Cited by 263
The Role of Microglia and the Nlrp3 Inflammasome in Alzheimer's Disease
Hanslik, K. L., & Ulland, T. K. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.570711 · Cited by 236
Sutinen, E. M., Pirttilä, T., Anderson, G., Salminen, A., & Ojala, J. O. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-199 · Cited by 232
Mancuso, C., & Santangelo, R. (2018) · Pharmacological Research · doi:10.1016/j.phrs.2017.12.009 · Cited by 232
Li, J. J., Wang, B., Kodali, M. C., Chen, C., Kim, E., Patters, B. J., Lan, L.-B., Kumar, S., Wang, X., Yue, J., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1038-8 · Cited by 210
Shen, H., Guan, Q., Zhang, X., Yuan, C., Tan, Z., Zhai, L., Hao, Y., Gu, Y., & Han, C. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.109884 · Cited by 204
Liao, L., Schneider, K. M., Gálvez, E. J. C., Frissen, M., Marschall, H., Su, H., Hatting, M., Wahlstrom, A. M., Haybaeck, J., Puchas, P., et al. (2019) · Gut · doi:10.1136/gutjnl-2018-316670 · Cited by 176
Irwin, M. R., Witarama, T., Caudill, M. M., Olmstead, R., & Breen, E. C. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.017 · Cited by 168
Human and rat gut microbiome composition is maintained following sleep restriction
Zhang, S. L., Bai, L., Goel, N., Bailey, A., Jang, C. J., Bushman, F. D., Meerlo, P., Dinges, D. F., & Sehgal, A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620673114 · Cited by 139
Inflammasomes and intestinal inflammation
Zmora, N., Levy, M., Pevsner-Fishcer, M., & Elinav, E. (2017) · Mucosal Immunology · doi:10.1038/mi.2017.19 · Cited by 130
Pellegrini, C., Fornai, M., Antonioli, L., Blandizzi, C., & Calderone, V. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20122876 · Cited by 113
Robbins, R., Quan, S. F., Weaver, M. D., Bormes, G., Barger, L. K., & Czeisler, C. A. (2021) · Aging · doi:10.18632/aging.202591 · Cited by 104
Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome
Bowers, S. J., Vargas, F., González, A., He, S., Jiang, P., Dorrestein, P. C., Knight, R. D., Wright, K. P., Lowry, C. A., Fleshner, M., et al. (2020) · PLoS ONE · doi:10.1371/journal.pone.0229001 · Cited by 99
Acute Sleep-Wake Cycle Shift Results in Community Alteration of Human Gut Microbiome
Liu, Z., Wei, Z.-Y., Chen, J., Chen, K., Mao, X., Liu, Q., Sun, Y., Zhang, Z., Zhang, Y., Zhou, D., et al. (2020) · mSphere · doi:10.1128/msphere.00914-19 · Cited by 97
Self-citationAdolescent sleep restriction effects on cognition and mood
Short, M. A., & Chee, M. W. L. (2019) · Progress in brain research · doi:10.1016/bs.pbr.2019.02.008 · Cited by 90
Wang, K., Yao, Y., Zhu, X., Zhang, K., Zhou, F., & Zhu, L. (2016) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.21887 · Cited by 73
Park, E., Lee, Y., Kim, S. M., Park, G.-S., Lee, Y. H., Jeong, D. Y., Kang, J., & Lee, H. (2020) · Nutrients · doi:10.3390/nu12020542 · Cited by 70
Yin, M., Chen, Y., Zheng, H., Pu, T., Marshall, C., Wu, T., & Xiao, M. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.12.034 · Cited by 68
Chen, L., Huang, J., Yang, L., Zeng, X., Zhang, Y. P., Wang, X., Chen, M., Li, X., Zhang, Y., & Zhang, M. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.04.047 · Cited by 51
A brief period of sleep deprivation leads to subtle changes in mouse gut microbiota
Aidy, S. E., Bolsius, Y. G., Raven, F., & Havekes, R. (2019) · Journal of Sleep Research · doi:10.1111/jsr.12920 · Cited by 50
Gut Microbiota and Disorders of the Central Nervous System
Vuotto, C., Battistini, L., Caltagirone, C., & Borsellino, G. (2020) · The Neuroscientist · doi:10.1177/1073858420918826 · Cited by 37
Jia, L., Chen, H., Yang, J., Fang, X., Niu, W., Zhang, M., Li, J., Pan, X., Ren, Z., Sun, J., et al. (2019) · Innate Immunity · doi:10.1177/1753425919881502 · Cited by 35
Park, M., Park, E., Kim, S.-H., & Lee, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094444 · Cited by 18
Author Correction: Inflammasome signalling in brain function and neurodegenerative disease
Heneka, M. T., McManus, R. M., & Latz, E. (2019) · Nature reviews. Neuroscience · doi:10.1038/s41583-019-0137-1 · Cited by 17
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1 of the 59 references couldn’t be matched to a known paper.
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- Wood, 2018, Dementia: Peripheral inflammation could be a prodromal indicator of dementia, Nat. Rev. Neurol., 14, 127
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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
Cheng, J., Hu, H., Ju, Y., Liu, J., Wang, M., Liu, B., & Zhang, Y. (2024) · General Psychiatry · doi:10.1136/gpsych-2023-101374 · Cited by 234
Lu, S., Zhao, Q., Yu, G., Sun, Z., Li, W., Guo, S., & Zhang, A. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117207 · Cited by 191
Zhou, X., Ji, S., Chen, L., Liu, X., Deng, Y., You, Y., Wang, M., He, Q., Peng, B., Yang, Y., et al. (2024) · Microbiome · doi:10.1186/s40168-024-01826-9 · Cited by 92
Self-citationSun, J. F., Zeng, Q., Wu, Z., Huang, L., Sun, T., Liu, C., Zhang, B., Chen, C., & Wang, H. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00347 · Cited by 70
Metadata
- Authors
- Zhao, N., Chen, Q.-G., Chen, X., Liu, X.-T., Geng, F., Zhu, M.-M., Yan, F.-L., Zhang, Z.-J., & Ren, Q.-G.
- Affiliations
- Zhongda Hospital Southeast University (CN)
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2023-02
- Volume
- 108
- Pages
- 98-117
- ISSN
- 0889-1591 (ISSN-L)
- OpenAlex
- W4309880386
- Cited by
- 105
- References
- 59
- Citations by year
- 2026: 37 · 2025: 34 · 2024: 28 · 2023: 6
- FWCI
- 5.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gut dysbiosis, microbiota-gut-brain axis, NLRP3 inflammasome, chronic sleep deprivation, cognitive impairment, blood-brain barrier, intestinal barrier, neuroinflammation, synaptic dysfunction, hippocampus, gut microbiota transplantation, peripheral inflammation
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Hippocampus, Intestines, Sleep Deprivation, Mice, Inflammasomes, Cognitive Dysfunction, Dysbiosis
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