Volume 43 Issue 3
May  2022
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Zheng-Yu Yao, Xiao-Huan Li, Li Zuo, Qian Xiong, Wen-Ting He, Dong-Xu Li, Zhi-Fang Dong. Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats. Zoological Research, 2022, 43(3): 380-390. doi: 10.24272/j.issn.2095-8137.2022.023
Citation: Zheng-Yu Yao, Xiao-Huan Li, Li Zuo, Qian Xiong, Wen-Ting He, Dong-Xu Li, Zhi-Fang Dong. Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats. Zoological Research, 2022, 43(3): 380-390. doi: 10.24272/j.issn.2095-8137.2022.023

Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats

doi: 10.24272/j.issn.2095-8137.2022.023
Funds:  This work was supported by the National Natural Science Foundation of China (82071395, 91749116), Natural Science Foundation of Chongqing (cstc2021ycjh-bgzxm0186, cstc2020jcyj-zdxmX0004), Science and Technology Research Program of Chongqing Municipal Education Commission (KJZD-K201900403), and Innovation Research Group at Institutions of Higher Education in Chongqing (CXQTP19034)
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  • Corresponding author: E-mail: zfdong@cqmu.edu.cn
  • Received Date: 2022-02-24
  • Accepted Date: 2022-03-31
  • Published Online: 2022-03-31
  • Publish Date: 2022-05-18
  • Maternal sleep deprivation (MSD) is a global public health problem that affects the physical and mental development of pregnant women and their newborns. The latest research suggests that sleep deprivation (SD) disrupts the gut microbiota, leading to neuroinflammation and psychological disturbances. However, it is unclear whether MSD affects the establishment of gut microbiota and neuroinflammation in the newborns. In the present study, MSD was performed on pregnant Sprague-Dawley rats in the third trimester of pregnancy (gestational days 15–21), after which intestinal contents and brain tissues were collected from offspring at different postnatal days (P1, P7, P14, and P56). Based on microbial profiling, microbial diversity and richness increased in pregnant rats subjected to MSD, as reflected by the significant increase in the phylum Firmicutes. In addition, microbial dysbiosis marked by abundant Firmicutes bacteria was observed in the MSD offspring. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) showed that the expression levels of proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were significantly higher in the MSD offspring at adulthood (P56) than in the control group. Through Spearman correlation analysis, IL-1β and TNF-α were also shown to be positively correlated with Ruminococcus_1 and Ruminococcaceae_UCG-005 at P56, which may determine the microbiota-host interactions in MSD-related neuroinflammation. Collectively, these results indicate that MSD changes maternal gut microbiota and affects the establishment of neonatal gut microbiota, leading to neuroinflammation in MSD offspring. Therefore, understanding the role of gut microbiota during physiological development may provide potential interventions for cognitive dysfunction in MSD-impacted offspring.
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  • [1]
    Alvarenga TA, Aguiar MFP, Mazaro-Costa R, Tufik S, Andersen ML. 2013. Effects of sleep deprivation during pregnancy on the reproductive capability of the offspring. Fertility and Sterility, 100(6): 1752−1757. doi: 10.1016/j.fertnstert.2013.08.014
    Argeri R, Nishi EE, Volpini RA, Palma BD, Tufik S, Gomes GN. 2016. Sleep restriction during pregnancy and its effects on blood pressure and renal function among female offspring. Physiological Reports, 4(16): e12888. doi: 10.14814/phy2.12888
    Aswathy BS, Kumar VM, Gulia KK. 2018. The effects of rapid eye movement sleep deprivation during late pregnancy on newborns' sleep. Journal of Sleep Research, 27(2): 197−205. doi: 10.1111/jsr.12564
    Baratta AM, Kanyuch NR, Cole CA, Valafar H, Deslauriers J, Pocivavsek A. 2020. Acute sleep deprivation during pregnancy in rats: rapid elevation of placental and fetal inflammation and kynurenic acid. Neurobiology of Stress, 12: 100204. doi: 10.1016/j.ynstr.2019.100204
    Benedict C, Vogel H, Jonas W, Woting A, Blaut M, Schürmann A, et al. 2016. Gut microbiota and glucometabolic alterations in response to recurrent partial sleep deprivation in normal-weight young individuals. Molecular Metabolism, 5(12): 1175−1186. doi: 10.1016/j.molmet.2016.10.003
    Chassaing B, Gewirtz AT. 2014. Gut microbiota, low-grade inflammation, and metabolic syndrome. Toxicologic Pathology, 42(1): 49−53. doi: 10.1177/0192623313508481
    Chien MY, Chen HC. 2015. Poor sleep quality is independently associated with physical disability in older adults. Journal of Clinical Sleep Medicine, 11(3): 225−232. doi: 10.5664/jcsm.4532
    Crusell MKW, Hansen TH, Nielsen T, Allin KH, Rühlemann MC, Damm P, et al. 2018. Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum. Microbiome, 6(1): 89. doi: 10.1186/s40168-018-0472-x
    Du M, Liu J, Han N, Zhao ZL, Yang J, Xu XR, et al. 2021. Maternal sleep quality during early pregnancy, risk factors and its impact on pregnancy outcomes: a prospective cohort study. Sleep Medicine, 79: 11−18. doi: 10.1016/j.sleep.2020.12.040
    El Aidy S, Bolsius YG, Raven F, Havekes R. 2020. A brief period of sleep deprivation leads to subtle changes in mouse gut microbiota. Journal of Sleep Research, 29(6): e12920.
    Francis AP, Dominguez-Bello MG. 2019. Early-life microbiota perturbations and behavioral effects. Trends in Microbiology, 27(7): 567−569. doi: 10.1016/j.tim.2019.04.004
    Fricke EM, Elgin TG, Gong HY, Reese J, Gibson-Corley KN, Weiss RM, et al. 2018. Lipopolysaccharide-induced maternal inflammation induces direct placental injury without alteration in placental blood flow and induces a secondary fetal intestinal injury that persists into adulthood. American Journal of Reproductive Immunology, 79(5): e12816. doi: 10.1111/aji.12816
    Gao T, Wang ZX, Dong YL, Cao J, Lin RT, Wang XT, et al. 2019. Role of melatonin in sleep deprivation-induced intestinal barrier dysfunction in mice. Journal of Pineal Research, 67(1): e12574.
    García-Gómez E, González-Pedrajo B, Camacho-Arroyo I. 2013. Role of sex steroid hormones in bacterial-host interactions. BioMed Research International, 2013: 928290.
    Goyal D, Ali SA, Singh RK. 2021. Emerging role of gut microbiota in modulation of neuroinflammation and neurodegeneration with emphasis on Alzheimer's disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 106: 110112. doi: 10.1016/j.pnpbp.2020.110112
    Grech A, Collins CE, Holmes A, Lal R, Duncanson K, Taylor R, et al. 2021. Maternal exposures and the infant gut microbiome: a systematic review with meta-analysis. Gut Microbes, 13(1): 1897210. doi: 10.1080/19490976.2021.1897210
    Hajela N, Ramakrishna BS, Nair GB, Abraham P, Gopalan S, Ganguly NK. 2015. Gut microbiome, gut function, and probiotics: implications for health. Indian Journal of Gastroenterology, 34(2): 93−107. doi: 10.1007/s12664-015-0547-6
    Harskamp-van Ginkel MW, Ierodiakonou D, Margetaki K, Vafeiadi M, Karachaliou M, Kogevinas M, et al. 2020. Gestational sleep deprivation is associated with higher offspring body mass index and blood pressure. Sleep, 43(12): zsaa110. doi: 10.1093/sleep/zsaa110
    Herlemann DP, Labrenz M, Jürgens K, Bertilsson S, Waniek JJ, Andersson AF. 2011. Transitions in bacterial communities along the 2000 km salinity gradient of the Baltic Sea. The ISME Journal, 5(10): 1571−1579. doi: 10.1038/ismej.2011.41
    Hutchison BL, Stone PR, Mccowan LM, Stewart AW, Thompson JM, Mitchell EA. 2012. A postal survey of maternal sleep in late pregnancy. BMC Pregnancy and Childbirth, 12: 144. doi: 10.1186/1471-2393-12-144
    Jiang Y, Li PX, Zhong L, Liu BY, Gao XY, Ning L, et al. 2021. The influence of changes in work stressors and coping resources on sleep disturbances: evidence from the OHSPIW cohort study. Sleep, 44(8): zsab039. doi: 10.1093/sleep/zsab039
    John GK, Mullin GE. 2016. The gut microbiome and obesity. Current Oncology Reports, 18(7): 45. doi: 10.1007/s11912-016-0528-7
    Khalyfa A, Mutskov V, Carreras A, Khalyfa AA, Hakim F, Gozal D. 2014. Sleep fragmentation during late gestation induces metabolic perturbations and epigenetic changes in adiponectin gene expression in male adult offspring mice. Diabetes, 63(10): 3230−3241. doi: 10.2337/db14-0202
    Koliada A, Syzenko G, Moseiko V, Budovska L, Puchkov K, Perederiy V, et al. 2017. Association between body mass index and Firmicutes/Bacteroidetes ratio in an adult Ukrainian population. BMC Microbiology, 17(1): 120. doi: 10.1186/s12866-017-1027-1
    Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Bäckhed HK, et al. 2012. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell, 150(3): 470−480. doi: 10.1016/j.cell.2012.07.008
    Li DT, Wang P, Wang PP, Hu XS, Chen F. 2016. The gut microbiota: a treasure for human health. Biotechnology Advances, 34(7): 1210−1224. doi: 10.1016/j.biotechadv.2016.08.003
    Li YY, Zhang B, Zhou Y, Wang DM, Liu XC, Li L, et al. 2020. Gut microbiota changes and their relationship with inflammation in patients with acute and chronic insomnia. Nature and Science of Sleep, 12: 895−905. doi: 10.2147/NSS.S271927
    Lima ILB, Rodrigues AFAC, Bergamaschi CT, Campos RR, Hirata AE, Tufik S, et al. 2014. Chronic sleep restriction during pregnancy-repercussion on cardiovascular and renal functioning of male offspring. PLoS One, 9(11): e113075. doi: 10.1371/journal.pone.0113075
    Luczynski P, McVey Neufeld KA, Oriach CS, Clarke G, Dinan TG, Cryan JF. 2016. Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior. International Journal of Neuropsychopharmacology, 19(8): pyw020. doi: 10.1093/ijnp/pyw020
    Maki KA, Burke LA, Calik MW, Watanabe-Chailland M, Sweeney D, Romick-Rosendale LE, et al. 2020. Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats. Physiological Genomics, 52(7): 280−292. doi: 10.1152/physiolgenomics.00039.2020
    Matenchuk BA, Mandhane PJ, Kozyrskyj AL. 2020. Sleep, circadian rhythm, and gut microbiota. Sleep Medicine Reviews, 53: 101340. doi: 10.1016/j.smrv.2020.101340
    Mindell JA, Cook RA, Nikolovski J. 2015. Sleep patterns and sleep disturbances across pregnancy. Sleep Medicine, 16(4): 483−488. doi: 10.1016/j.sleep.2014.12.006
    Nam S, Whittemore R, Jung S, Latkin C, Kershaw T, Redeker NS. 2018. Physical neighborhood and social environment, beliefs about sleep, sleep hygiene behaviors, and sleep quality among African Americans. Sleep Health, 4(3): 258−264. doi: 10.1016/j.sleh.2018.03.002
    Nuriel-Ohayon M, Neuman H, Ziv O, Belogolovski A, Barsheshet Y, Bloch N, et al. 2019. Progesterone increases Bifidobacterium relative abundance during late pregnancy. Cell Reports, 27(3): 730−736.e3. doi: 10.1016/j.celrep.2019.03.075
    Okun ML, Coussons-Read ME. 2007. Sleep disruption during pregnancy: how does it influence serum cytokines?. Journal of Reproductive Immunology, 73(2): 158−165. doi: 10.1016/j.jri.2006.06.006
    Peng Y, Wang W, Tan T, He WT, Dong ZF, Wang YT, et al. 2016. Maternal sleep deprivation at different stages of pregnancy impairs the emotional and cognitive functions, and suppresses hippocampal long-term potentiation in the offspring rats. Molecular Brain, 9: 17. doi: 10.1186/s13041-016-0197-3
    Pien GW, Schwab RJ. 2004. Sleep disorders during pregnancy. Sleep, 27(7): 1405−1417. doi: 10.1093/sleep/27.7.1405
    Pires GN, Benedetto L, Cortese R, Gozal D, Gulia KK, Kumar VM, et al. 2021. Effects of sleep modulation during pregnancy in the mother and offspring: evidences from preclinical research. Journal of Sleep Research, 30(3): e13135.
    Poroyko VA, Carreras A, Khalyfa A, Khalyfa AA, Leone V, Peris E, et al. 2016. Chronic sleep disruption alters gut microbiota, induces systemic and adipose tissue inflammation and insulin resistance in Mice. Scientific Reports, 6: 35405. doi: 10.1038/srep35405
    Qi XY, Yun CY, Pang YL, Qiao J. 2021. The impact of the gut microbiota on the reproductive and metabolic endocrine system. Gut Microbes, 13(1): 1894070. doi: 10.1080/19490976.2021.1894070
    Radhakrishnan A, Aswathy BS, Kumar VM, Gulia KK. 2015. Sleep deprivation during late pregnancy produces hyperactivity and increased risk-taking behavior in offspring. Brain Research, 1596: 88−98. doi: 10.1016/j.brainres.2014.11.021
    Rao JJ, Qiao Y, Xie RN, Lin L, Jiang J, Wang CM, et al. 2021. Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain. Journal of Psychiatric Research, 137: 147−157. doi: 10.1016/j.jpsychires.2021.02.057
    Roque A, Ochoa-Zarzosa A, Torner L. 2016. Maternal separation activates microglial cells and induces an inflammatory response in the hippocampus of male rat pups, independently of hypothalamic and peripheral cytokine levels. Brain, Behavior, and Immunity, 55: 39−48. doi: 10.1016/j.bbi.2015.09.017
    Thomal JT, Palma BD, Ponzio BF, do Carmo Pinho Franco M, Zaladek-Gil F, Fortes ZB, et al. 2010. Sleep restriction during pregnancy: hypertension and renal abnormalities in young offspring rats. Sleep, 33(10): 1357−1362. doi: 10.1093/sleep/33.10.1357
    Tochitani S. 2021. Vertical transmission of gut microbiota: points of action of environmental factors influencing brain development. Neuroscience Research, 168: 83−94. doi: 10.1016/j.neures.2020.11.006
    Vecsey CG, Baillie GS, Jaganath D, Havekes R, Daniels A, Wimmer M, et al. 2009. Sleep deprivation impairs cAMP signalling in the hippocampus. Nature, 461(7267): 1122−1125. doi: 10.1038/nature08488
    Vecsey CG, Wimmer MEJ, Havekes R, Park AJ, Perron IJ, Meerlo P, et al. 2013. Daily acclimation handling does not affect hippocampal long-term potentiation or cause chronic sleep deprivation in Mice. Sleep, 36(4): 601−607. doi: 10.5665/sleep.2556
    Wang HX, Wang YP. 2016. Gut microbiota-brain axis. Chinese Medical Journal, 129(19): 2373−2380. doi: 10.4103/0366-6999.190667
    Wang Z, Chen WH, Li SX, He ZM, Zhu WL, Ji YB, et al. 2021. Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation. Molecular Psychiatry, 26(11): 6277−6292. doi: 10.1038/s41380-021-01113-1
    Yoo JY, Groer M, Dutra SVO, Sarkar A, Mcskimming DI. 2020. Gut microbiota and immune system interactions. Microorganisms, 8(10): 1587. doi: 10.3390/microorganisms8101587
    Yu YZ, Huang ZL, Dai CF, Du YH, Han HL, Wang YT, et al. 2018. Facilitated AMPAR endocytosis causally contributes to the maternal sleep deprivation-induced impairments of synaptic plasticity and cognition in the offspring rats. Neuropharmacology, 133: 155−162. doi: 10.1016/j.neuropharm.2018.01.030
    Zhao Q, Elson CO. 2018. Adaptive immune education by gut microbiota antigens. Immunology, 154(1): 28−37. doi: 10.1111/imm.12896
    Zhao QY, Peng C, Wu XH, Chen YB, Wang C, You ZL. 2014. Maternal sleep deprivation inhibits hippocampal neurogenesis associated with inflammatory response in young offspring rats. Neurobiology of Disease, 68: 57−65. doi: 10.1016/j.nbd.2014.04.008
    Zhao QY, Xie XF, Fan YH, Zhang JQ, Jiang W, Wu XH, et al. 2015. Phenotypic dysregulation of microglial activation in young offspring rats with maternal sleep deprivation-induced cognitive impairment. Scientific Reports, 5: 9513. doi: 10.1038/srep09513
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