Fructus gardeniae ameliorates anxiety-like behaviors induced by sleep deprivation via regulating hippocampal metabolomics and gut microbiota

Dong, Lei; Wang, Qian-fei; Liu, Ying; Yuan, Zhenshuang; Liu, Zhiliang; Guo, Jianhua; Li, Xin; Zhang, Weichao; Tao, Yulei; Mei, Jianqiang

doi:10.3389/fcimb.2023.1167312

Cited by 3 publications

(3 citation statements)

References 87 publications

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“…For instance, fructus gardeniae, known to alleviate anxiety symptoms caused by sleep deprivation, has been linked to the modulation of intestinal flora. In sleep-deprived mice, PPP was significantly enriched in the group treated with a low dose of gardeniae but not in those receiving a high dose [ 44 ]. This suggests a positive correlation between PPP enrichment and sleep deprivation, aligning with the findings of our study.…”

Section: Discussionmentioning

confidence: 99%

Causality Investigation between Gut Microbiome and Sleep-Related Traits: A Bidirectional Two-Sample Mendelian Randomization Study

Zhai,

Song,

Liu

et al. 2024

Genes

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Recent research has highlighted associations between sleep and microbial taxa and pathways. However, the causal effect of these associations remains unknown. To investigate this, we performed a bidirectional two-sample Mendelian randomization (MR) analysis using summary statistics of genome-wide association studies (GWAS) from 412 gut microbiome traits (N = 7738) and GWAS studies from seven sleep-associated traits (N = 345,552 to 386,577). We employed multiple MR methods to assess causality, with Inverse Variance Weighted (IVW) as the primary method, alongside a Bonferroni correction ((p < 2.4 × 10−4) to determine significant causal associations. We further applied Cochran’s Q statistical analysis, MR-Egger intercept, and Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) for heterogeneity and pleiotropy assessment. IVW estimates revealed 79 potential causal effects of microbial taxa and pathways on sleep-related traits and 45 inverse causal relationships, with over half related to pathways, emphasizing their significance. The results revealed two significant causal associations: genetically determined relative abundance of pentose phosphate decreased sleep duration (p = 9.00 × 10−5), and genetically determined increase in fatty acid level increased the ease of getting up in the morning (p = 8.06 × 10−5). Sensitivity analyses, including heterogeneity and pleiotropy tests, as well as a leave-one-out analysis of single nucleotide polymorphisms, confirmed the robustness of these relationships. This study explores the potential causal relationships between sleep and microbial taxa and pathways, offering novel insights into their complex interplay.

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Section: Discussionmentioning

confidence: 99%

Causality Investigation between Gut Microbiome and Sleep-Related Traits: A Bidirectional Two-Sample Mendelian Randomization Study

Zhai,

Song,

Liu

et al. 2024

Genes

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“…The abundance of the genus Lachnospiraceae is significantly increased in the gut of mice deprived of brief insomnia (37). In rats treated with gardenia for insomnia, the GM showed changes, including a reduction in the genus Lachnospiraceae (38). In a study that evaluated the GM characteristics of early and late sleepers, the "owls" exhibited an increase in the genus Lachnospiraceae (39).…”

Section: Discussionmentioning

confidence: 99%

A bidirectional Mendelian randomization study investigating the causal role between gut microbiota and insomnia

Yang,

Su,

Zhang

et al. 2023

Front. Neurol.

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BackgroundIt has emerged that disturbances of the gut microbiota (GM) are linked to insomnia. However, the causality of the observed associations remains uncertain.MethodsWe conducted a two-sample Mendelian randomization analysis based on genome-wide association study data to explore the possible causal link between GM and insomnia. The GM data were from the MiBioGen consortium, while the summary statistics of insomnia were obtained from the FinnGen consortium R9 release data. Cochran’s Q statistics were used to analyze instrumental variable heterogeneity.ResultsAccording to the inverse variance weighted estimates, the family Ruminococcaceae (odds ratio = 1.494, 95% confidence interval:1.004–2.223, p = 0.047) and the genus Lachnospiraceae (odds ratio = 1.726, 95% confidence interval: 1.191–2.501, p = 0.004) play a role in insomnia risk. In contrast, the genus Flavonifractor (odds ratio = 0.596, 95% confidence interval: 0.374–0.952, p = 0.030) and the genus Olsenella (odds ratio = 0.808, 95% confidence interval: 0.666–0.980, p = 0.031) tended to protect against insomnia. According to the reverse MR analysis, insomnia can also alter GM composition. Instrumental variables were neither heterogeneous nor horizontal pleiotropic.ConclusionIn conclusion, our Mendelian randomization study provides evidence of a causal relationship between GM and insomnia. The identified GM may be promising gut biomarkers and new therapeutic targets for insomnia. This investigation also provides a foundation for future studies examining the influence of GM on sleep disorders beyond insomnia, with potential implications for redefining the mechanisms governing sleep regulation.

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“…82 In addition, its comprehensiveness, sensitivity and unbiased nature make it especially suitable for capturing subtle physiological changes. Previous metabolomic analyses have been more focused on less invasive body fluids such as urine, 83 plasma 84 and saliva 85 to screen for potential metabolic biomarkers for evaluating sleep status. Recent studies have also attempted to explore cerebral metabolic changes caused by heterogeneous sleep disruption protocols, but these have yielded inconsistent results.…”

Section: Sleep Deprivation Alters Whole Brain Metabolic Profilesmentioning

confidence: 99%

Sustained microglial activation and accelerated elimination of dendritic spines during acute sleep deprivation and restoration

Liu,

Xu,

et al. 2023

TIL

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<p>Sleep is a fundamental physiological condition strongly regulated by a variety of neuroanatomical and neurochemical systems. Recent studies have indicated that catch-up sleep falls short of effectiveness to counteract the negative consequences of sleep debt however, the underlying mechanisms remain poorly understood. In this study, by using various transgenic fluorescent mouse models as well as techniques including intravital two-photon imaging and immunofluorescence staining of brain sections, we have documented morphological and functional changes of microglia during acute sleep deprivation (ASD) and subsequent short-term recovery sleep (RS). In these cerebral resident immune cells, we observed sustained microglial de-ramification, reduction of process motility and enhancement of microglial phagocytosis across brain regions. Given the intimate connections between microglia activity and neuronal plasticity, we also investigated synaptic plasticity and demonstrated an accelerated elimination of dendritic spines during both ASD and subsequent RS. Furthermore, untargeted metabolomic analyses revealed extensive whole-brain metabolic changes during ASD, and that a substantial number of metabolites and pathways failed to recover within a short period of RS. It is tempting to speculate that the disturbed cerebral metabolic homeostasis contributes to the sustained microglial activation and accelerated elimination of dendritic spines during this process. This study reveals the adverse effects of sleep loss on neuroimmunomodulation and neuronal plasticity, and implicates potential mechanisms underlying how irregular sleep schedules lead to neurological disorders.</p>

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Fructus gardeniae ameliorates anxiety-like behaviors induced by sleep deprivation via regulating hippocampal metabolomics and gut microbiota

Cited by 3 publications

References 87 publications

Causality Investigation between Gut Microbiome and Sleep-Related Traits: A Bidirectional Two-Sample Mendelian Randomization Study

Causality Investigation between Gut Microbiome and Sleep-Related Traits: A Bidirectional Two-Sample Mendelian Randomization Study

A bidirectional Mendelian randomization study investigating the causal role between gut microbiota and insomnia

Sustained microglial activation and accelerated elimination of dendritic spines during acute sleep deprivation and restoration

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