Sleep deprivation-induced anxiety-like behaviors are associated with alterations in the gut microbiota and metabolites.
Microbiology spectrum
The present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance ( = 0.0002) and staying time in the central zone ( = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; = 0.028) and decreased levels of uridine ( = 0.018) and tryptophan ( = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of , , and decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS ( = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation. IMPORTANCE:The disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.
10.1128/spectrum.01437-23
From Alpha Diversity to Zzz: Interactions among sleep, the brain, and gut microbiota in the first year of life.
Schoch S F,Castro-Mejía J L,Krych L,Leng B,Kot W,Kohler M,Huber R,Rogler G,Biedermann L,Walser J C,Nielsen D S,Kurth S
Progress in neurobiology
Sleep disorders have been linked to alterations of gut microbiota composition in adult humans and animal models, but it is unclear how this link develops. With longitudinal assessments in 162 healthy infants, we present a so far unrecognized sleep-brain-gut interrelationship. First, we report a link between sleep habits and gut microbiota: daytime sleep is associated with bacterial diversity, and nighttime sleep fragmentation and variability are linked with bacterial maturity and enterotype. Second, we demonstrate a sleep-brain-gut link: bacterial diversity and enterotype are associated with sleep neurophysiology. Third, we show that the sleep-brain-gut link is relevant in development: sleep habits and bacterial markers predict behavioral-developmental outcomes. Our results demonstrate the dynamic interplay between sleep, gut microbiota, and the maturation of brain and behavior during infancy, which aligns with the newly emerging concept of a sleep-brain-gut axis. Importantly, sleep and gut microbiota represent promising health targets since both can be modified non-invasively. As many adult diseases root in early childhood, leveraging protective factors of adequate sleep and age-appropriate gut microbiota in infancy could constitute a health promoting factor across the entire human lifespan.
10.1016/j.pneurobio.2021.102208
Nutraceutical Capsules LL1 and Silymarin Supplementation Act on Mood and Sleep Quality Perception by Microbiota-Gut-Brain Axis: A Pilot Clinical Study.
Nutrients
Stress, unhealthy lifestyle, and sleep disturbance worsen cognitive function in mood disorders, prompting a rise in the development of integrative health approaches. The recent investigations in the gut-brain axis field highlight the strong interplay among microbiota, inflammation, and mental health. Thus, this study aimed to investigate a new nutraceutical formulation comprising prebiotics, minerals, and silymarin's impact on microbiota, inflammation, mood, and sleep quality. The study evaluated the LL1 + silymarin capsule supplementation over 180 days in overweight adults. We analyzed the fecal gut microbiota using partial 16S rRNA sequences, measured cytokine expression via CBA, collected anthropometric data, quality of life, and sleep questionnaire responses, and obtained plasma samples for metabolic and hormonal analysis at baseline (T0) and 180 days (T180) post-supplementation. Our findings revealed significant reshaping in gut microbiota composition at the phylum, genus, and species levels, especially in the butyrate-producer bacteria post-supplementation. These changes in gut microbiota were linked to enhancements in sleep quality, mood perception, cytokine expression, and anthropometric measures which microbiota-derived short-chain fatty acids might enhance. The supplementation tested in this study seems to be able to improve microbiota composition, reflecting anthropometrics and inflammation, as well as sleep quality and mood improvement.
10.3390/nu16183049
Obstructive Sleep Apnea-Induced Hypertension Is Associated With Increased Gut and Neuroinflammation.
Journal of the American Heart Association
Background Obstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension. We have demonstrated that OSA induces gut dysbiosis, and this dysbiotic microbiota contributes to hypertension. However, the mechanisms linking gut dysbiosis to blood pressure regulation remain unclear. Recent studies demonstrate that gut dysbiosis can induce a proinflammatory response of the host resulting in peripheral and neuroinflammation, key factors in the development of hypertension. We hypothesized that OSA induces inflammation in the gut that contributes to neuroinflammation and hypertension. Methods and Results OSA was induced in 8-week-old male rats. After 2 weeks of apneas, lymphocytes were isolated from aorta, brain, cecum, ileum, mesenteric lymph node, and spleen for flow cytometry. To examine the role of interleukin-17a, a monoclonal antibody was administered to neutralize interleukin-17a. Lymphocytes originating from the gut were tracked by labeling with carboxyfluorescein succinimidyl ester dye. OSA led to a significant decrease in T regulatory cells along with an increase in T helper (T) 17 cells in the ileum, cecum, and brain. Interleukin-17a neutralization significantly reduced blood pressure, increased T regulatory cells, and decreased T1 cells in the ileum, cecum, and brain of OSA rats. T1, T2, and T17 cells from the gut were found to migrate to the mesenteric lymph node, spleen, and brain with increased frequency in rats with OSA. Conclusions OSA induces a proinflammatory response in the gut and brain that involves interleukin-17a signaling. Gut dysbiosis may serve as the trigger for gut and neuroinflammation, and treatments to prevent or reverse gut dysbiosis may prove useful in reducing neuroinflammation and hypertension.
10.1161/JAHA.122.029218
Sleep regulation: The gut sets the threshold.
Current biology : CB
Sleep is regulated by many environmental factors including food availability and exposure to sensory stimuli. A recent study identifies a gut-brain axis that is activated by dietary proteins and inhibits sensory responsiveness, allowing animals to enter and maintain deep sleep.
10.1016/j.cub.2023.04.014
Washed microbiota transplantation improves sleep quality in patients with sleep disorder by the gut-brain axis.
Frontiers in neuroscience
Background:The clinical impact of washed microbiota transplantation (WMT) from healthy donors in sleep disorder (SD) patients is unclear. This study aimed to investigate the effect of WMT in SD patients. Methods:The clinical data were collected from patients with different indications receiving 1-3 courses of WMT, divided into two groups by 7 points of PSQI scale. The score of PQSI and SF-36 scale was used to assess the improvement in sleep quality and life quality among patients with sleep disorders following WMT. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of patients with sleep disorders before and after WMT. Results:WMT significantly improved sleep quality in patients with sleep disorder in the short and medium term. WMT significantly improved sleep latency, sleep time and total score in the short term. WMT significantly improved sleep quality and total score in the medium term. In terms of sleep quality and sleep latency, the improvement value also increased with the increase of treatment course, and the improvement effect of multiple treatment course was better than that of single and double treatment course. In the total score, the improvement effect of double and multiple treatment was better than that of single treatment. WMT also improved quality of life in the sleep disorder group. WMT significantly improved general health, vitality, social function and mental health in the short term. WMT significantly improved role-physical, general health, vitality, and mental health in the medium term. WMT regulated the disturbed gut microbiota in patients with sleep disorders. In the normal sleep group, WMT had no effect on the decline of sleep quality in the short, medium and long term, and had an improving effect on the quality of life. Conclusion:WMT could significantly improve sleep quality and life quality in patients with sleep disorders with no adverse events. The improvement in sleep quality resulting from WMT could lead to an overall enhancement in life quality. WMT could be a potentially effective treatment for patients with sleep disorders by regulating the gut microbiota.
10.3389/fnins.2024.1415167
Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects.
Open life sciences
Sleep is crucial for wellness, and emerging research reveals a profound connection to gut microbiota. This review explores the bidirectional relationship between gut microbiota and sleep, exploring the mechanisms involved and the therapeutic opportunities it presents. The gut-brain axis serves as a conduit for the crosstalk between gut microbiota and the central nervous system, with dysbiosis in the microbiota impairing sleep quality and . Diet, circadian rhythms, and immune modulation all play a part. Specific gut bacteria, like and , enhance sleep through serotonin and gamma-aminobutyric acid production, exemplifying direct microbiome influence. Conversely, sleep deprivation reduces beneficial bacteria, exacerbating dysbiosis. Probiotics, prebiotics, postbiotics, and fecal transplants show therapeutic potential, backed by animal and human research, yet require further study on safety and long-term effects. Unraveling this intricate link paves the way for tailored sleep therapies, utilizing microbiome manipulation to improve sleep and health. Accelerated research is essential to fully tap into this promising field for sleep disorder management.
10.1515/biol-2022-0910
Multiomics Analysis Reveals Aberrant Metabolism and Immunity Linked Gut Microbiota with Insomnia.
Microbiology spectrum
Studies have confirmed that insomnia is related to gut microbiota. Previous research suggests that immunity and metabolism are also associated with insomnia. However, to our knowledge, the integration of these factors has not been investigated in insomnia. Here, we explored the correlations across gut microbiota, serum metabolism, and inflammatory factors in insomnia. Our results showed that the composition and structure of gut microbiota and metabolism in insomnia patients were different from healthy controls. Compared to healthy controls, the relative abundances of , Streptococcus, and Lactobacillus crispatus were significantly increased in insomniacs. There were five metabolic pathways in insomniacs (glycerophospholipid metabolism; glutathione metabolism; nitrogen metabolism; alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis) significantly different between the two groups. Moreover, we found that IL-1β levels were significantly higher in insomnia patients while TNF-α was significantly reduced. We further identified that the changes in the level of IL-1β and TNF-α were associated with some specific bacteria and metabolites, such as Prevotella amnii, Prevotella buccalis, Prevotella timonensis, and Prevotella colorans. Mediation analysis further determined that the immune factors and metabolites could mediate the relationship between gut microbes and insomnia. Our study indicated that systematic inflammation and metabolites might be a pathway linking the gut microbiome with insomnia. These findings provide new insights and a better understanding of gut microbiota's role in insomnia as well as potential novel microbiome-related etiologies for insomnia.
10.1128/spectrum.00998-22
Sleep loss impairs intestinal stem cell function and gut homeostasis through the modulation of the GABA signalling pathway in Drosophila.
Cell proliferation
Sleep is essential for maintaining health. Indeed, sleep loss is closely associated with multiple health problems, including gastrointestinal disorders. However, it is not yet clear whether sleep loss affects the function of intestinal stem cells (ISCs). Mechanical sleep deprivation and sss mutant flies were used to generate the sleep loss model. qRT-PCR was used to measure the relative mRNA expression. Gene knock-in flies were used to observe protein localization and expression patterns. Immunofluorescence staining was used to determine the intestinal phenotype. The shift in gut microbiota was observed using 16S rRNA sequencing and analysis. Sleep loss caused by mechanical sleep deprivation and sss mutants disturbs ISC proliferation and intestinal epithelial repair through the brain-gut axis. In addition, disruption of SSS causes gut microbiota dysbiosis in Drosophila. As regards the mechanism, gut microbiota and the GABA signalling pathway both partially played a role in the sss regulation of ISC proliferation and gut function. The research shows that sleep loss disturbed ISC proliferation, gut microbiota, and gut function. Therefore, our results offer a stem cell perspective on brain-gut communication, with details on the effect of the environment on ISCs.
10.1111/cpr.13437
The relationship between gut microbiota and insomnia: a bi-directional two-sample Mendelian randomization research.
Frontiers in cellular and infection microbiology
Introduction:Insomnia is the second most common mental health issue, also is a social and financial burden. Insomnia affects the balance between sleep, the immune system, and the central nervous system, which may raise the risk of different systemic disorders. The gut microbiota, referred to as the "second genome," has the ability to control host homeostasis. It has been discovered that disruption of the gut-brain axis is linked to insomnia. Methods:In this study, we conducted MR analysis between large-scale GWAS data of GMs and insomnia to uncover potential associations. Results:Ten GM taxa were detected to have causal associations with insomnia. Among them, class , genus , genus , genus , genus , and order were linked to a higher risk of insomnia. In reverse MR analysis, we discovered a causal link between insomnia and six other GM taxa. Conclusion:It suggested that the relationship between insomnia and intestinal flora was convoluted. Our findings may offer beneficial biomarkers for disease development and prospective candidate treatment targets for insomnia.
10.3389/fcimb.2023.1296417
Sleep apnoea, gut dysbiosis and cognitive dysfunction.
The FEBS journal
Sleep disorders are becoming increasingly common, and their distinct effects on physical and mental health require elaborate investigation. Gut dysbiosis (GD) has been reported in sleep-related disorders, but sleep apnoea is of particular significance because of its higher prevalence and chronicity. Cumulative evidence has suggested a link between sleep apnoea and GD. This review highlights the gut-brain communication axis that is mediated via commensal microbes and various microbiota-derived metabolites (e.g. short-chain fatty acids, lipopolysaccharide and trimethyl amine N-oxide), neurotransmitters (e.g. γ-aminobutyric acid, serotonin, glutamate and dopamine), immune cells and inflammatory mediators, as well as the vagus nerve and hypothalamic-pituitary-adrenal axis. This review also discusses the pathological role underpinning GD and altered gut bacterial populations in sleep apnoea and its related comorbid conditions, particularly cognitive dysfunction. In addition, the review examines the preclinical and clinical evidence, which suggests that prebiotics and probiotics may potentially be beneficial in sleep apnoea and its comorbidities through restoration of eubiosis or gut microbial homeostasis that regulates neural, metabolic and immune responses, as well as physiological barrier integrity via the gut-brain axis.
10.1111/febs.16960
The relationship between irritable bowel syndrome, the gut microbiome, and obstructive sleep apnea: the role of the gut-brain axis.
Sleep & breathing = Schlaf & Atmung
Sleep disruption, especially that resulting from obstructive sleep apnea (OSA) - a widely prevalent sleep disorder - can lead to important systemic repercussions. We raise a subject of current interest, namely the possible relationship between sleep in general, OSA, and irritable bowel syndrome (IBS), an intestinal disease that can be made worse by stressful events. The intermittent hypoxia caused by OSA can induce alterations in the gut microbiota, which can lead to the dysregulation of the gut-brain axis and the worsening of IBS. This may be considered to be a circular relationship, with OSA playing a crucial role in the worsening of bowel symptoms, which in turn have a negative effect on sleep. Thus, based on previous evidence, we suggest that improving sleep quality could be a key to disrupting this relationship of IBS aggravation and OSA.
10.1007/s11325-023-02898-x
Oral quercetin nanoparticles in hydrogel microspheres alleviate high-altitude sleep disturbance based on the gut-brain axis.
International journal of pharmaceutics
High-altitude sleep disturbance is a common symptom of acute mountain sickness, which can be alleviated via modulation of the gut-brain axis. Quercetin (Que) is used to modulate gut microbiota and serves as a potential drug to regulate the gut-brain axis, but the poor solubility and bioavailability affect its biological functions. Here, Que nanoparticles (QNPs) were prepared with zein using an antisolvent method, and QNP-loaded calcium alginate hydrogel microspheres (QNP@HMs) were prepared using electrospinning technology to improve the gastrointestinal stability and intestinal adhesion of QNPs. In the mouse model of high-altitude sleep disturbance, oral administration of QNP@HMs before the mice entering high altitude prolonged sleep duration, improved blood cell recovery, spontaneous behavior and short-term memory, and reduced such inflammation factors as TNF-α and iNOS. Moreover, QNP@HMs enhanced the abundance of probiotics in the gut, including Lactobacillus and Lachnospira, and reduced intestinal inflammation. However, in the mice after gut sterilization by long-term oral antibiotics, QNP@HMs showed no therapeutic effect. QNP@HMs are a promising medication for the prevention of high-altitude sleep disturbance based on the gut-brain axis.
10.1016/j.ijpharm.2024.124225
Postweaning intermittent sleep deprivation enhances defensive attack in adult female mice via the microbiota-gut-brain axis.
Progress in neuro-psychopharmacology & biological psychiatry
Sleep is one of the most important physiological activities in life and promotes the growth and development of an individual. In modern society, sleep deprivation (SD), especially among adolescents, has become a common phenomenon. However, long-term SD severely affected adolescents' neurodevelopment leading to abnormal behavioral phenotypes. Clinical studies indicated that sleep problems caused increased aggressive behavior in adolescents. Aggressive behavior was subordinate to social behaviors, in which defensive attack was often the last line for survival. Meanwhile, increasing studies shown that gut microbiota regulated social behaviors by affecting specific brain regions via the gut-brain axis. However, whether postweaning intermittent SD is related to defensive attack in adulthood, and if so, whether it is mediated by the microbiota-gut-brain axis are still elusive. Combined with microbial sequencing and hippocampal metabolomics, the present study mainly investigated the long-term effects of postweaning intermittent SD on defensive attack in adult mice. Our study demonstrated that postweaning intermittent SD enhanced defensive attack and impaired long-term memory formation in adult female mice. Moreover, microbial sequencing and LC-MS analysis showed that postweaning intermittent SD altered the gut microbial composition and the hippocampal metabolic profile in female mice, respectively. Our attention has been drawn to the neuroactive ligand-receptor interaction pathway and related metabolites. In conclusion, our findings provide a new perspective on the relationship of early-life SD and defensive attack in adulthood, and also highlight the importance of sleep in early-life, especially in females.
10.1016/j.pnpbp.2023.110915
Regulation of sleep disorders in patients with traumatic brain injury by intestinal flora based on the background of brain-gut axis.
Frontiers in neuroscience
Objective:This study investigates whether people with sleep disorders following traumatic brain injury exhibit altered intestinal flora. The changes may allow us to gain a better understanding of the role of intestinal flora in patients with sleep disorders after traumatic brain injury, which may give us insights into curing the sleep disorder after traumatic brain injury (TBI). Method:We analyzed the intestinal microbial colony structure in the feces of the 28 patients in the normal sleep group and the sleep disorder group by 16SrDNAsequencing technology. The bioinformatics method was used to analyze the intestinal flora change in the v3-v4 region of patients with biorhythm disorder and to observe the difference between the two groups. Results:Group grouping comparison and analysis of the evolutionary cladistic map showed the intestinal flora of patients with normal sleep after TBI was mainly Bacilli and Lactobacillales, while that of patients with sleep disorders was mainly Lachnospiraceae and Bacteroidales. The histogram of group value distribution by grouping comparison and analysis showed that Lachnospiraceae, Bacteroidales, Bacteroidia, and Bacteroidetes were dominant in the sleep disorder group. A relative abundance map of species with significant differences by group grouping comparison showed the main manifestations of intestinal flora are Firmicutes, Bacilli, Lactobacillales, Streptococcaceae, and Bacteroidetes. The normal sleep group was dominated by Bacilli, Lactobacillales, Streptococcus, and Veillonella, while in the sleep disorder group, Lachnospiraceae, Bacteroidales, Bacteroidia, and Bacteroidetes were the main species. It was found that there were also significant differences in intestinal flora abundance between the two groups after TBI. After statistics processing, it was compared with the normal sleep group, Lactobacillus, Streptococcus, Oribacterium and Rothia, Actinomyces, Streptophyta, TM7-3 bacteria, and Serratia, showing a significant reduction in the sleep disorder group ( < 0.05). However, Odoribacter, Lachnospiraceae, and Bilophila increased significantly ( < 0.05). Conclusion:The sleep disorders of patients after TBI can be closely related to intestinal flora disturbance, and its internal mechanism needs further study. Intestinal flora has the potential to be a new therapeutic target.
10.3389/fnins.2022.934822
CCFM1025 Improves Sleep Quality via Regulating the Activity of the HPA Axis: A Randomized Clinical Trial.
Nutrients
Psychobiotics, a newly identified category of probiotics primarily targeting the gut-brain axis, exhibit tremendous potential in improving sleep quality. In this study, the clinical trial was registered in advance (identifier: NO. ChiCTR2300067806). Forty participants who were diagnosed with stress-induced insomnia were chosen and randomly divided into two groups: one received CCFM1025 at a dose of 5 × 10 CFU ( = 20), while the other was administered a placebo ( = 20), over a period of four weeks. The results revealed that compared to the placebo group (pre: M = 10.10, SD = 2.292; post: M = 8.650, SD = 2.793; pre vs. post: F (1, 38) = 15.41, = 0.4316), the CCFM1025-treated group exhibited a significant decrease in Pittsburgh Sleep Quality Index (PSQI) scores from baseline (pre: M = 11.60, SD = 3.169; post: M = 7.750, SD = 3.697, F (1, 38) = 15.41, = 0.0007). Furthermore, the administration of CCFM1025 was associated with a more pronounced reduction in stress marker concentrations. This effect could potentially be linked to changes in serum metabolites induced by the probiotic treatment, notably daidzein. In conclusion, CCFM1025 demonstrates promise as a psychobiotic strain for enhancing sleep quality.
10.3390/nu15214700
Maternal sleep deprivation induces gut microbial dysbiosis and neuroinflammation in offspring rats.
Zoological research
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 . In addition, microbial dysbiosis marked by abundant 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 and 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.
10.24272/j.issn.2095-8137.2022.023
Associations between gut microbiota and sleep: a two-sample, bidirectional Mendelian randomization study.
Frontiers in microbiology
Introduction:Previous research has reported that the gut microbiota performs an essential role in sleep through the microbiome-gut-brain axis. However, the causal association between gut microbiota and sleep remains undetermined. Methods:We performed a two-sample, bidirectional Mendelian randomization (MR) analysis using genome-wide association study summary data of gut microbiota and self-reported sleep traits from the MiBioGen consortium and UK Biobank to investigate causal relationships between 119 bacterial genera and seven sleep-associated traits. We calculated effect estimates by using the inverse-variance weighted (as the main method), maximum likelihood, simple model, weighted model, weighted median, and MR-Egger methods, whereas heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier method, Cochran's Q statistics, and MR-Egger regression. Results:In forward MR analysis, inverse-variance weighted estimates concluded that the genetic forecasts of relative abundance of 42 bacterial genera had causal effects on sleep-associated traits. In the reverse MR analysis, sleep-associated traits had a causal effect on 39 bacterial genera, 13 of which overlapped with the bacterial genera in the forward MR analysis. Discussion:In conclusion, our research indicates that gut microbiota may be involved in the regulation of sleep, and conversely, changes in sleep-associated traits may also alter the abundance of gut microbiota. These findings suggest an underlying reciprocal causal association between gut microbiota and sleep.
10.3389/fmicb.2023.1236847
[The interactions along the microbiota-gut-brain axis in the regulation of circadian rhythms, sleep mechanisms and disorders].
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
The bidirectional relationship between cerebral structures and the gastrointestinal tract involving the microbiota embraces the scientific concept of the microbiota-gut-brain axis. The gut microbiome plays an important role in many physiological and biochemical processes of the human body, in the immune response and maintenance of homeostasis, as well as in the regulation of circadian rhythms. There is a relationship between the higher prevalence of a number of neurological disorders, sleep disorders and changes in the intestinal microbiota, which actualizes the study of the complex mechanisms of such correlation for the development of new treatment and prevention strategies. Environmental factors associated with excessive light exposure can aggravate the gut dysbiosis of intestinal microflora, and as a result, lead to sleep disturbances. This review examines the integrative mechanisms of sleep regulation associated with the gut microbiota (the role of neurotransmitters, short-chain fatty acids, unconjugated bile acids, bacterial cell wall components, cytokines). Taking into account the influence of gut dysbiosis as a risk factor in the development of various diseases, the authors systematize key aspects and modern scientific data on the importance of microflora balance to ensure optimal interaction along the microbiota-gut-brain axis in the context of the regulatory role of the sleep-wake cycle and its disorders.
10.17116/jnevro202412405279
"Visceral Consciousness": The Gut-Brain Axis in Sleep and Sleeplessness in Britain and America, 1850-1914.
Hussey Kristin D
Bulletin of the history of medicine
Sleeplessness was a quotidian yet challenging problem for medical practitioners in Britain and America in the nineteenth and early twentieth centuries. While physiologists endeavored to unravel the secrets of sleep by examining the brain, in the clinic doctors looked to the gut as a site through which sleeplessness was both caused and cured. This article explores the gut-brain axis in medical literature on sleep and sleep loss in this period. It argues that despite the lack of a coherent understanding of the gut-brain connection, the digestive system was central to how physiologists and clinicians approached sleeplessness. It employs Victorian physician Joseph Mortimer Granville's (1833-1900) concept of "visceral consciousness" to better understand the varied and often contradictory explanatory constellations that emerged to elucidate the role of digestion in sleeplessness.
10.1353/bhm.2021.0033
Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives.
Nature communications
The microbiota-gut-brain axis has been suggested to play an important role in Parkinson's disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.
10.1038/s41467-023-38248-4
An emerging role of astrocytes in aging/neuroinflammation and gut-brain axis with consequences on sleep and sleep disorders.
Ageing research reviews
Understanding the role of astrocytes in the central nervous system has changed dramatically over the last decade. The accumulating findings indicate that glial cells are involved not only in the maintenance of metabolic and ionic homeostasis and in the implementation of trophic functions but also in cognitive functions and information processing in the brain. Currently, there are some controversies regarding the role of astrocytes in complex processes such as aging of the nervous system and the pathogenesis of age-related neurodegenerative diseases. Many findings confirm the important functional role of astrocytes in age-related brain changes, including sleep disturbance and the development of neurodegenerative diseases and particularly Alzheimer's disease. Until recent years, neurobiological research has focused mainly on neuron-glial interactions, in which individual astrocytes locally modulate neuronal activity and communication between neurons. The review considers the role of astrocytes in the physiology of sleep and as an important "player" in the development of neurodegenerative diseases. In addition, the features of the astrocytic network reorganization during aging are discussed.
10.1016/j.arr.2022.101775
Anorexigenic Effects of Intermittent Hypoxia on the Gut-Brain Axis in Sleep Apnea Syndrome.
International journal of molecular sciences
Sleep apnea syndrome (SAS) is a breathing disorder characterized by recurrent episodes of upper-airway collapse, resulting in intermittent hypoxia (IH) during sleep. Experimental studies with animals and cellular models have indicated that IH leads to attenuation of glucose-induced insulin secretion from pancreatic β cells and to enhancement of insulin resistance in peripheral tissues and cells, such as the liver (hepatocytes), adipose tissue (adipocytes), and skeletal muscles (myocytes), both of which could lead to obesity. Although obesity is widely recognized as a major factor in SAS, it is controversial whether the development of SAS could contribute directly to obesity, and the effect of IH on the expression of appetite regulatory genes remains elusive. Appetite is regulated appropriately by both the hypothalamus and the gut as a gut-brain axis driven by differential neural and hormonal signals. In this review, we summarized the recent epidemiological findings on the relationship between SAS and feeding behavior and focused on the anorexigenic effects of IH on the gut-brain axis by the IH-induced up-regulation of proopiomelanocortin and cocaine- and amphetamine-regulated transcript in neuronal cells and the IH-induced up-regulation of peptide YY, glucagon-like peptide-1 and neurotensin in enteroendocrine cells and their molecular mechanisms.
10.3390/ijms23010364
Gut microbiota: A new target of traditional Chinese medicine for insomnia.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
All species have a physiological need for sleep, and sleep is crucial for the preservation and restoration of many physiological processes in the body. Recent research on the effects of gut microbiota on brain function has produced essential data on the relationship between them. It has been discovered that dysregulation of the gut-brain axis is related to insomnia. Certain metabolites of gut microbiota have been linked to insomnia, and disturbances in gut microbiota can worsen insomnia. Traditional Chinese medicine (TCM) has unique advantages for the treatment of insomnia. Taking the gut microbiota as the target and determining the scientific relevance of TCM to the prevention and treatment of insomnia may lead to new concepts for the treatment of sleep disorders and improve the therapeutic effect of sleep. Taking the gut microbiota as an entry point, this paper reviews the relationship between gut microbiota and TCM, the relationship between gut microbiota and insomnia, the mechanism by which gut microbiota regulate sleep, and the mechanism by which TCM regulates gut microbiota for insomnia prevention and treatment. This review provides new ideas for the prevention and treatment of insomnia through TCM and new ideas for drug development.
10.1016/j.biopha.2023.114344
The interplay between sleep and gut microbiota.
Han Mengqi,Yuan Shiying,Zhang Jiancheng
Brain research bulletin
Sleep is a universal physiological need in all species and is essential for the maintenance and recovery of various physiological functions of the body. In late years, the gut microbiota (GM), a vast and extraordinarily complex ecosystem located in human gastrointestinal tract that oversees an array of critical bodily functions, has become a popular focus among researchers. Accumulated evidences in this field have revealed that it exerts important roles in the regulation of some biological characteristics, especially metabolic, immunological and neurobehavioral functions. With the increasing comprehension of brain-gut axis, a bidirectional communication channel linking the brain and gut, the roles of GM in sleep are paid much attention to. Evidences have shown that the GM is essential for the maintenance of normal sleep physiology. In turn, it has also been demonstrated that the abnormal sleep patterns and duration affect the composition, diversity and function of the GM through the brain-gut-microbiota axis (BGMA). Present contributions have described several underlying factors that could be involved in the BGMA in sleep, such as the immune system, the vagus nerve, the neuroendocrine system, and bacterial metabolites. Furthermore, several interventions targeting the GM have been proved to be beneficial for amelioration of sleep problems. On this basis, in this review, we aim to explore the interaction between sleep and GM, and elucidate the therapeutic microbiota manipulations with potential promoting effects on sleep quality.
10.1016/j.brainresbull.2021.12.016
Dietary fiber ameliorates sleep disturbance connected to the gut-brain axis.
Food & function
Circadian rhythms play an important role in maintaining normal physiological and psychological functions of the body, including regulating sleep patterns. External factors such as poor eating habits and work and rest patterns of modern people can disrupt the circadian rhythm, resulting in sleep disorders such as difficulty falling asleep and frequent waking up. The gut flora uses the "gut-brain axis" as a bridge to establish a connection with sleep, mainly including immune pathways, neural pathways, and endocrine pathways. Meanwhile, this article emphasizes that increasing the intake of dietary fiber in the daily dietary structure is beneficial for ameliorating sleep disorders. This is attributed to the metabolism of dietary fiber in the colon, increasing the type and quantity of probiotics and their representative metabolites, short-chain fatty acids (SCFAs), in the gut. They modulate sleep disorders by significantly improving the damaged gut barrier, stimulating the secretion of sleep cytokines, inhibiting inflammatory pathways, and increasing serotonin secretion. These provide new strategies for improving human sleep disorders from the perspective of the gut microbiota.
10.1039/d2fo01178f
Microbiota and sleep: awakening the gut feeling.
Sen Paromita,Molinero-Perez Alicia,O'Riordan Kenneth J,McCafferty Cian P,O'Halloran Ken D,Cryan John F
Trends in molecular medicine
Various lifestyle and environmental factors are known to influence sleep. Increasingly, evidence points to a role for the microbiota in regulating brain and behaviour. This article explores how the microbiota-gut-brain axis affects sleep directly and indirectly. We summarize the possible molecular mechanisms underlying sleep-microbiome interactions and discuss how various factors interact with the gut microbiota to influence sleep. Furthermore, we present the current evidence of alterations of the microbiota-gut-brain axis in various sleep disorders and pathologies where comorbid sleep disturbances are common. Since manipulating the gut microbiota could potentially improve sleep, we outline ways in which this can be achieved.
10.1016/j.molmed.2021.07.004
The Microbiota-Gut-Brain Axis in Metabolic Syndrome and Sleep Disorders: A Systematic Review.
Nutrients
BACKGROUND:Over recent decades, a growing body of evidence has emerged linking the composition of the gut microbiota to sleep regulation. Interestingly, the prevalence of sleep disorders is commonly related to cardiometabolic comorbidities such as diabetes, impaired lipid metabolism, and metabolic syndrome (MetS). In this complex scenario, the role of the gut-brain axis as the main communicating pathway between gut microbiota and sleep regulation pathways in the brain reveals some common host-microbial biomarkers in both sleep disturbances and MetS. As the biological mechanisms behind this complex interacting network of neuroendocrine, immune, and metabolic pathways are not fully understood yet, the present systematic review aims to describe common microbial features between these two unrelated chronic conditions. RESULTS:This systematic review highlights a total of 36 articles associating the gut microbial signature with MetS or sleep disorders. Specific emphasis is given to studies evaluating the effect of dietary patterns, dietary supplementation, and probiotics on MetS or sleep disturbances. CONCLUSIONS:Dietary choices promote microbial composition and metabolites, causing both the amelioration and impairment of MetS and sleep homeostasis.
10.3390/nu16030390
The microbiota-gut-brain axis in sleep disorders.
Sleep medicine reviews
Sleep is a complex physiological process and is a critical determinant of physical and mental health. In the past decades, significant progress has been made in understanding the neural mechanisms of sleep and awakening. However, the initiation and maintenance of the sleep-wake cycle is regulated not only by the central system but is also affected by signals from peripheral tissues. Growing evidence shows that the microbiota-gut-brain axis contributes to the regulation of sleep behavior both directly and indirectly and may play a critical role in the etiology and pathogenesis of sleep disorders. Sleep deprivation leads to dysfunction of gut microbiota and sleep disorders are accompanied by altered gut microbiota composition. In this review, we describe the bidirectional relationships between sleep and gut microbiota and summarize the abnormal characteristics of gut bacteria in distinct conditions including sleep disturbances, sleep disorders and sleep disorders comorbid with neuropsychiatric disorders. We also examine the potential routes of microbiota-gut-brain axis in sleep and gut microbiome interactions, including metabolic, immune, and neural pathways, and propose microbiota-targeted interventions for improving sleep. Manipulating gut microbiota may be a promising avenue for the development of novel interventions for sleep disorders.
10.1016/j.smrv.2022.101691