Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations.
Thaiss Christoph A,Levy Maayan,Korem Tal,Dohnalová Lenka,Shapiro Hagit,Jaitin Diego A,David Eyal,Winter Deborah R,Gury-BenAri Meital,Tatirovsky Evgeny,Tuganbaev Timur,Federici Sara,Zmora Niv,Zeevi David,Dori-Bachash Mally,Pevsner-Fischer Meirav,Kartvelishvily Elena,Brandis Alexander,Harmelin Alon,Shibolet Oren,Halpern Zamir,Honda Kenya,Amit Ido,Segal Eran,Elinav Eran
Cell
The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.
10.1016/j.cell.2016.11.003
Probiotics, prebiotics and postbiotics for better sleep quality: a narrative review.
Beneficial microbes
There is a growing prevalence of sleep problems and insomnia worldwide, urging the development of new treatments to tackle this increase. Several studies have suggested that the gut microbiome might influence sleep quality. The gut microbiome affects the host's health via the production of metabolites and compounds with neuroactive and immunomodulatory properties, which include short-chain fatty acids, secondary bile acids and neurotransmitters. Several of these metabolites and compounds are independently known as wakefulness-promoting (serotonin, epinephrine, dopamine, orexin, histamine, acetylcholine, cortisol) or sleep-promoting (gamma-aminobutyric acid, melatonin). The primary aim of this review was to evaluate the potential of pro-, pre- and postbiotic treatments to improve sleep quality. Additionally, we aimed to evaluate whether each of the treatments could ameliorate stress and anxiety, which are known to bidirectionally correlate with sleep problems. Lastly, we provided a mechanistic explanation for our findings. A literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar to compare all human trials that met our inclusion criteria and were published before November 2021. We furthermore discussed relevant findings from animal experiments to provide a mechanistic insight. While several studies found that sleep latency, sleep length, and cortisol levels improved after pro-, pre- or postbiotic treatment, others did not show any significant improvements for sleep quality, stress, or anxiety. These discrepancies can be explained by between-study variations in study designs, study populations, treatments, type and level of distress, and sex differences. We conclude that the trials discussed provide some evidence for prebiotics, postbiotics, and traditional probiotics, such as those belonging to lactobacilli and bifidobacteria, to improve sleep quality and stress, but stronger evidence might be found in the future after implementing the methodological adjustments that are suggested in this review.
10.3920/BM2021.0122
Microglia regulate sleep through calcium-dependent modulation of norepinephrine transmission.
Nature neuroscience
Sleep interacts reciprocally with immune system activity, but its specific relationship with microglia-the resident immune cells in the brain-remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving G-coupled GPCRs, intracellular Ca signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia G signaling strongly promoted sleep, whereas pharmacological blockade of G-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12-G activation elevated microglia intracellular Ca, and blockade of this Ca elevation largely abolished the G-induced sleep increase. Microglia Ca level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12-G activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.
10.1038/s41593-023-01548-5
Gut Microbiota as an Objective Measurement for Auxiliary Diagnosis of Insomnia Disorder.
Liu Bingdong,Lin Weifeng,Chen Shujie,Xiang Ting,Yang Yifan,Yin Yulong,Xu Guohuan,Liu Zhihong,Liu Li,Pan Jiyang,Xie Liwei
Frontiers in microbiology
Insomnia is a type of sleep disorder which is associated with various diseases' development and progression, such as obesity, type II diabetes and cardiovascular diseases. Recent investigation of the gut-brain axis enhances our understanding of the role of the gut microbiota in brain-related diseases. However, whether the gut microbiota is associated with insomnia remains unknown. In the present investigation, leveraging the 16S rDNA amplicon sequencing of V3-V4 region and the novel bioinformatic analysis, it was demonstrated that between insomnia and healthy populations, the composition, diversity and metabolic function of the gut microbiota are significantly changed. Other than these, redundancy analysis, co-occurrence analysis and PICRUSt underpin the gut taxa composition, signaling pathways, and metabolic functions perturbed by insomnia disorder. Moreover, random forest together with cross-validation identified two signature bacteria, which could be used to distinguish the insomnia patients from the healthy population. Furthermore, based on the relative abundance and clinical sleep parameter, we constructed a prediction model utilizing artificial neural network (ANN) for auxiliary diagnosis of insomnia disorder. Overall, the aforementioned study provides a comprehensive understanding of the link between the gut microbiota and insomnia disorder.
10.3389/fmicb.2019.01770
Sleep Deprivation and Gut Microbiota Dysbiosis: Current Understandings and Implications.
International journal of molecular sciences
Gut microbiota comprises the microbial communities inhabiting our gastrointestinal (GI) tracts. Accordingly, these complex communities play a fundamental role in many host processes and are closely implicated in human health and diseases. Sleep deprivation (SD) has become increasingly common in modern society, partly owing to the rising pressure of work and the diversification of entertainment. It is well documented that sleep loss is a significant cause of various adverse outcomes on human health including immune-related and metabolic diseases. Furthermore, accumulating evidence suggests that gut microbiota dysbiosis is associated with these SD-induced human diseases. In this review, we summarize the gut microbiota dysbiosis caused by SD and the succedent diseases ranging from the immune system and metabolic system to various organs and highlight the critical roles of gut microbiota in these diseases. The implications and possible strategies to alleviate SD-related human diseases are also provided.
10.3390/ijms24119603
Sleep, circadian rhythm, and gut microbiota.
Matenchuk Brittany A,Mandhane Piush J,Kozyrskyj Anita L
Sleep medicine reviews
From asthma and heart disease to diabetes and obesity, the human microbiome plays a role in the pathogenesis of each chronic health condition plaguing today's society. Recent work has shown that the gut microbiota and its metabolites exhibit diurnal rhythmicity which predominantly respond to the feeding/fasting cycle. Persistent jet lag, an obesogenic diet, and clock gene deficiency can dampen the oscillatory nature of gut bacterial composition, which can subsequently be rescued by time restricted feeding. Contrastingly, gut microbial metabolites influence central and hepatic clock gene expression and sleep duration in the host and regulate body composition through circadian transcription factors. Both sleep fragmentation and short sleep duration are associated with gut dysbiosis which may be due to activation of the HPA-axis. Metabolic disturbances associated with sleep loss may in fact be mediated through the overgrowth of specific gut bacteria. Reciprocally, the end products of bacterial species which grow in response to sleep loss are able to induce fatigue. Furthermore, probiotic supplementation has been found to improve subjective sleep quality. Sleep quality and duration may be an important target for supporting healthy gut microbiota composition, but the cyclic nature of this relationship should not be overlooked.
10.1016/j.smrv.2020.101340
Gut microbiota: Candidates for a novel strategy for ameliorating sleep disorders.
Critical reviews in food science and nutrition
The aim of this review was to evaluate the feasibility of treating sleep disorders using novel gut microbiota intervention strategies. Multiple factors can cause sleep disorders, including an imbalance in the gut microbiota. Studies of the microbiome-gut-brain axis have revealed bidirectional communication between the central nervous system and gut microbes, providing a more comprehensive understanding of mood and behavioral regulatory patterns. Changes in the gut microbiota and its metabolites can stimulate the endocrine, nervous, and immune systems, which regulate the release of neurotransmitters and alter the activity of the central nervous system, ultimately leading to sleep disorders. Here, we review the main factors affecting sleep, discuss possible pathways and molecular mechanisms of the interaction between sleep and the gut microbiota, and compare common gut microbiota intervention strategies aimed at improving sleep physiology.
10.1080/10408398.2023.2228409
A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.
The Lancet. Infectious diseases
BACKGROUND:Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS:In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS:Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION:Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING:Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.
10.1016/S1473-3099(23)00685-0
Gut microbiota mediate vascular dysfunction in a murine model of sleep apnoea: effect of probiotics.
The European respiratory journal
BACKGROUND:Obstructive sleep apnoea (OSA) is a chronic prevalent condition characterised by intermittent hypoxia (IH), and is associated with endothelial dysfunction and coronary artery disease (CAD). OSA can induce major changes in gut microbiome diversity and composition, which in turn may induce the emergence of OSA-associated morbidities. However, the causal effects of IH-induced gut microbiome changes on the vasculature remain unexplored. Our objective was to assess if vascular dysfunction induced by IH is mediated through gut microbiome changes. METHODS:Faecal microbiota transplantation (FMT) was conducted on C57BL/6J naïve mice for 6 weeks to receive either IH or room air (RA) faecal slurry with or without probiotics (VSL#3). In addition to 16S rRNA amplicon sequencing of their gut microbiome, FMT recipients underwent arterial blood pressure and coronary artery and aorta function testing, and their trimethylamine -oxide (TMAO) and plasma acetate levels were determined. Finally, C57BL/6J mice were exposed to IH, IH treated with VSL#3 or RA for 6 weeks, and arterial blood pressure and coronary artery function assessed. RESULTS:Gut microbiome taxonomic profiles correctly segregated IH from RA in FMT mice and the normalising effect of probiotics emerged. Furthermore, IH-FMT mice exhibited increased arterial blood pressure and TMAO levels, and impairments in aortic and coronary artery function (p<0.05) that were abrogated by probiotic administration. Lastly, treatment with VSL#3 under IH conditions did not attenuate elevations in arterial blood pressure or CAD. CONCLUSIONS:Gut microbiome alterations induced by chronic IH underlie, at least partially, the typical cardiovascular disturbances of sleep apnoea and can be mitigated by concurrent administration of probiotics.
10.1183/13993003.00002-2022
Gut Microbiota Changes and Their Relationship with Inflammation in Patients with Acute and Chronic Insomnia.
Nature and science of sleep
PURPOSE:The major purpose of this study was to detect the changes in gut microbiota composition and inflammatory cytokines production associated with acute and chronic insomnia. This study also evaluated the relationship between gut microbiota changes and increased inflammatory cytokines in insomnia patients. PATIENTS AND METHODS:Outpatients with acute and chronic insomnia (aged 26-55 years; n=20 and 38, respectively) and age/gender-matched healthy controls (n=38) were recruited from a southern China region. Participants' gut microbiome, plasma cytokines, and self-reported sleep quality and psychopathological symptoms were measured. RESULTS:The gut microbiomes of insomnia patients compared with healthy controls were characterized by lower microbial richness and diversity, depletion of anaerobes, and short-chain fatty acid (SCFA)-producing bacteria, and an expansion of potential pathobionts. and were signature bacteria for distinguishing acute insomnia patients from healthy controls, while and were signature bacteria for distinguishing chronic insomnia patients from healthy controls. Acute/chronic insomnia-related signature bacteria also showed correlations with these patients' self-reported sleep quality and plasma IL-1β. CONCLUSION:These findings suggest that insomnia symptomology, gut microbiota, and inflammation may be interrelated in complex ways. Gut microbiota may serve as an important indicator for auxiliary diagnosis of insomnia and provide possible new therapeutic targets in the field of sleep disorders.
10.2147/NSS.S271927
Relationship between sleep disorders and gut dysbiosis: what affects what?
Neroni Bruna,Evangelisti Melania,Radocchia Giulia,Di Nardo Giovanni,Pantanella Fabrizio,Villa Maria Pia,Schippa Serena
Sleep medicine
Sleep plays a fundamental role in maintaining good psycho-physical health, it can influence hormone levels, mood, and weight. Recent studies, focused on the interconnection between intestinal microbiome and sleep disorders, have shown the growing importance of a healthy and balanced intestinal microbiome for the hosts health. Normally, gut microbiota and his host are linked by mutualistic relationship, that in some conditions, can be compromised by shifts in microbiota's composition, called dysbiosis. Both sleep problems and dysbiosis of the gut microbiome can lead to metabolic disorders and, in this review, we will explore what is present in literature on the link between sleep pathologies and intestinal dysbiosis.
10.1016/j.sleep.2021.08.003
Exploring the relationship between social jetlag with gut microbial composition, diet and cardiometabolic health, in the ZOE PREDICT 1 cohort.
European journal of nutrition
PURPOSE:In this study, we explore the relationship between social jetlag (SJL), a parameter of circadian misalignment, and gut microbial composition, diet and cardiometabolic health in the ZOE PREDICT 1 cohort (NCT03479866). METHODS:We assessed demographic, diet, cardiometabolic, stool metagenomics and postprandial metabolic measures (n = 1002). We used self-reported habitual sleep (n = 934) to calculate SJL (difference in mid-sleep time point of ≥ 1.5 h on week versus weekend days). We tested group differences (SJL vs no-SJL) in cardiometabolic markers and diet (ANCOVA) adjusting for sex, age, BMI, ethnicity, and socio-economic status. We performed comparisons of gut microbial composition using machine learning and association analyses on the species level genome bins present in at least 20% of the samples. RESULTS:The SJL group (16%, n = 145) had a greater proportion of males (39% vs 25%), shorter sleepers (average sleep < 7 h; 5% vs 3%), and were younger (38.4 ± 11.3y vs 46.8 ± 11.7y) compared to the no-SJL group. SJL was associated with a higher relative abundance of 9 gut bacteria and lower abundance of 8 gut bacteria (q < 0.2 and absolute Cohen's effect size > 0.2), in part mediated by diet. SJL was associated with unfavourable diet quality (less healthful Plant-based Diet Index), higher intakes of potatoes and sugar-sweetened beverages, and lower intakes of fruits, and nuts, and slightly higher markers of inflammation (GlycA and IL-6) compared with no-SJL (P < 0.05 adjusted for covariates); rendered non-significant after multiple testing adjustments. CONCLUSIONS:Novel associations between SJL and a more disadvantageous gut microbiome in a cohort of predominantly adequate sleepers highlight the potential implications of SJL for health.
10.1007/s00394-023-03204-x
When Rhythms Meet the Blues: Circadian Interactions with the Microbiota-Gut-Brain Axis.
Teichman Emily M,O'Riordan Kenneth J,Gahan Cormac G M,Dinan Timothy G,Cryan John F
Cell metabolism
The microbiota-gut-brain axis encompasses a bidirectional mode of communication between the microorganisms residing in our gut, and our brain function and behavior. The composition of the gut microbiota is subject to diurnal variation and is entrained by host circadian rhythms. In turn, a diverse microbiota is essential for optimal regulation of host circadian pathways. Disruption of the cyclical nature of this microbe-host interaction profoundly influences disease pathology and severity. This review aims to summarize current knowledge on this bidirectional relationship. Indeed, the past few years have revealed promising data regarding the relationship between the microbiota-gut-brain axis and circadian rhythms and how they act in concert to influence disease, but further research needs to be done to examine how they coalesce to modulate severity of, and risk for, certain diseases. Moreover, there is a need for a greater understanding of the molecular mechanisms underlying the close relationship between circadian-microbiome-brain interactions.
10.1016/j.cmet.2020.02.008
Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation.
Microbiome
BACKGROUND:Sleep loss is a serious global health concern. Consequences include memory deficits and gastrointestinal dysfunction. Our previous research showed that melatonin can effectively improve cognitive impairment and intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism by which exogenous melatonin prevents SD-induced cognitive impairments. Here, we established fecal microbiota transplantation, Aeromonas colonization and LPS or butyrate supplementation tests to evaluate the role of the intestinal microbiota and its metabolites in melatonin in alleviating SD-induced memory impairment. RESULTS: Transplantation of the SD-gut microbiota into normal mice induced microglia overactivation and neuronal apoptosis in the hippocampus, cognitive decline, and colonic microbiota disorder, manifesting as increased levels of Aeromonas and LPS and decreased levels of Lachnospiraceae_NK4A136 and butyrate. All these events were reversed with the transplantation of SD + melatonin-gut microbiota. Colonization with Aeromonas and the addition of LPS produced an inflammatory response in the hippocampus and spatial memory impairment in mice. These changes were reversed by supplementation with melatonin, accompanied by decreased levels of Aeromonas and LPS. Butyrate administration to sleep-deprived mice restored inflammatory responses and memory impairment. In vitro, LPS supplementation caused an inflammatory response in BV2 cells, which was improved by butyrate supplementation. This ameliorative effect of butyrate was blocked by pretreatment with MCT1 inhibitor and HDAC3 agonist but was mimicked by TLR4 and p-P65 antagonists. CONCLUSIONS: Gut microbes and their metabolites mediate the ameliorative effects of melatonin on SD-induced cognitive impairment. A feasible mechanism is that melatonin downregulates the levels of Aeromonas and constituent LPS and upregulates the levels of Lachnospiraceae_NK4A136 and butyrate in the colon. These changes lessen the inflammatory response and neuronal apoptosis in the hippocampus through crosstalk between the TLR4/NF-κB and MCT1/ HDAC3 signaling pathways. Video Abstract.
10.1186/s40168-022-01452-3
Gut microbiota composition is associated with narcolepsy type 1.
Lecomte Alexandre,Barateau Lucie,Pereira Pedro,Paulin Lars,Auvinen Petri,Scheperjans Filip,Dauvilliers Yves
Neurology(R) neuroimmunology & neuroinflammation
OBJECTIVE:To test the hypothesis that narcolepsy type 1 (NT1) is related to the gut microbiota, we compared the microbiota bacterial communities of patients with NT1 and control subjects. METHODS:Thirty-five patients with NT1 (51.43% women, mean age 38.29 ± 19.98 years) and 41 controls (57.14% women, mean age 36.14 ± 12.68 years) were included. Stool samples were collected, and the fecal microbiota bacterial communities were compared between patients and controls using the well-standardized 16S rRNA gene amplicon sequencing approach. We studied alpha and beta diversity and differential abundance analysis between patients and controls, and between subgroups of patients with NT1. RESULTS:We found no between-group differences for alpha diversity, but we discovered in NT1 a link with NT1 disease duration. We highlighted differences in the global bacterial community structure as assessed by beta diversity metrics even after adjustments for potential confounders as body mass index (BMI), often increased in NT1. Our results revealed differential abundance of several operational taxonomic units within Bacteroidetes, , and between patients and controls, but not after adjusting for BMI. CONCLUSION:We provide evidence of gut microbial community structure alterations in NT1. However, further larger and longitudinal multiomics studies are required to replicate and elucidate the relationship between the gut microbiota, immunity dysregulation and NT1.
10.1212/NXI.0000000000000896
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
Gut microbiota modulates the inflammatory response and cognitive impairment induced by sleep deprivation.
Molecular psychiatry
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.
10.1038/s41380-021-01113-1
supplementation prevents cognitive impairment in sleep-deprived mice by modulating microglial engulfment of synapses.
Gut microbes
The microbiome-gut-brain axis plays a crucial role in many neurological diseases, including mild cognitive impairment. Sleep deprivation (SD) induces cognitive decline accompanied by alterations in the gut microbiota. However, the role of gut microbiota alterations in SD-induced cognitive dysfunction and the underlying mechanisms remain unclear. Here, we found that dysbiosis of the gut microbiota following pretreatment with broad-spectrum antibiotics worsens SD-induced cognitive impairment in mice. Fecal microbiota transplantation from SD mice to healthy mice induced cognitive impairment. Additionally, the abundance of () in the mouse gut microbiota was significantly reduced after 7 days of SD. pretreatment alleviated cognitive dysfunction and prevented synaptic reduction in the hippocampus in SD mice. pretreatment inhibited extensive microglial activation and synaptic engulfment in the hippocampus of SD mice. Metabolomics analysis revealed that pretreatment increased the serum acetate and butanoic acid levels in SD mice. Finally, pretreatment with short-chain fatty acids (SCFAs) inhibited microglial synaptic engulfment and prevented neuronal synaptic loss in SD mice and primary microglia-neuron co-culture following LPS stimulation. Together, our findings illustrate that gut dysbiosis plays an essential role in SD-induced cognitive impairment by activating microglial engulfment at synapses. supplementation may be a novel preventative strategy for SD-induced cognitive dysfunction, by increasing SCFAs production and maintaining microglial homeostasis.
10.1080/19490976.2023.2252764