Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation

Microbiome, Journal Year: 2023, Volume and Issue: 11(1)

Published: Jan. 31, 2023

Abstract 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 intestinal microbiota disturbances caused by sleep deprivation (SD). The present study further explored the mechanism which exogenous prevents SD-induced impairments. Here, we established fecal transplantation, Aeromonas colonization LPS or butyrate supplementation tests to evaluate role of its metabolites in alleviating impairment. Results Transplantation SD-gut into normal mice induced microglia overactivation neuronal apoptosis hippocampus, decline, colonic disorder, manifesting as increased levels decreased Lachnospiraceae_NK4A136 butyrate. All these events were reversed with transplantation SD + melatonin-gut microbiota. Colonization addition produced an inflammatory response hippocampus spatial mice. These changes melatonin, accompanied LPS. Butyrate administration sleep-deprived restored responses In vitro, BV2 cells, was improved supplementation. This ameliorative effect blocked pretreatment MCT1 inhibitor HDAC3 agonist but mimicked TLR4 p-P65 antagonists. Conclusions Gut microbes their mediate effects on A feasible downregulates constituent upregulates colon. lessen through crosstalk between TLR4/NF-κB MCT1/ signaling pathways.

Language: Английский

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Inflammatory pathways in Alzheimer’s disease mediated by gut microbiota

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 68, P. 101317 - 101317

Published: March 10, 2021

Language: Английский

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Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD)

Brain Behavior and Immunity, Journal Year: 2022, Volume and Issue: 108, P. 245 - 254

Published: Dec. 6, 2022

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental characterized by communication and social behavior deficits. The presence of restricted repetitive behaviors often accompanies these deficits, characteristics can range from mild to severe. past several decades have seen significant rise in the prevalence ASD. etiology ASD remains unknown; however, genetic environmental risk factors play role. Multiple hypotheses converge suggest that neuroinflammation, or at least interaction between immune neural systems, may be involved some cases groups. Repeated evidence innate dysfunction has been ASD, associated with worsening behaviors. This includes data circulating myeloid cells brain resident macrophages/microglia both human animal models. comprehensive review presents recent findings including aberrant cellular function, microglia activation.

Language: Английский

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Inhibition of inflammatory microglia by dietary fiber and short-chain fatty acids

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Feb. 16, 2023

Microglia play a vital role maintaining brain homeostasis but can also cause persistent neuroinflammation. Short-chain fatty acids (SCFAs) produced by the intestinal microbiota have been suggested to regulate microglia inflammation indirectly signaling through gut-brain axis or directly reaching brain. The present work evaluated anti-inflammatory effects of SCFAs on lipopolysaccharide (LPS)-stimulated from mice fed inulin, soluble fiber that is fermented produce in vivo, and applied primary vitro. Feeding inulin increased cecum plasma collected hepatic portal vein. isolated stimulated with LPS vitro secreted less tumor necrosis factor α (TNF-α) compared not given inulin. Additionally, when were injected i.p LPS, ex vivo secretion TNF-α was lower than LPS. Similarly, treatment acetate butyrate either alone combination downregulated cytokine production being additive. reduced histone deacetylase activity nuclear factor-κB translocation after Whereas expression SCFA receptors Ffar2 Ffar3 detected single-cell RNA sequencing analysis, transporters Mct1 Mct4 were. Nevertheless, inhibiting monocarboxylate did interfere SCFAs, suggesting if gut it likely an epigenetic mechanism following diffusion.

Language: Английский

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Mechanisms of Short-Chain Fatty Acids Derived from Gut Microbiota in Alzheimer's Disease

Aging and Disease, Journal Year: 2022, Volume and Issue: 13(4), P. 1252 - 1252

Published: Jan. 1, 2022

Short-chain fatty acids (SCFAs) are important metabolites derived from the gut microbiota through fermentation of dietary fiber. SCFAs participate a number physiological and pathological processes in human body, such as host metabolism, immune regulation, appetite regulation. Recent studies on gut-brain interaction have shown that mediators interactions involved occurrence development many neurodegenerative diseases, including Alzheimer's disease. This review summarizes current research potential roles mechanisms AD. First, we introduce metabolic distribution, specific receptors signaling pathways body. The concentration levels AD patient/animal models then summarized. In addition, illustrate effects cognitive level, features (Aβ tau) neuroinflammation Finally, analyze translational value therapeutic targets for treatment

Language: Английский

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The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 165, P. 115276 - 115276

Published: Aug. 4, 2023

Short-chain fatty acids (SCFAs) derived from the fermentation of carbohydrates by gut microbiota play a crucial role in regulating host physiology. Among them, acetate, propionate, and butyrate are key players various biological processes. Recent research has revealed their significant functions immune inflammatory responses. For instance, reduces development interferon-gamma (IFN-γ) generating cells while promoting regulatory T (Treg) cells. Propionate inhibits initiation Th2 response dendritic (DCs). Notably, SCFAs have an inhibitory impact on polarization M2 macrophages, emphasizing immunomodulatory properties potential for therapeutics. In animal models asthma, both propionate suppress pathway, thus reducing allergic airway inflammation. Moreover, dysbiosis leading to altered SCFA production been implicated prostate cancer progression. trigger autophagy promote accelerating tumor advancement. Manipulating microbiota- producing holds promise treatment. Additionally, enhance expression hypoxia-inducible factor 1 (HIF-1) blocking histone deacetylase, resulting increased antibacterial effectors improved macrophage-mediated elimination microorganisms. This highlights antimicrobial defense mechanisms. comprehensive review provides in-depth analysis latest functional aspects underlying mechanisms relation macrophage activities wide range diseases, including infectious diseases cancers. By elucidating intricate interplay between functions, this aims contribute understanding therapeutic pave way future interventions targeting disease management.

Language: Английский

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Short chain fatty acids, a possible treatment option for autoimmune diseases

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 163, P. 114763 - 114763

Published: April 25, 2023

Gut microbiota can interact with the immune system through its metabolites. Short-chain fatty acids (SCFAs), as one of most abundant metabolites resident gut play an important role in this crosstalk. SCFAs (acetate, propionate, and butyrate) regulate nearly every type cell gut's repertoire regarding their development function. work several pathways to impose protection towards colonic health against local or systemic inflammation. Additionally, a regulation non-immune that slow autoimmunity either systematically situ. The present study aims summarize current knowledge on immunomodulatory roles association between autoimmune disorders such celiac disease (CD), inflammatory bowel (IBD), rheumatoid arthritis (RA), multiple sclerosis (MS), lupus erythematosus (SLE), 1 diabetes (T1D) other immune-mediated diseases, uncovering brand-new therapeutic possibility prevent treat autoimmunity.

Language: Английский

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Role of microglia in stroke

Glia, Journal Year: 2024, Volume and Issue: 72(6), P. 1016 - 1053

Published: Jan. 4, 2024

Abstract Microglia play key roles in the post‐ischemic inflammatory response and damaged tissue removal reacting rapidly to disturbances caused by ischemia working restore lost homeostasis. However, modified environment, encompassing ionic imbalances, disruption of crucial neuron–microglia interactions, spreading depolarization, generation danger signals from necrotic neurons, induce morphological phenotypic shifts microglia. This leads them adopt a proinflammatory profile heighten their phagocytic activity. From day three post‐ischemia, macrophages infiltrate core while microglia amass at periphery. Further, inflammation prompts metabolic shift favoring glycolysis, pentose‐phosphate shunt, lipid synthesis. These shifts, combined with intake, drive droplet biogenesis, fuel anabolism, enable proliferation. Proliferating release trophic factors contributing protection repair. some accumulate lipids persistently transform into dysfunctional potentially harmful foam cells. Studies also showed that either display impaired apoptotic cell clearance, or eliminate synapses, viable endothelial Yet, it will be essential elucidate viability engulfed cells, features local extent damage, temporal sequence. Ischemia provides rich variety region‐ injury‐dependent stimuli for microglia, evolving time generating distinct phenotypes including those exhibiting traits others showing pro‐repair features. Accurate profiling phenotypes, alongside more precise understanding associated conditions, is necessary step serve as potential foundation focused interventions human stroke.

Language: Английский

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Anti-neuroinflammatory Effect of Short-Chain Fatty Acid Acetate against Alzheimer’s Disease via Upregulating GPR41 and Inhibiting ERK/JNK/NF-κB

Journal of Agricultural and Food Chemistry, Journal Year: 2020, Volume and Issue: 68(27), P. 7152 - 7161

Published: June 25, 2020

Alzheimer's disease (AD) is a high-incidence neurodegenerative in the elderly. Acetate (Ace) short-chain fatty acid (SCFA) with neuroprotective activity. The purpose of this study was to investigate effects and its possible mechanisms SCFA Ace on AD. A male APP/PS1 transgenic mouse given intragastric administration for 4 weeks. Cognitive function microglia activation mice were assessed. Furthermore, pretreated amyloid-β (Aβ)-induced BV2 microglia, levels CD11b, COX-2, G-protein-coupled receptor 41 (GPR41) phosphorylation ERK, JNK, NF-κB p65 determined. Our results revealed that significantly attenuated cognitive impairment decreased CD11b level mice. Moreover, inhibited p65, JNK COX-2 interleukin 1β Aβ-stimulated microglia. Finally, increased GPR41 cells. finding indicated exerted antineuroinflammatory via upregulation suppression ERK/JNK/NF-κB pathway, which might provide an alternative therapy strategy

Language: Английский

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Current Evidence on the Role of the Gut Microbiome in ADHD Pathophysiology and Therapeutic Implications

Nutrients, Journal Year: 2021, Volume and Issue: 13(1), P. 249 - 249

Published: Jan. 16, 2021

Studies suggest that the bidirectional relationship existent between gut microbiome (GM) and central nervous system (CNS), or so-called microbiome–gut–brain axis (MGBA), is involved in diverse neuropsychiatric diseases children adults. In pediatric age, most studies have focused on patients with autism. However, evidence of role played by MGBA attention deficit/hyperactivity disorder (ADHD), common neurodevelopmental childhood, still scanty heterogeneous. This review aims to provide current functioning ADHD specific omega-3 polyunsaturated fatty acids (ω-3 PUFAs) this interaction, as well potential GM a therapeutic target for ADHD. We will explore: (1) communication pathways CNS; (2) changes composition adolescents association pathophysiology; (3) influence ω-3 PUFA imbalance characteristically found ADHD; (4) interaction circadian rhythm regulation, sleep disorders are frequently comorbid (5) finally, we evaluate recent use probiotics

Language: Английский

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