The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

FEBS Journal, Journal Year: 2024, Volume and Issue: unknown

Published: March 1, 2024

Huntington's disease (HD) is a currently incurable neurogenerative disorder and typically characterized by progressive movement (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which depression), peripheral symptoms gastrointestinal dysfunction). There are no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some hold promising potential. HD subjects often burdened chronic diarrhea, constipation, esophageal gastric inflammation, susceptibility to diabetes. Our understanding the microbiota–gut–brain axis its infancy growing evidence from preclinical clinical studies suggests role gut microbial population imbalance (gut dysbiosis) pathophysiology. The brain can communicate through enteric nervous system, immune vagus nerve, microbiota‐derived‐metabolites including short‐chain fatty acids, bile branched‐chain amino acids. This review summarizes supporting demonstrating alterations bacterial fungal composition that may be associated HD. We focus on mechanisms dysbiosis compromise health, thus triggering neuroinflammatory responses, further highlight outcomes attempts modulate microbiota as therapeutic strategies Ultimately, we discuss dearth data need more longitudinal translational this nascent field. suggest future directions improve our association between microbes pathogenesis other ‘brain body disorders’.

Language: Английский

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Opening the doors of precision medicine: novel tools to assess intestinal barrier in inflammatory bowel disease and colitis-associated neoplasia

Gut, Journal Year: 2024, Volume and Issue: 73(10), P. 1749 - 1762

Published: June 8, 2024

Mounting evidence underscores the pivotal role of intestinal barrier and its convoluted network with diet microbiome in pathogenesis inflammatory bowel disease (IBD) colitis-associated colorectal cancer (CRC). Moreover, bidirectional association liver brain, known as gut-brain axis, plays a crucial developing complications, including extraintestinal manifestations IBD CRC metastasis. Consequently, healing represents therapeutic target these inflammatory-dependent disorders, assessment predicting outcomes, response to therapy manifestations.New advanced technologies are revolutionising our understanding paradigm, enabling accurate aiding unravelling complexity axis. Cutting-edge endoscopic imaging techniques, such ultra-high magnification endocytoscopy probe-based confocal laser endomicroscopy, new allowing real-time exploration 'cellular' barrier. Additionally, novel spatial technology platforms, multispectral imaging, upconversion nanoparticles, digital profiling, optical spectroscopy mass cytometry, enable deep comprehensive 'molecular' 'ultrastructural' In this promising landscape, artificial intelligence standardising integrating tools, thereby contributing prediction outcomes.Looking ahead, integrated approach holds promise uncovering targets, breaking ceiling IBD. Novel molecules, dietary interventions modulation strategies aim restore, reinforce, or modulate These advancements have potential for transformative personalised approaches managing

Language: Английский

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Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 11902 - 11902

Published: July 25, 2023

Central nervous system (CNS) infections including meningitis and encephalitis, resulting from the blood-borne spread of specific microorganisms, provoke tissue damage due to inflammatory process. Moreover, different pathologies such as sepsis can generate systemic inflammation. Bacterial lipopolysaccharide (LPS) induces release mediators molecules, which are then released into bloodstream interact with structures CNS, thus modifying blood–brain barrier’s (BBB´s) blood–cerebrospinal fluid barrier´s (BCSFB´s) function inducing aseptic neuroinflammation. During neuroinflammation, participation glial cells (astrocytes, microglia, oligodendrocytes) plays an important role. They cytokines, chemokines, reactive oxygen species, nitrogen peptides, even excitatory amino acids that lead neuronal damage. The neurons undergo morphological functional changes could initiate alterations neurodegenerative processes. present work aims explain these processes pathophysiological interactions involved in CNS absence microbes or cells.

Language: Английский

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Correlation between Alzheimer’s Disease and Gastrointestinal Tract Disorders

Nutrients, Journal Year: 2024, Volume and Issue: 16(14), P. 2366 - 2366

Published: July 21, 2024

Alzheimer’s disease is the most common cause of dementia globally. The pathogenesis multifactorial and includes deposition amyloid-β in central nervous system, presence intraneuronal neurofibrillary tangles a decreased amount synapses. It remains uncertain what causes progression disease. Nowadays, it suggested that brain connected to gastrointestinal tract, especially enteric system gut microbiome. Studies have found positive association between AD diseases such as periodontitis, Helicobacter pylori infection, inflammatory bowel microbiome disorders. H. its metabolites can enter CNS via oropharyngeal olfactory pathway may predispose onset AD. Periodontitis systemic inflammation low severity with high levels pro-inflammatory cytokines neutrophils. Moreover, lipopolysaccharide from oral bacteria accompanies beta-amyloid plaques form brain. Increased intestinal permeability IBS leads neuronal transference. Chronic lead plaque formation tract spreads vagus nerve. plays an important role many bodily functions, nutrient absorption vitamin production, but also factor development diseases, including Both quantity diversity change significantly patients even people preclinical stage disease, when symptoms are not yet present. influences functioning through, among other things, microbiota–gut–brain axis. Given involvement AD, antibiotic therapy, probiotics prebiotics, faecal transplantation being considered possible therapeutic options.

Language: Английский

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The Gut Microbiota Metabolite Butyrate Modulates Acute Stress-Induced Ferroptosis in the Prefrontal Cortex via the Gut–Brain Axis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1698 - 1698

Published: Feb. 17, 2025

Stress has been implicated in the onset of mental disorders such as depression, with prefrontal cortex (PFC) playing a crucial role. However, underlying mechanisms remain to be fully elucidated. Metabolites secreted by intestinal flora can enter bloodstream and exert regulatory effects on body. Consequently, this study aims investigate molecular which gut influences ferroptosis PFC neurons, thereby affecting depression-like behavioral changes mice subjected acute stress. Initially, we established mouse model restraint stress (3-day duration) verified that stress-induced neurons contributed alterations mice, evidenced morphological, behavioral, biology assessments. Subsequently, through fecal microbiota transplantation (FMT) experiments, significant correlation between stress-exposed mice. 16S rDNA sequencing identified butyric acid-producing bacteria, specifically g_Butyricimonas its primary metabolite, acid, critical regulators acutely stressed Furthermore, intervention butyrate demonstrated potential ameliorate damage blood-brain barriers these This also mitigated behaviors induced alleviating systemic inflammatory responses. The findings indicate plays role Additionally, metabolite modulate gut-brain axis.

Language: Английский

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Exploring the common mechanism of vascular dementia and inflammatory bowel disease: a bioinformatics-based study

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 25, 2024

Emerging evidence has shown that gut diseases can regulate the development and function of immune, metabolic, nervous systems through dynamic bidirectional communication on brain-gut axis. However, specific mechanism intestinal vascular dementia (VD) remains unclear. We designed this study especially, to further clarify connection between VD inflammatory bowel disease (IBD) from bioinformatics analyses. downloaded Gene expression profiles for (GSE122063) IBD (GSE47908, GSE179285) Expression Omnibus (GEO) database. Then individual Set Enrichment Analysis (GSEA) was used confirm two respectively. The common differentially expressed genes (coDEGs) were identified, STRING database together with Cytoscape software construct protein-protein interaction (PPI) network core functional modules. identified hub by using Cytohubba plugin. Ontology (GO) Kyoto Encyclopedia Genes Genomes (KEGG) pathway enrichment analysis applied identify pathways coDEGs genes. Subsequently, receiver operating characteristic (ROC) diagnostic ability these genes, a training dataset verify levels An alternative single-sample gene set (ssGSEA) algorithm analyze immune cell infiltration cells. Finally, correlation cells analyzed. screened 167 coDEGs. main articles focused function. 8 shared including PTPRC, ITGB2, CYBB, IL1B, TLR2, CASP1, IL10RA, BTK. categories mainly involved in regulation neuroinflammatory response. Compared healthy controls, abnormal found IBD. also This suggests may be new risk factor VD. predict complicated Immune-related coDEGS related their association, which requires research prove.

Language: Английский

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C-reactive Protein: An Inflammatory Biomarker and a Predictor of Neurodegenerative Disease in Patients With Inflammatory Bowel Disease?

Cureus, Journal Year: 2024, Volume and Issue: unknown

Published: April 25, 2024

Inflammatory bowel disease (IBD) refers to two chronic conditions of the digestive tract: ulcerative colitis (UC) and Crohn's (CD), representing a progressive inflammatory process that mainly occurs in gut, with frequent extra-intestinal manifestations. Even if remission is periodically obtained for some patients, histological activity symptoms may continue, maintaining persistent systemic inflammation could induce further complications contribute development neurodegenerative disease. C-reactive protein (CRP) an acute-phase reactant widely accepted as dominant serum biomarker IBD. CRP consequently activates complement cascade, supports release pro-inflammatory cytokines, clearance microbial pathogens. All these processes facilitate processes, including atherosclerosis hypercoagulability, alteration intestinal microbiota, increased permeability barrier neurotoxic substances produced by gut microorganisms, due presence high level lipopolysaccharides. For IBD, connection between central nervous system be explained through vagus nerve, carrier CRP, toxic materials brain, potentially inducing vascular lesions damage glial unit, risk degeneration within system. key marker IBD pathogenesis able dissociate into its monomeric form, mCRP, on contact activated cell tissue components via circulation. We hypothesize initiate neuroinflammation neurodegeneration, therefore, investigation significance chronically raised plasma mCRP patients warranted, it represent critical predictive factor associated later risk. Any future initiative aimed at pharmacologic modulation (e.g., blocking CRP-mCRP dissociation), new therapeutic approach protecting against concomitantly reducing neuroinflammation, cognitive decline.

Language: Английский

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Experimental colitis in young Tg2576 mice accelerates the onset of an Alzheimer’s-like clinical phenotype

Alzheimer s Research & Therapy, Journal Year: 2024, Volume and Issue: 16(1)

Published: May 21, 2024

Abstract Systemic inflammation and neuroinflammation affect the natural course of sporadic form Alzheimer’s disease (AD), as supported by epidemiological preclinical data, several studies indicate a higher prevalence AD in patients with inflammatory bowel disease. In this study, we explored whether colitis induced dextran sulfate sodium (DSS) young, presymptomatic/preplaque mice worsens and/or anticipates age-dependent cognitive impairment Tg2576, widely used mouse model AD. We demonstrated that DSS young Tg2576 onset age learning memory deficit Morris water maze test. To explore potential mechanisms behind acceleration decline colitis, focused on gut microbiota, systemic markers. observed Firmicutes/Bacteroidetes ratio change animals comparable to elderly mice, suggesting accelerated microbiota aging not C57BL6 mice. also substantial differences between WT neuroinflammation-related parameters early 3 months age, well before plaque deposition, picture which evolved rapidly (between 5.5 age) contrast littermates treated DSS. detail, following induction exhibited contrasting features expression level inflammation-evoked astrocyte-associated genes hippocampus. No changes microglial occurred hippocampus experimental groups, whereas reduced glial fibrillary acidic protein immunoreactivity was vs. This finding may reflect an atrophic, “loss-of-function” profile, further exacerbated where decreased GFAP mRNA detected. conclusion, suggest as-yet unidentified peripheral mediators evoked involving gut-brain axis emphasize astrocyte profile present leading impaired synaptic morphological functional integrity very sign

Language: Английский

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A Study of Dizziness or Vertigo Cases Associated with Inflammatory Bowel Disease (Crohn’s Disease and Ulcerative Colitis) in a Vertigo Outpatient Clinic

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 341 - 341

Published: Jan. 8, 2025

Background/Objectives: Dizziness and vertigo are reported in about half of patients with inflammatory bowel disease (IBD), including Crohn's (CD) ulcerative colitis (UC). Orthostatic dysregulation (OD) is recognized as one the comorbidities that causes dizziness or IBD. Our hospital affiliated Inflammatory Bowel Disease Center, which specializes diagnosing treating IBD, so cases symptoms associated IBD sometimes referred to our department, a type department rare other facilities. The objective this study evaluate outpatient clinic terms vestibular function OD. Methods: subjects were 221 who from March 2021 September 2024. Results: Of patients, 9 had CD 1 case UC. OD complications significantly more common group than non-IBD group, whereas psychogenic migraine not different between groups, there was no difference dysfunction groups. complication all using ustekinumab. Conclusions: An orthostatic test will be valuable for symptoms.

Language: Английский

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Neuroprotective role of mirabegron: Targeting beta-3 adrenergic receptors to alleviate ulcerative colitis-associated cognitive impairment

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117816 - 117816

Published: Jan. 13, 2025

Language: Английский

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