Impact of Microbiome–Brain Communication on Neuroinflammation and Neurodegeneration

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14925 - 14925

Published: Oct. 5, 2023

The gut microbiome plays a pivotal role in maintaining human health, with numerous studies demonstrating that alterations microbial compositions can significantly affect the development and progression of various immune-mediated diseases affecting both digestive tract central nervous system (CNS). This complex interplay between microbiota, gut, CNS is referred to as gut-brain axis. microbiota pathogenesis neurodegenerative has gained increasing attention recent years, evidence suggests dysbiosis may contribute disease progression. Clinical have shown composition multiple sclerosis patients, decrease beneficial bacteria an increase pro-inflammatory bacteria. Furthermore, changes within community been linked Parkinson's Alzheimer's disease. Microbiota-gut-brain communication impact through mechanisms, including regulation immune function, production metabolites, well modulation host-derived soluble factors. review describes current literature on axis highlights novel systems allow cross-talk host might influence neuroinflammation neurodegeneration.

Language: Английский

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Hemophore-like proteins of the HmuY family in the oral and gut microbiome: unraveling the mystery of their evolution

Microbiology and Molecular Biology Reviews, Journal Year: 2024, Volume and Issue: 88(1)

Published: Feb. 2, 2024

Heme (iron protoporphyrin IX, FePPIX) is the main source of iron and PPIX for host-associated pathogenic bacteria, including members Bacteroidota (formerly Bacteroidetes) phylum.

Language: Английский

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Alzheimer’s Disease: A Systems View Provides a Unifying Explanation of Its Development

Journal of Alzheimer s Disease, Journal Year: 2022, Volume and Issue: 91(1), P. 43 - 70

Published: Nov. 22, 2022

Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting 50 million people globally. It characterized by the presence of extracellular senile plaques and intracellular neurofibrillary tangles, consisting amyloid-β hyperphosphorylated tau proteins, respectively. Despite global research efforts, there currently no cure available, due in part to an incomplete understanding pathogenesis. Numerous possible mechanisms, or hypotheses, explaining origins sporadic late-onset AD have been proposed, including amyloid-β, inflammatory, vascular, infectious hypotheses. However, despite ample evidence, failure multiple trial drugs at clinical stage illuminates pitfalls these Systems biology strategy which aims elucidate interactions between parts whole. Using this approach, current paper shows how four previously mentioned hypotheses pathogenesis can be intricately connected. This approach allows for seemingly contradictory evidence unified system-focused explanation development. Within view, it seen that agents, such as P. gingivalis, may play central role. The data presented here when present, gingivalis its virulence factors, gingipains, induce exacerbate pathologies underlying AD. supports view specifically suitable treatment targets

Language: Английский

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Proteome and immune responses of extracellular vesicles derived from macrophages infected with the periodontal pathogen Tannerella forsythia

Journal of Extracellular Vesicles, Journal Year: 2023, Volume and Issue: 12(12)

Published: Nov. 28, 2023

Periodontitis is a chronic inflammatory disease caused by periodontal pathogens in subgingival plaque and associated with systemic diseases. Extracellular vesicles (EVs) released from host cells carry variety of biological molecules are interest for their role progression as diagnostic markers. In the present study, we analysed proteome response EVs derived macrophages infected Tannerella forsythia, pathogen. The isolated cell conditioned medium T. forsythia-infected were divided into two distinct vesicles, macrophage-derived forsythia-derived OMVs, size exclusion chromatography combined density gradient ultracentrifugation. Proteome analysis showed that forsythia infection, enriched pro-inflammatory cytokines mediators periodontitis progression. OMVs harboured several known virulence factors, including BspA, sialidase, GroEL various bacterial lipoproteins. induced responses via TLR2 activation. addition, demonstrated actively when encountered soluble molecules. Taken together, our results provide insight characterisation

Language: Английский

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Periodontitis and Alzheimer’s Disease: Is There a Connection?

Oral, Journal Year: 2024, Volume and Issue: 4(1), P. 61 - 73

Published: Jan. 22, 2024

The oral health/systemic health connection has been an area of research interest that increased dramatically during the 1990s. Periodontal disease associated with a number systemic conditions, including cardiovascular disease, diabetes, pre-term low-birth-weight infants, respiratory rheumatoid arthritis, cancer, and Alzheimer’s disease. Inflammation is obvious link connects periodontal these but this association casual or causal? We will address biologic plausibility, evidence from human studies, animal therapeutic interventions as we review current understanding between periodontitis

Language: Английский

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Oral Microbially-Induced Small Extracellular Vesicles Cross the Blood–Brain Barrier

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4509 - 4509

Published: April 20, 2024

Porphyromonas gingivalis (Pg) and its gingipain proteases contribute to Alzheimer's disease (AD) pathogenesis through yet unclear mechanisms. Cellular secretion of small extracellular vesicles or exosomes (EXO) increases with aging as part the senescence-associated secretory phenotype (SASP). We have shown that EXO isolated from Pg-infected dendritic cells contain gingipains other Pg antigens transmit senescence bystander gingival cells, inducing alveolar bone loss in mice vivo. Here, were gingiva humans with/without periodontitis (PD) determine their ability penetrate blood-brain barrier (BBB) vitro PD was induced by oral gavage for 6 weeks C57B6 mice. brain donor (PD EXO) control animals (Con characterized NTA, Western blot, TEM. Gingival Con labeled injected into uninfected WT mouse model. biodistribution brains tracked an vivo imaging system (IVIS) confocal microscopy. The effect human on BBB integrity permeability examined using TEER FITC dextran assays a 3D model BBB. (RGP Mfa-1) detected derived tissues Orally penetrated recipient colocalized hippocampal microglial cells. IL-1β IL-6 expressed not EXO. Human promoted vitro. This is first demonstration microbial-induced cavity can disseminate, cross BBB, may AD pathogenesis.

Language: Английский

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Exploring the Link Between Periodontitis and Alzheimer’s Disease—Could a Nanoparticulate Vaccine Break It?

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(2), P. 141 - 141

Published: Jan. 21, 2025

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder, as approximately 55 million people worldwide are affected, with a significant tendency to increase. It reveals three main pathological features: amyloid plaques, neurofibrillary tangles, and neuroinflammation, responsible for changes that slowly lead deterioration of personality cognitive control. Over century after first case report, effective treatments remain elusive, likely due an incomplete understanding precise mechanisms driving its pathogenesis. Recent studies provide growing evidence infectious aetiology AD, hypothesis reinforced by findings beta functions antimicrobial peptide. Among microorganisms already associated Porphyromonas gingivalis (Pg), keystone pathogen periodontitis (PeD), has received particular attention possible aetiological agent AD development. Herein, we review epidemiological genetic linking PeD Pg highlighting identification periodontal bacteria in post mortem analysis patients’ brains identifying putative mechanistic links relevant biological plausibility association. With focus on research shifting from cure prevention, proposed open door unravelling new prophylactic approaches able reduce global burden AD. As hypothesised this review, these could include bionanotechnological approach involving development oral nanoparticulate vaccine based Pg-specific antigens. Such prevent antigens progressing brain triggering pathology, representing promising step toward innovative prevention.

Language: Английский

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Oral microbiota and central nervous system diseases: A review

Neuroprotection/Neuroprotection (Chichester, England. Print), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Abstract Oral microbiota is the second largest microbial colony in body and forms a complex ecological community that influences oral brain health. Impaired homeostasis of can lead to pathological changes, resulting central nervous system (CNS) diseases. However, mechanisms clinical value how microbiome remain unclear. This review summarizes recent findings on role CNS diseases proposes potential approaches understand way communicate. We propose three underlying patterns involving neuroinflammation, neuroendocrine regulation, signaling between also summarize characteristics utilization ischemic stroke, Alzheimer's Parkinson's disease, intracranial aneurysms, mental disorders. Although current are preliminary evidence incomplete, biomarker for diagnosis treatment

Language: Английский

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Porphyromonas gingivalis and Its Outer Membrane Vesicles Induce Neuroinflammation in Mice Through Distinct Mechanisms

Immunity Inflammation and Disease, Journal Year: 2025, Volume and Issue: 13(2)

Published: Feb. 1, 2025

ABSTRACT Background Alzheimer's disease (AD) is the most common chronic neurodegenerative disorder, with neuroinflammation playing an important role in its progression to become a major research focus. The of Porphyromonas gingivalis ( Pg ) and outer membrane vesicles OMVs) AD development uncertain, particularly regarding their effects on neuroinflammation. Methods cognition mice injected , OMVs, or PBS via tail vein was assessed by Morris water maze test. Pathological changes mouse brain were analyzed immunohistochemistry, immunofluorescence hematoxylin‒eosin (H&E) staining, ultrastructure hippocampus observed transmission electron microscopy (TEM). Plasma levels inflammatory factors enzyme‐linked immunosorbent assay (ELISA). Protein factor, occludin, NLRP3 inflammasome‐related proteins western blotting. Results Memory impairment; notable neuroinflammation, including astrocyte microglial activation; elevated protein IL‐1β, TNF‐α, IL‐6 detected OMV groups. However, induced weight loss systemic inflammation, such as splenomegaly increased IL‐1β TNF‐α plasma, whereas OMVs had minimal impact. In addition, more pronounced activation inflammasome compared OMVs. contrast, only group exhibited blood−brain barrier (BBB) disruption characterized reduced integrity tight junctions lower occludin protein. Conclusions associated significant immune response which turn exacerbates activating inflammasome. might elude disrupt junctions, thereby entering directly triggering

Language: Английский

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Oral Health Status and Factors Associated with Oral Health in Patients with Alzheimer’s Disease: A Matched Case-Control Observational Study

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(5), P. 1412 - 1412

Published: Feb. 20, 2025

Background: Alzheimer’s disease (AD) is a chronic neurodegenerative disease, ranking as the seventh leading cause of death in both sexes. There increasing awareness role periodontal and severe tooth loss modifiable risk factor for developing AD. The aim present observational study was to assess AD patients with non-affected healthy controls context their dental health outcomes; additionally, potential impact anamnestic factors lifestyle habits on oral outcomes also studied. Methods: A total n = 41 receiving treatment at Department Psychiatry, University Szeged, were compared age- gender-matched from individuals seeking retirement homes (mean age 83.32 ± 7.82 years). Dental status indices assessed according World Health Organization (WHO) criteria. Results: Overall, 51.2%, 68.3%, 87.8% received mood stabilizers, drugs non-cognitive symptoms cognitive symptoms, respectively. Severe observed 43.9% 56.1% controls, no significant differences among regarding studied (p > 0.05 all indicators). had significantly higher plaque (%) (59.06 15.45 vs. 41.35 7.97; p < 0.001), bleeding probing (BOP%) (62.65 12.00 40.12 10.86; pocket depth [PD] (2.63 0.56 2.29 0.13; 0.002) attachment [AL] (2.85 0.79 2.39 0.41; 0.026) values, controls. Smoking (vs. non-smokers; 56.28 12.36 51.40 13.23, 0.038) consumption alcohol non-drinkers; 58.68 9.86 54.78 14.86, 0.040) associated [%], while similar effects shown parameters 0.05). In contrast, coffee intake vitamin supplement use effect or cases). Conclusions: results our underscore substantial needs patients, calling heightened healthcare professionals.

Language: Английский

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