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Inflammatory Bowel Diseases Jul 2023One of the prospective sequelae of periodontal disease (PD), chronic inflammation of the oral mucosa, is the development of inflammatory gastrointestinal (GI) disorders... (Review)
Review
One of the prospective sequelae of periodontal disease (PD), chronic inflammation of the oral mucosa, is the development of inflammatory gastrointestinal (GI) disorders due to the amplification and expansion of the oral pathobionts. In addition, chronic inflammatory diseases related to the GI tract, which include inflammatory bowel disease (IBD), can lead to malignancy susceptibility in the colon of both animals and humans. Recent studies suggest that dysbiosis of the oral microbiota can alter the microbial composition in relative abundance or diversity of the distal gut, leading to the progression of digestive carcinogenesis. The link between PD and specific GI disorders is also closely associated with the migration and colonization of periodontal pathogens and the subsequent microbe-reactive T cell induction within the intestines. In this review, an in-depth examination of this relationship and the accessibility of different mouse models of IBD and PD may shed light on the current dogma. As such, oral microbiota dysbiosis involving specific bacteria, including Fusobacterium nucleatum and Porphyromonas gingivalis, can ultimately lead to gut malignancies. Further understanding the precise mechanism(s) of the oral-gut microbial axis in PD, IBD, and colorectal cancer pathogenesis will be pivotal in diagnosis, prognosis, and future treatment.
Topics: Animals; Mice; Humans; Dysbiosis; Prospective Studies; Periodontal Diseases; Gastrointestinal Diseases; Inflammatory Bowel Diseases; Porphyromonas gingivalis
PubMed: 36527679
DOI: 10.1093/ibd/izac241 -
Journal of Advanced Research Dec 2023Porphyromonas gingivalis (PG)-infected periodontitis is in close connection with the development of Alzheimer's disease (AD). PG-derived extracellular vesicles (pEVs)...
INTRODUCTION
Porphyromonas gingivalis (PG)-infected periodontitis is in close connection with the development of Alzheimer's disease (AD). PG-derived extracellular vesicles (pEVs) contain inflammation-inducing virulence factors, including gingipains (GPs) and lipopolysaccharide (LPS).
OBJECTIVES
To understand how PG could cause cognitive decline, we investigated the effects of PG and pEVs on the etiology of periodontitis and cognitive impairment in mice.
METHODS
Cognitive behaviors were measured in the Y-maze and novel object recognition tasks. Biomarkers were measured using ELISA, qPCR, immunofluorescence assay, and pyrosequencing.
RESULTS
pEVs contained neurotoxic GPs and inflammation-inducible fimbria protein and LPS. Gingivally exposed, but not orally gavaged, PG or pEVs caused periodontitis and induced memory impairment-like behaviors. Gingival exposure to PG or pEVs increased TNF-α expression in the periodontal and hippocampus tissues. They also increased hippocampal GPIba1, LPSIba1, and NF-κBIba1 cell numbers. Gingivally exposed PG or pEVs decreased BDNF, claudin-5, and N-methyl-D-aspartate receptor expression and BDNFNeuN cell number. Gingivally exposed fluorescein-5-isothiocyanate-labeled pEVs (F-pEVs) were detected in the trigeminal ganglia and hippocampus. However, right trigeminal neurectomy inhibited the translocation of gingivally injected F-EVs into the right trigeminal ganglia. Gingivally exposed PG or pEVs increased blood LPS and TNF-α levels. Furthermore, they caused colitis and gut dysbiosis.
CONCLUSION
Gingivally infected PG, particularly pEVs, may cause cognitive decline with periodontitis. PG products pEVs and LPS may be translocated into the brain through the trigeminal nerve and periodontal blood pathways, respectively, resulting in the cognitive decline, which may cause colitis and gut dysbiosis. Therefore, pEVs may be a remarkable risk factor for dementia.
Topics: Mice; Animals; Porphyromonas gingivalis; Lipopolysaccharides; Dysbiosis; Tumor Necrosis Factor-alpha; Brain-Derived Neurotrophic Factor; Periodontitis; Inflammation; Trigeminal Nerve; Colitis; Cognitive Dysfunction
PubMed: 36796586
DOI: 10.1016/j.jare.2023.02.006 -
Pathogens (Basel, Switzerland) Sep 2023Several types of phototherapy target human pathogens and () in particular. The various approaches can be organized into five different treatment modes sorted by... (Review)
Review
Several types of phototherapy target human pathogens and () in particular. The various approaches can be organized into five different treatment modes sorted by different power densities, interaction times, effective wavelengths and mechanisms of action. Mode 1: antimicrobial ultraviolet (aUV); mode 2: antimicrobial blue light (aBL); mode 3: antimicrobial selective photothermolysis (aSP); mode 4: antimicrobial vaporization; mode 5: antimicrobial photodynamic therapy (aPDT). This report reviews the literature to identify for each mode (a) the putative molecular mechanism of action; (b) the effective wavelength range and penetration depth; (c) selectivity; (d) in vitro outcomes; and (e) clinical trial/study outcomes as these elements apply to (). The characteristics of each mode influence how each is translated into the clinic.
PubMed: 37764967
DOI: 10.3390/pathogens12091160 -
International Journal of Molecular... Aug 2023Atherosclerosis (AS) is an inflammatory vascular disease that constitutes a major underlying cause of cardiovascular diseases (CVD) and stroke. Infection is a... (Review)
Review
Atherosclerosis (AS) is an inflammatory vascular disease that constitutes a major underlying cause of cardiovascular diseases (CVD) and stroke. Infection is a contributing risk factor for AS. Epidemiological evidence has implicated individuals afflicted by periodontitis displaying an increased susceptibility to AS and CVD. This review concisely outlines several prevalent periodontal pathogens identified within atherosclerotic plaques, including , , and . We review the existing epidemiological evidence elucidating the association between these pathogens and AS-related diseases, and the diverse mechanisms for which these pathogens may engage in AS, such as endothelial barrier disruption, immune system activation, facilitation of monocyte adhesion and aggregation, and promotion of foam cell formation, all of which contribute to the progression and destabilization of atherosclerotic plaques. Notably, the intricate interplay among bacteria underscores the complex impact of periodontitis on AS. In conclusion, advancing our understanding of the relationship between periodontal pathogens and AS will undoubtedly offer invaluable insights and potential therapeutic avenues for the prevention and management of AS.
Topics: Humans; Plaque, Atherosclerotic; Atherosclerosis; Fusobacterium nucleatum; Cardiovascular Diseases; Porphyromonas gingivalis
PubMed: 37629042
DOI: 10.3390/ijms241612861 -
Nature Communications Feb 2024Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the...
Periodontitis is closely related to inflammatory bowel disease (IBD). An excessive and non-self-limiting immune response to the dysbiotic microbiome characterizes the two. However, the underlying mechanisms that overlap still need to be clarified. We demonstrate that the critical periodontal pathogen Porphyromonas gingivalis (Pg) aggravates intestinal inflammation and Th17/Treg cell imbalance in a gut microbiota-dependent manner. Specifically, metagenomic and metabolomic analyses shows that oral administration of Pg increases levels of the Bacteroides phylum but decreases levels of the Firmicutes, Verrucomicrobia, and Actinobacteria phyla. Nevertheless, it suppresses the linoleic acid (LA) pathway in the gut microbiota, which was the target metabolite that determines the degree of inflammation and functions as an aryl hydrocarbon receptor (AHR) ligand to suppress Th17 differentiation while promoting Treg cell differentiation via the phosphorylation of Stat1 at Ser727. Therapeutically restoring LA levels in colitis mice challenged with Pg exerts anti-colitis effects by decreasing the Th17/Treg cell ratio in an AHR-dependent manner. Our study suggests that Pg aggravates colitis via a gut microbiota-LA metabolism-Th17/Treg cell balance axis, providing a potential therapeutically modifiable target for IBD patients with periodontitis.
Topics: Humans; Mice; Animals; T-Lymphocytes, Regulatory; Porphyromonas gingivalis; Gastrointestinal Microbiome; Linoleic Acid; Mice, Inbred C57BL; Colitis; Inflammatory Bowel Diseases; Periodontitis; Inflammation; Th17 Cells
PubMed: 38388542
DOI: 10.1038/s41467-024-45473-y -
Pathogens (Basel, Switzerland) Aug 2023The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both... (Review)
Review
The intricate interplay between oral microbiota and the human host extends beyond the confines of the oral cavity, profoundly impacting the general health status. Both periodontal diseases and respiratory diseases show high prevalence worldwide and have a marked influence on the quality of life for the patients. Accumulating studies are establishing a compelling association between periodontal diseases and respiratory diseases. Here, in this review, we specifically focus on the key periodontal pathogenic bacteria and and dissect their roles in the onset and course of respiratory diseases, mainly pneumonia, chronic obstructive pulmonary disease, lung cancer, and asthma. The mechanistic underpinnings and molecular processes on how and contribute to the progression of related respiratory diseases are further summarized and analyzed, including: induction of mucus hypersecretion and chronic airway inflammation; cytotoxic effects to disrupt the morphology and function of respiratory epithelial cells; synergistic pathogenic effects with respiratory pathogens like and . By delving into the complex relationship to periodontal diseases and periodontopathogens, this review helps unearth novel insights into the etiopathogenesis of respiratory diseases and inspires the development of potential therapeutic avenues and preventive strategies.
PubMed: 37764918
DOI: 10.3390/pathogens12091110 -
Journal of Dental Research Jul 2023Growing evidence demonstrates the relationship between periodontitis and atherosclerotic cardiovascular diseases. The periodontal pathogen (Pg) has been shown to...
Growing evidence demonstrates the relationship between periodontitis and atherosclerotic cardiovascular diseases. The periodontal pathogen (Pg) has been shown to contribute to the progression of atherosclerosis. Cyclic diadenylate monophosphate (c-di-AMP) has been widely studied as an immune adjuvant for tumor immunotherapy, given its ability to activate the stimulator of interferon genes (STING) and regulate trained immunity. This study sought to elucidate the role of c-di-AMP in Pg-associated atherosclerosis. Periodontitis and atherosclerosis mouse models were established by ligature application around maxillary second molars and feeding knockout mice with a high-fat diet. We found that periodontitis and atherosclerosis were more severe in mice exposed to Pg than mice that underwent ligature placement only, while prophylactic treatment with c-di-AMP activated trained immunity and elicited significant alleviation of alveolar bone resorption, as well as reduced blood lipid levels and atherosclerotic plaque accumulation. After 3 mo of intervention, c-di-AMP limited the elevation of cytokines interleukin (IL)-6, IL-1β, tumor necrosis factor α, and interferon β; extracellular matrix remodeling enzymes MMP-2 and MMP-9; and adhesion molecules ICAM-1 and VCAM-1 gene expression. The mechanism underlying Pg-aggravated atherosclerosis may be attributed to changes in microbiota composition in oral and aortic plaques and excess inflammatory response, whereas c-di-AMP could prevent the effects of Pg infection due to its potential ability to activate trained immunity and regulate microecological balance. Our findings suggest a positive role of c-di-AMP in alleviating Pg-aggravated atherosclerosis by regulating the immune response and influencing the local microenvironment.
Topics: Animals; Mice; Porphyromonas gingivalis; Atherosclerosis; Periodontitis; Interleukin-6; Alveolar Bone Loss; Adenosine Monophosphate
PubMed: 37029659
DOI: 10.1177/00220345231162344 -
The Japanese Dental Science Review Dec 2023Patients with neurological diseases, such as schizophrenia, tend to show low K-Cl co-transporter 2 (KCC2) levels in the brain. The cause of these diseases has been... (Review)
Review
Patients with neurological diseases, such as schizophrenia, tend to show low K-Cl co-transporter 2 (KCC2) levels in the brain. The cause of these diseases has been associated with stress and neuroinflammation. However, since the pathogenesis of these diseases is not yet fully investigated, drug therapy is still limited to symptomatic therapy. Targeting KCC2, which is mainly expressed in the brain, seems to be an appropriate approach in the treatment of these diseases. In this review, we aimed to discuss about stress and inflammation, KCC2 and Gamma-aminobutyric acid (GABA) function, diseases which decrease the KCC2 levels in the brain, factors that regulate KCC2 activity, and the possibility to overcome neuronal dysfunction targeting KCC2. We also aimed to discuss the relationships between neurological diseases and LPS caused by (), which is a type of oral bacterium. Clinical trials on oxytocin, sirtuin 1 (SIRT1) activator, and transient receptor potential cation channel subfamily V Member 1 activator have been conducted to develop effective treatment methods. We believe that KCC2 modulators that regulate mitochondria, such as oxytocin, glycogen synthase kinase 3β (GSK3β), and SIRT1, can be potential targets for neurological diseases.
PubMed: 38022385
DOI: 10.1016/j.jdsr.2023.11.001 -
International Endodontic Journal Oct 2023Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is...
AIM
Angiogenesis contributes to the development of apical periodontitis, periodontitis, and other oral pathologies; however, it remains unclear how this process is triggered. The aim was to evaluate whether lipopolysaccharide (LPS) from Porphyromonas endodontalis and Porphyromonas gingivalis induced angiogenesis-related effects in vitro via TLR2 and TLR4.
METHODOLOGY
Porphyromonas endodontalis LPS (ATCC 35406 and clinical isolate) was purified with TRIzol, whereas P. gingivalis LPS was obtained commercially. The effects of the different LPS (24 h) in endothelial cell migration were analysed by Transwell assays, following quantification in an optical microscope (40×). The effects of LPS on FAK Y397 phosphorylation were assessed by Western blotting. Angiogenesis in vitro was determined in an endothelial tube formation assay (14 h) in Matrigel in the absence or presence of either LPS. IL-6 and VEGF-A levels were determined in cell supernatants, following 24 h treatment with LPS, and measured in multiplex bead immunoassay. The involvement of TLR2 and TLR4 was assessed with blocking antibodies. The statistical analysis was performed using STATA 12® (StataCorp LP).
RESULTS
The results revealed that P. endodontalis LPS, but not P. gingivalis LPS, stimulated endothelial cell migration. Pre-treatment with anti-TLR2 and anti-TLR4 antibodies prevented P. endodontalis LPS-induced cell migration. P. endodontalis LPS promoted FAK phosphorylation on Y397, as observed by an increased p-FAK/FAK ratio. Both P. gingivalis and P. endodontalis LPS (ATCC 35406) induced endothelial tube formation in a TLR-2 and -4-dependent manner, as shown by using blocking antibodies, however, only TLR2 blocking decreased tube formation induced by P. endodontalis (clinical isolate). Moreover, all LPS induced IL-6 and VEGF-A synthesis in endothelial cells. TLR2 and TLR4 were required for IL-6 induction by P. endodontalis LPS (ATCC 35406), while only TLR4 was involved in IL-6 secretion by the other LPS. Finally, VEGF-A synthesis did not require TLR signalling.
CONCLUSION
Porphyromonas endodontalis and P. gingivalis LPS induced angiogenesis via TLR2 and TLR4. Collectively, these data contribute to understanding the role of LPS from Porphyromonas spp. in angiogenesis and TLR involvement.
Topics: Lipopolysaccharides; Toll-Like Receptor 2; Porphyromonas gingivalis; Porphyromonas endodontalis; Vascular Endothelial Growth Factor A; Endothelial Cells; Antibodies, Blocking; Interleukin-6; Toll-Like Receptor 4
PubMed: 37461231
DOI: 10.1111/iej.13957