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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 -
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 -
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 -
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 -
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 -
Frontiers in Cellular and Infection... 2023Alzheimer`s disease (AD) is the most prevalent cause of dementia. It is often assumed that AD is caused by an aggregation of extracellular beta-amyloid and intracellular... (Review)
Review
Alzheimer`s disease (AD) is the most prevalent cause of dementia. It is often assumed that AD is caused by an aggregation of extracellular beta-amyloid and intracellular tau-protein, supported by a recent study showing reduced brain amyloid levels and reduced cognitive decline under treatment with a beta-amyloid-binding antibody. Confirmation of the importance of amyloid as a therapeutic target notwithstanding, the underlying causes of beta-amyloid aggregation in the human brain, however, remain to be elucidated. Multiple lines of evidence point towards an important role of infectious agents and/or inflammatory conditions in the etiology of AD. Various microorganisms have been detected in the cerebrospinal fluid and brains of AD-patients and have thus been hypothesized to be linked to the development of AD, including (PG) and . Intriguingly, these microorganisms are also found in the oral cavity under normal physiological conditions, which is often affected by multiple pathologies like caries or tooth loss in AD patients. Oral cavity pathologies are mostly accompanied by a compositional shift in the community of oral microbiota, mainly affecting commensal microorganisms and referred to as 'dysbiosis'. Oral dysbiosis seems to be at least partly mediated by key pathogens such as PG, and it is associated with a pro-inflammatory state that promotes the destruction of connective tissue in the mouth, possibly enabling the translocation of pathogenic microbiota from the oral cavity to the nervous system. It has therefore been hypothesized that dysbiosis of the oral microbiome may contribute to the development of AD. In this review, we discuss the infectious hypothesis of AD in the light of the oral microbiome and microbiome-host interactions, which may contribute to or even cause the development of AD. We discuss technical challenges relating to the detection of microorganisms in relevant body fluids and approaches for avoiding false-positives, and introduce the antibacterial protein lactoferrin as a potential link between the dysbiotic microbiome and the host inflammatory reaction.
Topics: Host Microbial Interactions; Microbiota; Alzheimer Disease; Humans; Porphyromonas gingivalis; Treponema; Dysbiosis; Mouth; Oral Health; Lactoferrin
PubMed: 37333848
DOI: 10.3389/fcimb.2023.1151021 -
Thoracic Cancer Oct 2023Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk... (Review)
Review
Esophageal squamous cell carcinoma (ESCC) exhibits high incidence with poor prognosis. Alcohol drinking, cigarette smoking, and betel nut chewing are well-known risk factors. Dysbiosis, an imbalance of the microbiota residing in a local environment, is known to be associated with human diseases, especially cancer. This article reviews the current evidence of esophageal microbiota in ESCC carcinogenesis, including initiation, progression, and drug resistance. Articles involving the esophageal microbiota, diagnosis, treatment, and the progression of esophageal cancer were acquired using a comprehensive literature search in PubMed in recent 10 years. Based on 16S rRNA sequencing of human samples, cell, and animal studies, current evidence suggests dysbiosis of the esophagus promotes ESCC progression and chemotherapy resistance, leading to a poor prognosis. Smoking and drinking are associated with esophageal dysbiosis. Specific bacteria have been reported to promote carcinogenesis, involving either progression or drug resistance in ESCC, for example Porphyromonas gingivalis and Fusobacterium nucleatum. These bacteria promote ESCC cell proliferation and migration via the TLR4/NF-κB and IL-6/STAT3 pathways. F. nucleatum induces cisplatin resistance via the enrichment of immunosuppressive myeloid-derived suppressor cells (MDSCs). Correcting the dysbiosis and reducing the abundance of specific esophageal pathogens may help in suppressing cancer progression. In conclusion, esophageal dysbiosis is associated with ESCC progression and chemoresistance. Screening the oral and esophageal microbiota is a potential diagnostic tool for predicting ESCC development or drug-resistance. Repairing esophageal dysbiosis is a novel treatment for ESCC. Clinical trials with probiotics in addition to current chemotherapy are warranted to study the therapeutic effects.
Topics: Animals; Humans; Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Dysbiosis; RNA, Ribosomal, 16S; Carcinogenesis; Microbiota
PubMed: 37675608
DOI: 10.1111/1759-7714.15096 -
Cancers Sep 2023Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral... (Review)
Review
Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral microbiome and immune-inflammatory pathways related to periodontitis may impact the pathophysiology of the gastrointestinal tract and its accessory organs through the so-called "gum-gut axis". In addition to the hematogenous spread of periodontal pathogens and inflammatory cytokines, recent research suggests that oral pathobionts may translocate to the gastrointestinal tract through saliva, possibly impacting neoplastic processes in the gastrointestinal, liver, and pancreatic systems. The exact mechanisms by which oral pathogens contribute to the development of digestive tract cancers are not fully understood but may involve dysbiosis of the gut microbiome, chronic inflammation, and immune modulation/evasion, mainly through the interaction with T-helper and monocytic cells. Specifically, keystone periodontal pathogens, including and , are known to interact with the molecular hallmarks of gastrointestinal cancers, inducing genomic mutations, and promote a permissive immune microenvironment by impairing anti-tumor checkpoints. The evidence gathered here suggests a possible role of periodontitis and oral dysbiosis in the carcinogenesis of the enteral tract. The "gum-gut axis" may therefore represent a promising target for the development of strategies for the prevention and treatment of gastrointestinal cancers.
PubMed: 37760563
DOI: 10.3390/cancers15184594 -
Life Sciences Nov 2023A diverse and stable microbiota promotes a healthy state, nevertheless, an imbalance in gut or oral bacterial composition, called dysbiosis, can cause gastrointestinal... (Review)
Review
A diverse and stable microbiota promotes a healthy state, nevertheless, an imbalance in gut or oral bacterial composition, called dysbiosis, can cause gastrointestinal disorders, systemic inflammatory states and oxidative stress, among others. Recently, gut and oral dysbiosis has been linked to Alzheimer's disease (AD), which is considered the most common form of dementia and a public health priority due to its high prevalence and incidence. The aim of this review is to highlight the implications of gut and oral microbiota in the neuroinflammation characteristic of AD pathology and the subsequent cognitive impairment. It is a systematic review of the current literature obtained by searching the PubMed, Web of Science and Scopus databases. The characteristic intestinal dysbiosis in AD patients leads to increased permeability of the intestinal barrier and activates immune cells in the central nervous system due to translocation of microbiota-derived metabolites and/or bacteria into the circulation leading to increased neuroinflammation and neuronal loss, thus generating the cognitive impairment characteristic of AD. The presence in the central nervous system of Porphyromonas gingivalis can cause an increased neuroinflammation and beta-amyloid peptide accumulation.
Topics: Humans; Alzheimer Disease; Gastrointestinal Microbiome; Neuroinflammatory Diseases; Dysbiosis; Microbiota; Inflammation; Bacteria; Brain
PubMed: 37793482
DOI: 10.1016/j.lfs.2023.122132