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Microorganisms Jul 2023Pathogens that play a role in the development and progression of periodontitis have gained significant attention due to their implications in the onset of various... (Review)
Review
Pathogens that play a role in the development and progression of periodontitis have gained significant attention due to their implications in the onset of various systemic diseases. Periodontitis is characterized as an inflammatory disease of the gingival tissue that is mainly caused by bacterial pathogens. Among them, , , , , and are regarded as the main periodontal pathogens. These pathogens elicit the release of cytokines, which in combination with their virulence factors induce chronic systemic inflammation and subsequently impact neural function while also altering the permeability of the blood-brain barrier. The primary objective of this review is to summarize the existing information regarding periodontal pathogens, their virulence factors, and their potential association with neuroinflammation and neurodegenerative diseases. We systematically reviewed longitudinal studies that investigated the association between periodontal disease and the onset of neurodegenerative disorders. Out of the 24 studies examined, 20 showed some degree of positive correlation between periodontal disease and neurodegenerative disorders, with studies focusing on cognitive function demonstrating the most robust effects. Therefore, periodontal pathogens might represent an exciting new approach to develop novel preventive treatments for neurodegenerative diseases.
PubMed: 37513004
DOI: 10.3390/microorganisms11071832 -
Molecular Oral Microbiology Mar 2024The oral cavity harbors a diverse and dynamic bacterial biofilm community which is pivotal to oral health maintenance and, if turning dysbiotic, can contribute to... (Review)
Review
The oral cavity harbors a diverse and dynamic bacterial biofilm community which is pivotal to oral health maintenance and, if turning dysbiotic, can contribute to various diseases. Glycans as unsurpassed carriers of biological information are participating in underlying processes that shape oral health and disease. Bacterial glycoinfrastructure-encompassing compounds as diverse as glycoproteins, lipopolysaccharides (LPSs), cell wall glycopolymers, and exopolysaccharides-is well known to influence bacterial fitness, with direct effects on bacterial physiology, immunogenicity, lifestyle, and interaction and colonization capabilities. Thus, understanding oral bacterias' glycoinfrastructure and encoded glycolanguage is key to elucidating their pathogenicity mechanisms and developing targeted strategies for therapeutic intervention. Driven by their known immunological role, most research in oral glycobiology has been directed onto LPSs, whereas, recently, glycoproteins have been gaining increased interest. This review draws a multifaceted picture of the glycolanguage, with a focus on glycoproteins, manifested in prominent oral bacteria, such as streptococci, Porphyromonas gingivalis, Tannerella forsythia, and Fusobacterium nucleatum. We first define the characteristics of the different glycoconjugate classes and then summarize the current status of knowledge of the structural diversity of glycoconjugates produced by oral bacteria, describe governing biosynthetic pathways, and list biological roles of these energetically costly compounds. Additionally, we highlight emerging research on the unraveling impact of oral glycoinfrastructure on dental caries, periodontitis, and systemic conditions. By integrating current knowledge and identifying knowledge gaps, this review underscores the importance of studying the glycolanguage oral bacteria speak to advance our understanding of oral microbiology and develop novel antimicrobials.
PubMed: 38515284
DOI: 10.1111/omi.12456 -
Clinical & Translational Oncology :... Oct 2023Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related... (Review)
Review
Periodontitis is a polymicrobial disorder caused by dysbiosis. Porphyromonas gingivalis (P.gingivalis) and Fusobacterium nucleatum (F.nucleatum) are pathobiont related to periodontitis pathogenesis and were found to be abundant in the intestinal mucosa of inflammatory bowel disease (IBD) and colorectal cancer (CRC) patients. Besides, periodontal infections have been found in a variety of tissues and organs, indicating that periodontitis is not just an inflammation limited to the oral cavity. Considering the possible translocation of pathobiont from the oral cavity to the gastrointestinal (GI) tract, this study aimed to review the published articles in this field to provide a comprehensive view of the existing knowledge about the relationship between periodontitis and GI malignancies by focusing on the oral/gut axis.
Topics: Humans; Periodontitis; Porphyromonas gingivalis; Inflammation; Gastrointestinal Neoplasms
PubMed: 37036595
DOI: 10.1007/s12094-023-03162-0 -
Journal of Clinical Periodontology Nov 2023The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative...
AIM
The link between periodontitis and intestinal dysbiosis, two factors that contribute to atherosclerosis, has not been clearly defined. We investigated the integrative effects of oral infection with Porphyromonas gingivalis (PG), the major pathogen for periodontitis, on intestinal microbiota and atherosclerosis.
MATERIALS AND METHODS
ApoE mice were fed a normal chow diet (NC), a Western diet (WD) or a WD with oral PG infection (PG). The PG infection was investigated by placing a total of 10 CFUs of live PG into the oral cavity of each mouse using a feeding needle five times a week for 3 weeks. Atherosclerotic lesions of the aortae were measured, and blood lipoproteins and the expression of molecules related to lipid metabolism in the liver were analysed. We also performed 16S RNA sequencing and a microbiome analysis using faeces.
RESULTS
En face bloc preparation of the aortae showed that the PG group had a 1.7-fold increase in atherosclerotic lesions compared with the WD group (p < .01). Serum analyses showed that oral PG infection induced a significant decrease in high-density lipoprotein (HDL) and triglyceride. Western blots of hepatic tissue lysates revealed that PG infection reduced the expression of scavenger receptor class B type 1 (SR-B1) in the liver by 50%. Faecal microbiota analysis revealed that species richness estimates (Chao1, ACE) decreased immediately after PG infection. PG infection also induced a significant decrease in Shannon diversity and an increase in Simpson's indices in the WD-fed mice. PG infection significantly increased the phyla Actinobacteria and Deferribacteres, along with the species Mucispirillum schaedleri and Lactobacillus gasseri, in the mice. The functional study showed that PG infection increased the expression of proteins that function in carbohydrate and glucose metabolism, including phosphotransferase system (PTS) proteins and the GntR family transcriptional regulator.
CONCLUSIONS
Oral PG infection promotes atherosclerosis and induces significant metabolic changes, including reduced serum HDL and reduced hepatic SR-B1 and ABCA1 expression, as well as changes in intestinal microbiota. Our study suggests that intestinal dysbiosis accompanies periodontitis and could play a role in atherosclerosis.
Topics: Mice; Animals; Porphyromonas gingivalis; Gastrointestinal Microbiome; Dysbiosis; Atherosclerosis; Periodontitis
PubMed: 37621247
DOI: 10.1111/jcpe.13864 -
Microorganisms Aug 2023Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community... (Review)
Review
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the . Twenty-four studies were eligible. We identified strong evidence of two microbial markers and for ADA vs. CRC, and nine microbial markers -Lachnoclostridium, -Ruminococcus, spp., , Enterobacteriaceae, spp., Bacteroides, -, spp.-, , and for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
PubMed: 37630597
DOI: 10.3390/microorganisms11082037 -
Clinical Oral Implants Research Nov 2023To answer the following PECO question: "In systemically healthy human subjects (P), which are the differences between peri-implantitis (E) and peri-implant... (Meta-Analysis)
Meta-Analysis Review
AIM
To answer the following PECO question: "In systemically healthy human subjects (P), which are the differences between peri-implantitis (E) and peri-implant health/mucositis (C) in terms of bacterial presence/count (O)?"
MATERIALS AND METHODS
Cross-sectional studies fulfilling specific inclusion criteria established to answer the PECO question were included. Two review authors independently searched for studies, screened the titles and abstracts, did full-text analysis, extracted the data from the included reports, and performed the risk of bias assessment through an adaptation of the Newcastle/Ottawa tool for cross-sectional studies and of the JBI critical appraisal checklist. In case of disagreement, a third reviewer author took the final decision. Study results were summarized using random effects meta-analyses.
RESULTS
A total of 12 studies were included, involving 1233 participants and 1513 implants. Peri-implantitis was associated with the presence of S. epidermidis (Odds ratio, OR = 10.28 [95% Confidence interval, CI: 1.26-83.98]), F. nucleatum (OR = 7.83 [95% CI: 2.24-27.36]), T. denticola (OR = 6.11 [95% CI: 2.72-13.76]), T. forsythia (OR = 4.25 [95% CI: 1.71-10.57]), P. intermedia (OR = 3.79 [95% CI: 1.07-13.35]), and P. gingivalis (OR = 2.46 [95% CI: 1.21-5.00]). Conversely, the presence of A. actinomycetemcomitans (OR = 3.82 [95% CI: 0.59-24.68]), S. aureus (OR = 1.05 [95% CI: 0.06-17.08]), and C. rectus (OR = 1.48 [95% CI: 0.69-3.17]) was not associated with peri-implantitis.
CONCLUSIONS
Peri-implantitis is associated with the presence of S. epidermidis and specific periodontopathogens (P. gingivalis, T. forsythia, T. denticola, F. nucleatum, and P. intermedia). (CRD42021254589).
Topics: Humans; Peri-Implantitis; Staphylococcus aureus; Cross-Sectional Studies; Porphyromonas gingivalis; Microbiota; Dental Implants
PubMed: 37523470
DOI: 10.1111/clr.14153 -
Inflammation May 2024The periodontium is a highly organized ecosystem, and the imbalance between oral microorganisms and host defense leads to periodontal diseases. The periodontal... (Review)
Review
The periodontium is a highly organized ecosystem, and the imbalance between oral microorganisms and host defense leads to periodontal diseases. The periodontal pathogens, mainly Gram-negative anaerobic bacteria, colonize the periodontal niches or enter the blood circulation, resulting in periodontal tissue destruction and distal organ damage. This phenomenon links periodontitis with various systemic conditions, including cardiovascular diseases, malignant tumors, steatohepatitis, and Alzheimer's disease. Autophagy is an evolutionarily conserved cellular self-degradation process essential for eliminating internalized pathogens. Nowadays, increasing studies have been carried out in cells derived from periodontal tissues, immune system, and distant organs to investigate the relationship between periodontal pathogen infection and autophagy-related activities. On one hand, as a vital part of innate and adaptive immunity, autophagy actively participates in host resistance to periodontal bacterial infection. On the other, certain periodontal pathogens exploit autophagic vesicles or pathways to evade immune surveillance, therefore achieving survival within host cells. This review provides an overview of the autophagy process and focuses on periodontopathogen-related autophagy and their involvements in cells of different tissue origins, so as to comprehensively understand the role of autophagy in the occurrence and development of periodontal diseases and various periodontitis-associated systemic illnesses.
PubMed: 38762837
DOI: 10.1007/s10753-024-02049-8 -
Critical Reviews in Microbiology Mar 2024The cause of Alzheimer's disease (AD), and the pathophysiological mechanisms involved, remain major unanswered questions in medical science. Oral bacteria, especially...
The cause of Alzheimer's disease (AD), and the pathophysiological mechanisms involved, remain major unanswered questions in medical science. Oral bacteria, especially those species associated with chronic periodontitis and particularly , are being linked causally to AD pathophysiology in a subpopulation of susceptible individuals. produces large amounts of proteolytic enzymes, haem and iron capture proteins, adhesins and internalins that are secreted and attached to the cell surface and concentrated onto outer membrane vesicles (OMVs). These enzymes and adhesive proteins have been shown to cause host tissue damage and stimulate inflammatory responses. The ecological and pathophysiological roles of OMVs, their ability to disperse widely throughout the host and deliver functional proteins lead to the proposal that they may be the link between a focal infection in the subgingivae during periodontitis and neurodegeneration in AD. OMVs can cross the blood brain barrier and may accelerate AD-specific neuropathology by increasing neuroinflammation, plaque/tangle formation and dysregulation of iron homeostasis, thereby inducing ferroptosis leading to neuronal death and neurodegeneration.
Topics: Humans; Porphyromonas gingivalis; Alzheimer Disease; Adhesins, Bacterial; Periodontitis; Iron
PubMed: 36597758
DOI: 10.1080/1040841X.2022.2163613 -
Microbiology Spectrum Aug 2023Bacteria have to persist under low iron conditions in order to adapt to the nutritional immunity of a host. Since the knowledge of iron stimulon of is sparse, we...
Bacteria have to persist under low iron conditions in order to adapt to the nutritional immunity of a host. Since the knowledge of iron stimulon of is sparse, we examined oral (Porphyromonas gingivalis and Prevotella intermedia) and gut (Bacteroides thataiotaomicron) representatives for their ability to adapt to iron deplete and iron replete conditions. Our transcriptomics and comparative genomics analysis show that many iron-regulated mechanisms are conserved within the phylum. They include genes upregulated in low iron, as follows: (flavodoxin), (hemin uptake operon), and loci encoding ABC transporters. Downregulated genes were (ferredoxin), (rubrerythrin), (succinate dehydrogenase/fumarate reductase), (oxoglutarate oxidoreductase/dehydrogenase), and (pyruvate:ferredoxin/flavodoxin oxidoreductase). Some genus-specific mechanisms, such as the of B. thetaiotaomicron coding for carbohydrate metabolism and the coding for xenosiderophore utilization were also identified. While all bacteria tested in our study had the operon coding for nitrite reduction and were able to reduce nitrite levels present in culture media, the expression of the operon was iron dependent only in B. thetaiotaomicron. It is noteworthy that we identified a significant overlap between regulated genes found in our study and the B. thetaiotaomicron colitis study (W. Zhu, M. G. Winter, L. Spiga, E. R. Hughes et al., Cell Host Microbe 27:376-388, 2020, http://dx.doi.org/10.1016/j.chom.2020.01.010). Many of those commonly regulated genes were also iron regulated in the oral bacterial genera. Overall, this work points to iron being the master regulator enabling bacterial persistence in the host and paves the way for a more generalized investigation of the molecular mechanisms of iron homeostasis in . are an important group of anaerobic bacteria abundant both in the oral and gut microbiomes. Although iron is a required nutrient for most living organisms, the molecular mechanisms of adaptation to the changing levels of iron are not well known in this group of bacteria. We defined the iron stimulon of by examination of the transcriptomic response of Porphyromonas gingivalis and Prevotella intermedia (both belong to the oral microbiome) and Bacteroidetes thetaiotaomicron (belongs to the gut microbiome). Our results indicate that many of the iron-regulated operons are shared among the three genera. Furthermore, using bioinformatics analysis, we identified a significant overlap between our studies and transcriptomic data derived from a colitis study, thus underscoring the biological significance of our work. Defining the iron-dependent stimulon of can help to identify the molecular mechanisms of iron-dependent regulation as well as better understand the persistence of the anaerobes in the human host.
Topics: Humans; Bacteroidetes; Ferredoxins; Flavodoxin; Nitrites; Porphyromonas gingivalis; Iron; Iron Deficiencies; Colitis; Inflammation
PubMed: 37314331
DOI: 10.1128/spectrum.04733-22 -
Journal of International Society of... 2024This narrative review aimed at identifying the existing scientific literature investigating periodontitis and neuropathic diseases. (Review)
Review
AIM
This narrative review aimed at identifying the existing scientific literature investigating periodontitis and neuropathic diseases.
MATERIALS AND METHODS
A search of the literature published between 2000 and 2022 was carried out in the electronic databases of Scopus and PubMed. Studies in which the eligible articles were mainly published in English were included. Descriptive correlational studies, case-control studies, comparative studies, and cohort studies were also included. The following main keywords were used: "Neuropathic diseases," "Periodontitis," "Alzheimer's disease," and "Porphyromonas gingivalis."
RESULTS
This narrative review found that cognitively impaired persons with severe periodontitis had a higher prevalence and incidence of periodontal diseases than the rest of the population. A significant positive correlation of salivary interleukin (IL)-1beta and immediate recall scores involved in cognition was also evident. It indicates that the most investigated parameter was whether there is any common link between periodontal disease and neurodegeneration. No randomized controlled clinical studies were found in the current literature review.
CONCLUSIONS
Based on the literature reviewed, there is currently no strong scientific evidence to support or discourage the cause-effect relationship of periodontal diseases and neurodegenerative diseases.
PubMed: 38559636
DOI: 10.4103/jispcd.jispcd_68_22