Periodontitis and Alzheimer’s disease: oral systemic link still on the rise?

doi: 10.1111/j.1741‐2358.2012.00660.x Periodontitis and Alzheimer’s disease: Oral systemic link still on the rise? Over the past few years, there has been a rapid rise in the older segments of the world population, which has brought along with it a major health concern: dementia. Alzheimer’s disease, considered to be the most common cause of dementia, has become a prospect feared by the elderly. Inflammation of the brain is strongly implicated in Alzheimer’s disease which could be enhanced by systemic inflammation. Periodontitis being a chronic inflammatory condition, which can cause systemic inflammation, the question is whether chronic periodontitis can initiate or hasten the rate of progression of Alzheimer’s disease in susceptible individuals. In this article, the authors outline the proposed oral systemic link between periodontitis and Alzheimer’s disease.     

链球菌-韦荣菌共生对系统性疾病的诊断价值研究

口腔是人体生理功能的窗口,也是种类和数量繁多的微生物库.口腔微生态变化能够反映宿主与环境因素的相互作用,进而影响机体健康和疾病的进展.其中,链球菌属(Streptococcus)和韦荣菌属(Veillonella)是口腔最早的定殖菌和典型共生菌,共同参与口腔早期生物膜形成.大量研究显示,链球菌和韦荣菌共生失调不仅与龋病...     

口腔微生物与阿尔茨海默病相关性的研究进展

口腔微生物组是人体五大菌库之一,其微生态失衡不仅在牙周炎和龋齿等口腔疾病中发挥主要作用,还与全身诸多疾病紧密相关。阿尔茨海默病（Alzheimer′s disease,AD）是一种神经系统退行性疾病,随着社会人口老龄化的加剧,其防治已成为严重的公共卫生问题。大量研究表明,AD与某些口腔致病菌及其微生态失衡显著相关。本文就口腔微生物与AD的关系作一综述,总结了口腔微生物影响AD的可能机制,并在此基础上初步推测不同的微生物与AD间的潜在关系。为进一步治疗和预防AD,人们除了关注AD患者大脑的病理改变外,还应关注患者的口腔微生态平衡。

     

Ocular disease in patients with ANCA-positive vasculitis

Anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis—the term recently applied to Wegener's granulomatosis—is a rare multi-system inflammation characterized by necrotizing granulomas and vasculitis. We investigated the ocular manifestations of this disease in a group of patients drawn from five inflammatory eye disease clinics across the United States. Of 8,562 persons with ocular inflammation, 59 individuals were diagnosed with ANCA-positive vasculitis; 35 males and 21 females, aged 16 to 96 years, were included in this study. Ocular diagnoses were scleritis (75.0%), uveitis (17.9%), and other ocular inflammatory conditions (33.9%) including peripheral ulcerative keratitis and orbital pseudotumor. Mean duration of ocular disease was 4.6 years. Oral corticosteroids and other systemic immunosuppressive agents were used by 85.7% and 78.5% of patients, respectively. Over time, patients with ANCA-positive vasculitis experienced 2.75-fold higher mortality than other patients with inflammatory eye disease.     

Pyostomatitis vegetans associated with inflammatory bowel disease--report of two cases

Pyostomatitis vegetans (PV) is a rare, chronic mucocutaneous disorder associated with inflammatory bowel disease (IBD). Oral lesions of PV are distinct and present as multiple white or yellow pustules with an erythematous base that coalesce and undergo necrosis to form a typical "snail tracks" appearance. Two cases of PV associated with IBD--one with Crohn's disease (CD) and the other with ulcerative colitis (UC) are reported. In the first case, adalimumab therapy brought the oral and gastrointestinal manifestations to complete remission. In the second case, the remission was achieved with systemic steroid therapy, but the disease relapsed after therapy discontinuation. Azathioprine was added leading to sustained remission of PV. Because of persistent active intestinal manifestation of UC, in spite of immunosuppressive therapy, infliximab was introduced. With the therapy remission of intestinal manifestation of UC was achieved as well. Our cases confirm previously reported good experience with immunomodulators and biologics in the treatment of PV. But, before using them we have to exclude an infectious etiology of oral lesions.     

Prelude to oral microbes and chronic diseases: past,present and future

Associations between oral and systemic health are ancient. Oral opportunistic bacteria, particularly, Porphyromonas gingivalis and Fusobacterium nucleatum, have recently been deviated from their traditional roles as periodontal pathogens and arguably ascended to central players based on their participations in complex co-dependent mechanisms of diverse systemic chronic diseases risk and pathogenesis, including cancers, rheumatoid-arthritis, and diabetes.     

A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including neoplastic, autoimmune, and chronic inflammatory diseases. Emerging evidence implicates pathogen-induced chronic inflammation in the development and progression of chronic diseases with a wide variety of clinical manifestations. Due to the complex and multifactorial etiology of chronic disease, designing experiments for proof of causality and the establishment of mechanistic links is nearly impossible in humans. An advantage of using animal models is that both genetic and environmental factors that may influence the course of a particular disease can be controlled. Thus, designing relevant animal models of infection represents a key step in identifying host and pathogen specific mechanisms that contribute to chronic inflammation.Here we describe a mouse model of pathogen-induced chronic inflammation at local and systemic sites following infection with the oral pathogen Porphyromonas gingivalis, a bacterium closely associated with human periodontal disease. Oral infection of specific-pathogen free mice induces a local inflammatory response resulting in destruction of tooth supporting alveolar bone, a hallmark of periodontal disease. In an established mouse model of atherosclerosis, infection with P. gingivalis accelerates inflammatory plaque deposition within the aortic sinus and innominate artery, accompanied by activation of the vascular endothelium, an increased immune cell infiltrate, and elevated expression of inflammatory mediators within lesions. We detail methodologies for the assessment of inflammation at local and systemic sites. The use of transgenic mice and defined bacterial mutants makes this model particularly suitable for identifying both host and microbial factors involved in the initiation, progression, and outcome of disease. Additionally, the model can be used to screen for novel therapeutic strategies, including vaccination and pharmacological intervention.     

B7.2 (CD86) but not B7.1 (CD80) costimulation is required for the induction of low dose oral tolerance.

Oral administration of Ag leads to systemic unresponsiveness (oral tolerance) to the fed Ag. Oral tolerance is mediated through active suppression by Th2 or TGF-beta-secreting cells or clonal anergy/deletion, depending on the Ag dose used, with low dose favoring active suppression and high dose favoring anergy/deletion. The nature of APC and inductive events leading to the generation of oral tolerance have not been well defined. To determine the role of costimulatory molecules in the induction of oral tolerance, we have tested the effect of anti-B7.1 or anti-B7.2 mAb on the induction of tolerance by both high and low dose Ag feeding regimens. Our results show that the B7.2 molecule is critical for the induction of low-dose oral tolerance. Injection of anti-B7.2 but not anti-B7.1 intact Ab or Fab fragments inhibited the oral tolerance induced by low-dose (0.5 mg) but not high-dose OVA (25 mg) feeding. In addition, anti-B7.2, but not anti-B7.1, inhibited secretion of TGF-beta, one of the primary cytokines that mediates low-dose oral tolerance. Finally, in the in vivo model of experimental allergic encephalomyelitis, anti-B7.2 mAb treatment abrogated protection offered against disease by low-dose myelin basic protein feeding, while anti-B7.1 had no effect. Anti B7.2 had no effect on disease suppression by high-dose oral Ag. These data demonstrate that B7.2 costimulatory molecules play an essential role in the induction of low-dose oral tolerance.     

Daily variation of oral malodour and related factors in community-dwelling elderly Thai

doi: 10.1111/j.1741‐2358.2011.00593.x Daily variation of oral malodour and related factors in community‐dwelling elderly Thai Objectives: The purposes of this study were (i) to estimate the prevalence of oral malodour, (ii) to evaluate the daily variation of oral malodour and (iii) to assess associations of volatile sulphur compound (VSC) concentrations with socio‐demographics, health behaviours and oral health status in community‐dwelling elderly Thai. Methods: The subjects were 428 dentate elderly people (67.6 ± 5.6 years) living in Phitsaulok, Thailand. Information on their socio‐demographics, general health and health behaviours was obtained by a questionnaire. Their dental condition, periodontal status and tongue coating were clinically examined. Their flow rates and the pH of unstimulated saliva were also assessed. Oral malodour was measured at four different times of day using an Oral Chroma?. Results: The proportions of subjects diagnosed with oral malodour using the thresholds of H₂S, CH₃SH and (CH₃)₂S were 60.5%, 62.9% and 80.7%, respectively. Concentrations of H₂S showed significant daily variation. Linear regression analysis demonstrated the following significant associations: (i) oral malodour from H₂S and thickness of the tongue coating, (ii) oral malodour from CH₃SH and periodontal pocket depth of 5 mm or more and the presence of gingival bleeding and (iii) oral malodour from (CH₃)₂S and systemic disease, medications and thickness of the tongue coating. Discussion: Oral malodour was shown to be prevalent among the elderly. Daily variation was observed in the concentration of H₂S. Tongue coating, periodontal disease, systemic diseases and medications were related to oral malodour. Therefore, these factors should be taken into consideration in oral malodour treatment and prevention programmes for the elderly.     

Oral microbiomes: more and more importance in oral cavity and whole body

Microbes appear in every corner of human life, and microbes affect every aspect of human life. The human oral cavity contains a number of different habitats. Synergy and interaction of variable oral microorganisms help human body against invasion of undesirable stimulation outside. However, imbalance of microbial flora contributes to oral diseases and systemic diseases. Oral microbiomes play an important role in the human microbial community and human health. The use of recently developed molecular methods has greatly expanded our knowledge of the composition and function of the oral microbiome in health and disease. Studies in oral microbiomes and their interactions with microbiomes in variable body sites and variable health condition are critical in our cognition of our body and how to make effect on human health improvement.     

Gingival and Periodontal Parameters in a Population of Healthy Adults, 22–90 Years of Age1

There are little data concerning the periodontal status of aging individuals free of systemic disease and medication utilization. In the present study 55 healthy male and female, non-medicated adults between the ages of 22 and 90 were evaluated by comparing gingival and periodontal parameters. The results indicate greater proportions of sites with dental plaque, calculus, gingival bleeding and recession, and attachment loss in the oldest age group. The progression of these changes from young to middle to old age was not uniform. Attachment loss showed the most significant age-related changes. Results from this small, cross-sectional study of healthy individuals are generally comparable to findings reported from the NIDR 1985 National Survey of Oral Health in U.S. Adults.     

Exogenous ketone ester administration attenuates systemic inflammation and reduces organ damage in a lipopolysaccharide model of sepsis

AimsSepsis is a life-threatening condition of organ dysfunction caused by dysregulated inflammation which predisposes patients to developing cardiovascular disease. The ketone β-hydroxybutyrate is reported to be cardioprotective in cardiovascular disease and this may be due to their signaling properties that contribute to reducing inflammation. While exogenous ketone esters (KE) increase blood ketone levels, it remains unknown whether KEs can reduce the enhanced inflammatory response and multi-organ dysfunction that is observed in sepsis. Thus, this study assesses whether a recently developed and clinically safe KE can effectively improve the inflammatory response and organ dysfunction in sepsis.Methods and resultsTo assess the anti-inflammatory effects of a KE, we utilized a model of lipopolysaccharide (LPS)-induced sepsis in which an enhanced inflammatory response results in multi-organ dysfunction. Oral administration of KE for three days prior to LPS-injection significantly protected mice against the profound systemic inflammation compared to their vehicle-treated counterparts. In assessing organ dysfunction, KE protected mice from sepsis-induced cardiac dysfunction as well as renal dysfunction and fibrosis. Furthermore, KE administration attenuated the sepsis-induced inflammation in the heart, kidney, and liver. Moreover, these protective effects occurred independent of changes to enzymes involved in ketone metabolism.ConclusionThese data show that the use of an exogenous KE attenuates the dysregulated systemic and organ inflammation as well as organ dysfunction in a model of severe inflammation. We postulate that this exogenous KE is an appealing and promising approach to capitalize on the protective anti-inflammatory effects of ketones in sepsis and/or other inflammatory responses.     

The role of oral acyclovir in the management of genital herpes simplex.

Oral acyclovir is an antiviral nucleoside analogue that has recently been released in Canada for use in selected patients with genital infections by the herpes simplex virus. First episodes of genital herpes should be treated with oral acyclovir as soon as the diagnosis is considered. Most people with recurrent genital herpes do not require systemic drug therapy. Selected patients with severe or long-lasting recurrences, recurrences associated with long prodromal periods (greater than 12 to 24 hours) or systemic complications such as erythema multiforme and eczema herpeticum may receive measurable benefit from treatment at the onset of symptoms. In most patients frequently recurrent disease can be suppressed with long-term therapy. Since long-term safety beyond 1 year has not been established, suppressive therapy should be stopped at least once per year to reassess the recurrence pattern. Acyclovir has not been adequately tested for safety in pregnancy and should not be prescribed for pregnant women unless the potential benefits outweigh the risks. Careful attention to disease severity, accurate diagnosis and exclusion of other causes of genital lesions will ensure that the drug is used only when beneficial.     

Effect of oral immunization with Aeromonas hydrophila ghosts on protection against experimental fish infection

Aims:  To investigate whether oral immunization with Aeromonas hydrophila ghosts (AHG) vaccine can elicit mucosal and systemic immune responses of Carp ( Carassius auratus gibelio ) compared to conventional formalin-killed bacteria (FKC).
Methods and Results:  Fish were fed diets coated with AHG, FKC or phosphate buffered saline (PBS) alone, after immunization, more antigen-specific antibody was significantly detected in serum and intestinal mucus in AHG group than FKC group and PBS group. In addition, after challenged with the parent strain J-1, the survival of bacterial ghost-vaccinated fish was higher than PBS group and FKC group, the relative per cent survival (RPS) being 76·8%, 58·9%, respectively.
Conclusions:  Oral immunization with A. hydrophila ghosts can elicit systemic and mucosal adaptive immune responses and has higher potential to induce protective adaptive immunity than normal vaccine.
Significance and Impact of the Study:  Oral immunization with bacterial ghosts is a promising new solution with potential application to prevent diseases in fish.     

A review of oral vaccination with transgenic vegetables

Mucosal immunization of the gastrointestinal tract is an effective way to stimulate local and systemic immune responses. Oral vaccines must be formulated in such a way that antigens are protected as they pass through the adverse environment of the stomach and are delivered to the mucosal inductive sites. Vaccine antigens cloned into edible transgenic plants are a promising new delivery system for oral vaccines. Such vaccines could be safe, inexpensive, and multicomponent.     

Commensal Streptococcus mitis is a unique vector for oral mucosal vaccination

The development of vaccine approaches that induce mucosal and systemic immune responses is critical for the effective prevention of several infections. Here, we report on the use of the abundant human oral commensal bacterium Streptococcus mitis as a delivery vehicle for mucosal immunization. Using homologous recombination we generated a stable rS. mitis expressing a Mycobacterium tuberculosis protein (Ag85b). Oral administration of rS. mitis in gnotobiotic piglets resulted in efficient oral colonization and production of oral and systemic anti-Ag85b specific IgA and IgG antibodies. These results support that the commensal S. mitis is potentially a useful vector for mucosal vaccination.     

C5a receptor-targeting ligand-mediated delivery of dengue virus antigen to M cells evokes antigen-specific systemic and mucosal immune responses in oral immunization

Oral mucosal immunization is a feasible and economic vaccination strategy. In order to achieve a successful oral mucosal vaccination, antigen delivery to gut immune inductive site and avoidance of oral tolerance induction should be secured. One promising approach is exploring the specific molecules expressed on the apical surfaces of M cells that have potential for antigen uptake and immune stimulation. We previously identified complement 5a receptor (C5aR) expression on human M-like cells and mouse M cells and confirmed its non-redundant role as a target receptor for antigen delivery to M cells using a model antigen. Here, we applied the OmpH ligand, which is capable of targeting the ligand-conjugated antigen to M cells to induce specific mucosal and systemic immunities against the EDIII of dengue virus (DENV). Oral immunization with the EDIII–OmpH efficiently targeted the EDIII to M cells and induced EDIII-specific immune responses comparable to those induced by co-administration of EDIII with cholera toxin (CT). Also, the enhanced responses by OmpH were characterized as Th2-skewed responses. Moreover, oral immunization using EDIII–OmpH did not induce systemic tolerance against EDIII. Collectively, we suggest that OmpH-mediated targeting of antigens to M cells could be used for an efficient oral vaccination against DENV infection.     

Clinical applications of breast cancer metabolomics using high-resolution magic angle spinning proton magnetic resonance spectroscopy (HRMAS 1H MRS): systematic scoping review

Metabolomics - Oral microflora is a well-orchestrated and acts as a sequential defense mechanism for any infection related to oral disease. Chronic periodontitis is a disease of a microbial...     

Oral lichen planus: a microbiologist point of view

International Microbiology - Oral lichen planus (OLP) is a chronic disease of uncertain etiology, although it is generally considered as an immune-mediated disease that affects the mucous membranes...     

Oral health and frailty in the medieval English cemetery of St Mary Graces

The analysis of oral pathologies is routinely a part of bioarcheological and paleopathological investigations. Oral health, while certainly interesting by itself, is also potentially informative about general or systemic health. Numerous studies within modern populations have shown associations between oral pathologies and other diseases, such as cardiovascular disease, certain types of cancer, and pulmonary infections. This article addresses the question of how oral health was associated with general health in past populations by examining the relationship between two oral pathologies (periodontal disease and dental caries) and the risk of mortality in a cemetery sample from medieval England. The effects of periodontitis and dental caries on risk of death were assessed using a sample of 190 individuals from the St Mary Graces cemetery, London, dating to ～AD 1350–1538. The results suggest that the oral pathologies are associated with elevated risks of mortality in the St Mary Graces cemetery such that individuals with periodontitis and dental caries were more likely to die than their peers without such pathologies. The results shown here suggest that these oral pathologies can be used as informative indicators of general health in past populations. Am J Phys Anthropol, 2010. © 2009 Wiley‐Liss, Inc.