Role of sulfide in oral microbiota-host interactions that promote periodontitis

硫化物在促进牙周炎的口腔微生物群与宿主相互作用中的作用

• 批准号: 10828614
• 负责人: Apollo Stacy
• 金额: $ 16.1万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-27 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10828614
• 关键词: Abscess; Actinobacillus actinomycetemcomitans; Administrative Supplement; Adult; Aerobic; Aerobic Bacteria; Affect; Alveolar Bone Loss; Amino Acids; Anaerobic Bacteria; Antibodies; Award; Bilophila wadsworthia; Biological Assay; Bismuth; Cell Respiration; Communicable Diseases; Communities; Consumption; Cysteine; Data; Detection; Diabetes Mellitus; Disease; Excretory function; Flow Cytometry; Formulation; Funding; Fusobacterium nucleatum; Genetic; Goals; Growth; Health; Health Benefit; Heart Diseases; Human; Hydrogen Sulfide; Immune response; Immunity; Immunology; In Vitro; Individual; Inflammation; Inflammatory; Interleukin-6; Interleukins; Invaded; Knowledge; Ligature; Literature; Malignant Neoplasms; Mediating; Mentors; Metabolic; Methionine; Modeling; Mus; National Institute of Dental and Craniofacial Research; Oral; Oral Microbiology; Oral cavity; Oral health; Oxidants; Parents; Pathogenicity; Pathology; Periodontal Diseases; Periodontitis; Pharmaceutical Preparations; Production; Reporting; Research; Resistance; Respiration; Risk; Role; Scholars Program; Sulfides; Sulfur; Supervision; T-Lymphocyte; Taurine; Testing; Therapeutic; Thigh structure; Tissues; Tooth Loss; Tooth structure; alveolar bone; antimicrobial; bacterial genetics; bone loss; co-infection; comorbidity; cytokine; dietary; dietary supplements; dysbiosis; falls; fitness; global health; host microbiota; human disease; immunopathology; in vivo; member; microbial; microbiota; mouse model; mutant; neutrophil; oral immunology; oral microbial community; pathogen; periodontopathogen; prophylactic; response; skills; translational therapeutics

PROJECT SUMMARY/ABSTRACT (for administrative supplement to parent R00 award from NIDCR) Periodontal (gum) disease is one of the most prevalent inflammatory diseases worldwide, affecting nearly 50% of adults in the US alone. Untreated, periodontitis can erode the tissues that support the teeth, ultimately resulting in tooth loss, as well as increased risk for several co-morbidities (e.g., diabetes, heart disease, and cancer). In contrast to classic infectious diseases, periodontitis is triggered by the outgrowth of multiple (rather than individual) “pathogens” - pro-inflammatory, normally low-level constituents of the oral-cavity microbiota. These pathogens expand by metabolically exploiting local tissue damage, while also excreting metabolites that sustain further inflammation. A key example is hydrogen sulfide. This pro-inflammatory metabolite is produced in prolific amounts by periodontal pathogens, due to their increased access to tissue damage-derived, sulfur-containing amino acids - cysteine, methionine, and taurine. In our funded parent award (R00 through NIDCR), we focus on cysteine/methionine and a particular mechanism by which their degradation to sulfide, specifically by the pathogen Fusobacterium nucleatum, can potentially exacerbate periodontitis: inflammation triggered by F. nucleatum-derived sulfide constructs a metabolic niche that enables expansion of a prominent co-pathogen (Aggregatibacter actinomycetemcomitans). Unlike F. nucleatum, other pathogens within the oral microbiota can degrade taurine. Yet, whether sulfide from taurine-degrading pathogens can also contribute to periodontitis has not been explored. This is particularly concerning since taurine is widely consumed as a dietary supplement due to its many purported health benefits. Indeed, in a project supported by the Office of Dietary Supplements (ODS) Research Scholars Program, we recently reported that when provided prophylactically, dietary taurine-derived sulfide can enhance the microbiota’s resistance to invading pathogens. However, in the context of pre-existing inflammation, such as periodontitis, taurine-derived sulfide may instead exacerbate disease. In this ODS administrative supplement, we propose testing this exact possibility. Falling within the scope of our original award, we propose testing whether by a similar mechanism as the cysteine/methionine-degrading pathogen F. nucleatum, the taurine-degrading pathogen Bilophila wadsworthia can enhance periodontal disease. This new information will enhance our original award because it will demonstrate that sulfide’s negative impact on oral health is not restricted to a specific periodontal pathogen (not only F. nucleatum but also B. wadsworthia) nor a specific sulfide precursor (not only cysteine/methionine but also taurine). Most importantly, the new information that will be generated by this administrative supplement will shed light on the potential health risks of a widely consumed dietary supplement (the amino acid taurine) and a context (the prevalent disease periodontitis) in which consumption of this supplement should be avoided.

项目摘要/摘要(用于NIDCR颁发的母公司R00奖励的行政补充) 牙周(牙周)疾病是世界范围内最流行的炎症性疾病之一，影响近50% 仅在美国就有成年人的比例。如果不治疗，牙周炎会侵蚀支持牙齿的组织，最终导致 这会增加牙齿脱落的风险，增加患多种疾病(如糖尿病、心脏病和癌症)的风险。在……里面 与经典的传染病不同，牙周炎是由多发性(而不是 个人)“病原体”--口腔微生物区系中致炎的、通常水平较低的成分。这些 病原体通过新陈代谢利用局部组织损伤进行扩张，同时也排泄出维持 进一步发炎。一个关键的例子是硫化氢。这种促炎代谢物在多产的 牙周病原体的数量，因为它们更多地接触到组织损伤衍生的含硫 氨基酸--半胱氨酸、蛋氨酸和牛磺酸。在我们的资助家长奖(R00至NIDCR)中，我们专注于 半胱氨酸/蛋氨酸及其降解为硫化物的特殊机制，特别是通过 致病菌核梭杆菌可能会加重牙周炎：由F. 核仁衍生的硫化物构建了一个代谢生态位，使突出的共病原得以扩展 (Aggregatibacter放线菌伴生菌)。与核杆菌不同，口腔微生物区系中的其他病原体可以 降解牛磺酸。然而，牛磺酸降解病原体中的硫化物是否也会导致牙周炎 没有被探索过。这一点尤其令人担忧，因为牛磺酸被广泛用作膳食补充剂。 它的许多所谓的健康益处。事实上，在膳食补充剂办公室支持的一个项目中 研究学者计划，我们最近报道，当预防性提供时，饮食中的牛磺酸衍生 硫化物可以增强微生物群对入侵病原体的抵抗力。然而，在先前存在的背景下 炎症，如牙周炎，牛磺酸衍生的硫化物可能反而会加重疾病。在这份正式文件中 行政副刊，我们建议测试这一确切的可能性。属于我们原创的范围 奖，我们建议测试是否通过类似于半胱氨酸/蛋氨酸降解病原菌F. 核霉，牛磺酸降解病原菌华氏毕氏杆菌，可加强牙周疾病。这是一项新的 信息将加强我们最初的奖项，因为它将表明硫化物对口腔的负面影响 健康并不局限于特定的牙周病原体(不仅是核杆菌，也包括沃兹沃斯杆菌)，也不限于 特定的硫化物前体(不仅是半胱氨酸/蛋氨酸，而且还有牛磺酸)。最重要的是，新的信息 这一行政补充将揭示广泛存在的潜在健康风险 摄入的膳食补充剂(氨基酸牛磺酸)和上下文(牙周炎的流行疾病) 这种补充剂应该避免哪种消费。