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父母R00奖的行政补充） 牙周（口香糖）疾病是全球最普遍的炎症性疾病之一，影响了近50％ 仅在美国的成年人。未经处理的牙周炎会侵蚀支撑牙齿的组织，最终导致 在牙齿丧失方面，以及多种合并症（例如糖尿病，心脏病和癌症）的风险增加。 与经典的传染病形成鲜明对比，牙周炎是由多重生长引起的（而不是 个体）“病原体” - 促炎性，通常低级构成口腔腔微生物群。这些 病原体通过代谢利用局部组织损害扩展 进一步的炎症。一个关键的例子是硫化氢。这种促炎性代谢产物是多产的 由于牙周病原体的量增加，由于它们增加了组织损伤的含硫 氨基酸 - 半胱氨酸，蛋氨酸和牛磺酸。在我们资助的父母奖（r00到nidcr）中，我们专注于 半胱氨酸/蛋氨酸和一种特定的机制，其降解为硫化物，特别是由 病原体核细菌核毒菌可能会加剧牙周炎：F。 核衍生的硫化物构建了一种代谢细分市场，可以扩展突出的副病原 （聚集的放线菌ceTemComitans）。与F. nutleatum不同，口服微生物群中的其他病原体可以 退化牛磺酸。然而，来自牛磺酸降解病原体的硫化物是否也会导致牙周炎 没有探索。这尤其关注，因为牛磺酸被广泛用作饮食补充剂。 具有许多声称的健康益处。确实，在饮食补充剂办公室（ODS）支持的项目中 研究学者计划，我们最近报道说，饮食牛磺酸的预防性提供 硫化物可以增强微生物群对入侵病原体的抗性。但是，在预先存在的背景下 炎症，例如牙周炎，牛磺酸衍生的硫化物可能加剧疾病。在这个ODS中 行政补充，我们建议测试这种确切的可能性。属于我们原始的范围 奖项，我们建议通过类似的机制与半胱氨酸/蛋氨酸降解病原体F进行测试。 NucleAtum，牛磺酸病原体双毛虫Wadsworthia可以增强牙周疾病。这个新 信息将增强我们的原始奖项，因为它将证明硫化物对口腔的负面影响 健康不仅限于特定的牙周病原体（不仅是F. nucleatum，而且还限于Wadsworthia的B. wadsworthia）或 特异性硫化物前体（不仅是半胱氨酸/蛋氨酸，而且也是牛磺酸）。最重要的是，新信息 这种行政补充剂将产生，这将阐明广泛的健康风险 食用饮食补充剂（氨基酸牛磺酸）和环境（普遍的疾病牙周炎） 应避免使用该补充的哪种消费。