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.

项目概要/摘要（NIDCR对母公司R 00奖的行政补充） 牙周病是世界范围内最常见的炎症性疾病之一， 仅在美国的成年人中。未经治疗，牙周炎会侵蚀支持牙齿的组织，最终导致 牙齿脱落，以及几种合并症的风险增加（例如，糖尿病、心脏病和癌症）。在 与典型的传染病相反，牙周炎是由多种（而不是由牙周炎引起的）细菌的生长引起的。 个体）“病原体”-促炎性的，通常是口腔微生物群的低水平成分。这些 病原体通过代谢利用局部组织损伤而扩张，同时也分泌维持 进一步的炎症。一个重要的例子是硫化氢。这种促炎代谢物是在多产的 量的牙周病原体，由于他们增加了获得组织损伤衍生的，含硫 氨基酸-半胱氨酸、蛋氨酸和牛磺酸。在我们的资助父母奖（R 00通过NIDCR），我们专注于 半胱氨酸/甲硫氨酸以及它们降解为硫化物的特定机制，特别是通过半胱氨酸/甲硫氨酸的降解， 病原体具核梭杆菌可能会加重牙周炎：由F. 核衍生硫化物构建了一个代谢生态位，使一个突出的共同病原体能够扩张 （伴放线聚集杆菌）。与F.口腔微生物群中的其他病原体可 降解牛磺酸。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， 没有被探索过。这是特别令人关注的，因为牛磺酸被广泛用作膳食补充剂， 它的许多声称的健康益处。事实上，在膳食补充剂办公室（ODS）支持的一个项目中， 研究学者计划，我们最近报告说，当提供膳食牛磺酸衍生 硫化物可以增强微生物群对入侵病原体的抵抗力。然而，在预先存在的背景下 炎症，如牙周炎，牛磺酸衍生的硫化物反而可能加剧疾病。在混乱办 行政补充，我们建议测试这种确切的可能性。属于我们最初的 奖，我们建议测试是否通过半胱氨酸/甲硫氨酸降解病原体F。 牛磺酸降解病原体Bilophila wadsaccharia可以增强牙周病。这个新 信息将增强我们最初奖项，因为它将证明硫化物对口腔的负面影响， 健康不限于特定的牙周病原体（不仅是F.有核质，但也有B。wadsouchia）nor a 特定硫化物前体（不仅是半胱氨酸/甲硫氨酸，还有牛磺酸）。最重要的是，新的信息 这将产生的行政补充将揭示潜在的健康风险， 消耗的膳食补充剂（氨基酸牛磺酸）和背景（流行疾病牙周炎）， 应该避免这种补充剂的消耗。