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

基本信息

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
项目类别：
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

项目摘要

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（NIDCR 家长 R00 奖励的行政补充）牙周（牙龈）疾病是全球最常见的炎症性疾病之一，影响近 50% 仅在美国，未经治疗的成年人就有牙周炎会侵蚀支撑牙齿的组织，最终导致牙周炎。牙齿脱落，以及多种并发症（例如糖尿病、心脏病和癌症）的风险增加。与典型的传染病相比，牙周炎是由多种牙周炎（而不是牙周炎）的生长引发的。个体）“病原体” - 口腔微生物群的促炎成分，通常含量较低。病原体通过代谢利用局部组织损伤来扩张，同时还分泌维持生命的代谢物一个重要的例子是硫化氢，这种促炎代谢物是大量产生的。牙周病原体的数量，因为它们更多地接触组织损伤衍生的含硫物质氨基酸 - 半胱氨酸、蛋氨酸和牛磺酸在我们资助的家长奖（R00 至 NIDCR）中，我们重点关注氨基酸。半胱氨酸/蛋氨酸以及它们降解为硫化物的特定机制，特别是通过病原体具核梭杆菌，可能会加剧牙周炎：由具核梭杆菌引发的炎症。核杆菌衍生的硫化物构建了一个代谢生态位，使一种重要的共同病原体得以扩展（Aggregatibacter actinomycetemcomitans）与具核梭菌不同，口腔微生物群中的其他病原体可以。然而，牛磺酸降解病原体中的硫化物是否也会导致牙周炎？这一点尤其令人担忧，因为牛磺酸作为膳食补充剂被广泛食用。事实上，在膳食补充剂办公室 (ODS) 支持的一个项目中，它具有许多声称的健康益处。研究学者计划，我们最近报告说，当预防性地提供时，膳食牛磺酸衍生的硫化物可以增强微生物群对入侵病原体的抵抗力。在这种消耗臭氧层物质中，牛磺酸衍生的硫化物可能会加重炎症，例如牙周炎。行政补充，我们建议在我们原来的范围内测试这种确切的可能性。奖项中，我们建议测试是否通过与半胱氨酸/蛋氨酸降解病原体 F 类似的机制。 nucleatum，牛磺酸降解病原体 Bilophila wadsworthia 可以加剧牙周病。这些信息将增强我们最初的奖项，因为它将证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（不仅包括具核梭菌，还包括沃兹沃斯芽孢杆菌），也不局限于特定的牙周病原体。特定的硫化物前体（不仅是半胱氨酸/蛋氨酸，还有牛磺酸）。最重要的是，新信息。该行政补充文件将产生的结果将揭示广泛的潜在健康风险消耗的膳食补充剂（氨基酸牛磺酸）和背景（流行病牙周炎）应避免食用这种补充剂。