Local and systemic specific immunity, microbiome and H. pylori infection in child

儿童局部和全身特异性免疫、微生物组和幽门螺杆菌感染

• 批准号: 7701563
• 负责人: STEVEN J CZINN
• 金额: $ 27.64万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-18 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7701563
• 关键词: Adult; Animals; Antibiotics; Antigens; B-Lymphocytes; Bacteria; Biopsy; Child; Developed Countries; Developing Countries; Development; Diagnostic; Disease; Duodenal Ulcer; Dyspepsia; Esophagogastroduodenoscopy; Flow Cytometry; Gastric Adenocarcinoma; Gastric mucosa; Gastric ulcer; Gastritis; Gastroesophageal reflux disease; Genomics; Health; Helicobacter; Helicobacter Infections; Helicobacter pylori; Histologic; Histology; Human; Imagery; Immune response; Immunity; Immunologics; Incidence; Individual; Infection; Inflammation; Integration Host Factors; Investigation; Life; Malignant Neoplasms; Morbidity - disease rate; Mucosal Immunity; Pain; Pathogenesis; Pathology; Patients; Peptic Ulcer; Population; Predisposing Factor; Prevalence; Process; Production; Proton Pump Inhibitors; Regulation; Relative (related person); Resistance; Reverse Transcriptase Polymerase Chain Reaction; Role; Stomach; Testing; Vaccines; Virulence; Virulence Factors; Work; cofactor; cytokine; infancy; malignant stomach neoplasm; microbiome; mortality; mucosa-associated lymphoid tissue lymphoma

Helicobacter pylori (H. pylori) infection of the stomach is responsible for significant amount of morbidity and mortality. Although H. pylori have multiple virulence factors, the host response also contributes to pathogenesis and these host factors vary between individuals. In addition to H. py/on-associated diseases, significant morbidity is associated with non-H. pylori associated gastric afflictions. Dyspepsia is the most common gastric ailment among adults and children yet there is no clear association with H. pylori. New genomics evidence on bacterial isolates indicates there are other populations of bacteria in the gastric mucosa. These other bacterial genera or species might help explain why gastric maladies vary between populations and between individuals. They might also serve as an important co-factor in H. py/on-associated diseases. We hypothesize that the gastric mucosa harbors resident populations of non-Helicobacter bacteria that vary among individuals and serve as important cofactors in determining the gastric health of the host. These bacteria, together with the host immune response work cumulatively to influence the incidence and character of gastric malignancies. This hypothesis will be tested by accomplishing the following three specific aims. 1) Compare the immune responses to H. pylori in children and adults undergoing diagnostics for presumptive H. pylori infection. These studies will help us assess the relative importance of the key effector immune responses in influencing the development of H. pylori infection in children and adults. 2. Assess the potential importance of the gastric microbiome in influencing the development and the degree of inflammation associated with H. pylori infection in children and adults. The results from these studies will be correlated with the immune responses in subjects in Aim 1 to determine the association of the gastric microbiome with specific immune responses to H. pylori infection in children and adults. 3. Assess the role of specific immunity and gastric microflora either in isolation or in concert with H. pylori infection, in influencing the development of gastroesophageal reflux disease, dyspepsia, gastric ulcers, duodenal ulcers and gastric cancer. These studies will generate new information about immunologic function and regulation in the stomach which would subsequently allow for comparison to gut immunity. Additionally, new information on the presence and possible contribution of other bacteria on gastric health and disease will provide significant advances for treatment of patients presenting with gastric pathology

胃幽门螺杆菌（H. Pylori）的胃感染负责大量发病率和 死亡。尽管幽门螺杆菌具有多种毒力因子，但宿主反应也有助于 发病机理和这些宿主因素在个体之间有所不同。除了H. py/与亲自相关的疾病外， 明显的发病率与非H有关。幽门螺杆菌相关的胃痛。消化不良是最大的 成人和儿童中常见的胃病，但与幽门螺杆菌没有明显的关联。新的 基因组学关于细菌分离株的证据表明胃中还有其他细菌种群 粘膜。这些其他细菌属或物种可能有助于解释为什么胃病之间有所不同 种群和个人之间。它们也可能是H. py/on-On-onseped的重要共同因素 疾病。我们假设胃粘膜藏有非螺旋细菌的居民种群 在个体之间有所不同，并作为确定宿主胃健康的重要辅助因子。 这些细菌，以及宿主免疫反应累积起作用，以影响发生率和 胃恶性肿瘤的特征。该假设将通过完成以下三个来检验 具体目标。 1）比较接受诊断的儿童和成人对幽门螺杆菌的免疫反应 用于推定幽门螺杆菌感染。这些研究将有助于我们评估关键的相对重要性 效应子免疫反应在影响儿童和成人幽门螺杆菌感染的发展时。 2。 评估胃微生物组在影响发展和程度的潜在重要性 儿童和成人中与幽门螺杆菌感染有关的炎症。这些研究的结果将是 与AIM 1中受试者中的免疫反应相关，以确定胃的关联 微生物组对儿童和成人的幽门螺杆菌感染具有特异性免疫反应。 3。评估角色 特异性免疫和胃微生物群体分离或与幽门螺杆菌感染一致 影响胃食管反流疾病，消化不良，胃溃疡，十二指肠溃疡的发展 和胃癌。这些研究将产生有关免疫功能和调节的新信息 在胃中，随后可以与肠道免疫进行比较。另外，新的 有关其他细菌对胃健康和疾病的存在和可能贡献的信息 为患有胃病理学的患者提供了重大进展