Disappearing gastrointestinal microbiota in epidemic obesity.

流行性肥胖症中胃肠道微生物群的消失。

• 批准号: 8780962
• 负责人: MARTIN J BLASER
• 金额: $ 121.64万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8780962
• 关键词: Age; Antibiotic Therapy; Antibiotics; Bacteria; Birth; Child; Communities; Developed Countries; Development; Developmental Process; Dose; Endoscopy; Enrollment; Ensure; Epidemic; Epithelium; Feces; Gastrointestinal tract structure; Gender; Goals; Health; Helicobacter pylori; Homeostasis; Hormonal; Hormones; Human; Human Microbiome; Immunity; Incidence; Indigenous; Inflammation; Inherited; Insulin; Insulin-Like Growth Factor I; Intestines; Leptin; Life; Metabolic; Modernization; Monozygotic Twinning; Monozygotic twins; Mothers; Mus; Netherlands; New York City; Obesity; Phenotype; Physiology; Play; Population; Risk Factors; Role; Sampling; School-Age Population; Specimen; Stomach; Study Subject; Testing; Twin Multiple Birth; United States; base; cohort; cytokine; fasting plasma glucose; gastrointestinal; ghrelin; microbial; microbiome; next generation; obesity in children; upper GI series; young adult; Age; Antibiotic Therapy; Antibiotics; Bacteria; Birth; Child; Communities; Developed Countries; Development; Developmental Process; Dose; Endoscopy; Enrollment; Ensure; Epidemic; Epithelium; Feces; Gastrointestinal tract structure; Gender; Goals; Health; Helicobacter pylori; Homeostasis; Hormonal; Hormones; Human; Human Microbiome; Immunity; Incidence; Indigenous; Inflammation; Inherited; Insulin; Insulin-Like Growth Factor I; Intestines; Leptin; Life; Metabolic; Modernization; Monozygotic Twinning; Monozygotic twins; Mothers; Mus; Netherlands; New York City; Obesity; Phenotype; Physiology; Play; Population; Risk Factors; Role; Sampling; School-Age Population; Specimen; Stomach; Study Subject; Testing; Twin Multiple Birth; United States; base; cohort; cytokine; fasting plasma glucose; gastrointestinal; ghrelin; microbial; microbiome; next generation; obesity in children; upper GI series; young adult

DESCRIPTION (provided by applicant): The incidence of obesity has been rapidly increasing in the United States and other developed countries. Our hypothesis is that changes are occurring in the indigenous microbial populations that are of ancient origin, due to modernization including antibiotic exposure. Our hypothesis is that these changes in the composition of the microbiome are at least in part playing a role in the increasing incidence of obesity. More specifically, we also hypothesize that common antibiotic treatments are incidentally causing changes in the composition of metabolically active gastrointestinal bacterial populations, and that the effects may be sequential in which maternal changes are then inherited by the next generation. We will test this hypothesis by studying both the colonic microbiota, and Helicobacter pylori, the dominant gastric bacteria that interact with gastric epithelium, which produces hormones (leptin and ghrelin) that are involved in energy homeostasis. We propose 5 studies. Study A1 will be to assess the association of maternal H. pylori status on the development of childhood obesity in a presently enrolled cohort in The Netherlands. Study A2 will examine the relationship in children of H. pylori status and the physiology of gastric hormones, inflammation, and immunity. Study A3 will assess the changes in hormonal and metabolic phenotypes in young adults due to clinically indicated eradication of H. pylori. Study B1 will assess the effects on young mice of the continuous administration of low antibiotic doses in terms of metabolic and hormonal phenotypes. Study B2 will examine the development of the intestinal microbiota over the first year of life in singletons and twins, and will assess the effects of antibiotic perturbation on the developmental process. In total, these studies will examine the relationship changing gastric and colonic bacterial population composition with metabolic phenotypes, and provide opportunities for further exploration.

描述（由申请人提供）：在美国和其他发达国家，肥胖的发生率一直在迅速增加。我们的假设是，由于包括抗生素暴露在内的现代化，在古代起源的土著微生物种群中发生了变化。我们的假设是，微生物组组成中的这些变化至少在肥胖的发生率增加中起作用。更具体地说，我们还假设常见的抗生素治疗偶然会导致代谢活性胃肠道细菌种群的组成变化，并且该作用可能是顺序的，在下一代中，孕产妇的变化然后遗传为下一代。我们将通过研究与胃皮细胞相互作用的主要胃细菌的结肠微生物群和幽门螺杆菌的幽门螺杆菌来检验这一假设，这些胃上皮相互作用，该胃上皮产生与能量稳态有关的激素（瘦素和生长素蛋白）。我们提出了5项研究。研究A1将是评估母亲幽门螺杆菌状况在荷兰目前入学的队列中儿童肥胖的发展的关联。研究A2将检查幽门螺杆菌状况和胃激素，炎症和免疫力的生理学的儿童之间的关系。研究A3将评估由于临床表明幽门螺杆菌的临床表明，年轻人的激素和代谢表型的变化。研究B1将根据代谢和激素表型评估对低抗生素剂量连续给药的幼鼠的影响。研究B2将研究单例和双胞胎生命第一年的肠道菌群的发展，并将评估抗生素扰动对发育过程的影响。总的来说，这些研究将研究改变胃和结肠细菌种群组成与代谢表型的关系，并为进一步探索提供机会。