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

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，肥胖症的发病率正在迅速增加。我们的假设是，由于现代化（包括抗生素暴露），古老起源的本土微生物种群正在发生变化。我们的假设是，微生物组组成的这些变化至少在一定程度上导致了肥胖发病率的增加。更具体地说，我们还假设常见的抗生素治疗偶然会引起代谢活跃的胃肠道细菌种群组成的变化，并且这种影响可能是连续的，其中母体的变化然后被下一代遗传。我们将通过研究结肠微生物群和幽门螺杆菌来检验这一假设，幽门螺杆菌是与胃上皮相互作用的主要胃细菌，胃上皮产生参与能量稳态的激素（瘦素和生长素释放肽）。我们提出了 5 项研究。研究 A1 将在荷兰目前入组的队列中评估母亲幽门螺杆菌状况与儿童肥胖发展的关系。研究 A2 将检查儿童中幽门螺杆菌状态与胃激素、炎症和免疫生理学的关系。研究 A3 将评估因临床指示根除幽门螺杆菌而引起的年轻人激素和代谢表型的变化。研究 B1 将评估持续施用低剂量抗生素对年轻小鼠代谢和激素表型的影响。研究 B2 将检查单胎和双胞胎出生后第一年肠道微生物群的发育，并将评估抗生素扰动对发育过程的影响。总的来说，这些研究将探讨胃和结肠细菌种群组成的变化与代谢表型的关系，并为进一步探索提供机会。