Disappearing gastrointestinal microbiota in epidemic obesity.

描述（由申请人提供）：肥胖症的发病率在美国和其他发达国家迅速增加。我们的假设是，由于现代化，包括抗生素暴露，古老起源的土著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对肥胖发病率的增加起到了作用。更具体地说，我们还假设，常见的抗生素治疗是偶然引起的变化，在代谢活跃的胃肠道细菌种群的组成，以及影响可能是连续的，其中母体的变化，然后由下一代继承。我们将通过研究结肠微生物群和幽门螺杆菌来验证这一假设，幽门螺杆菌是与胃上皮相互作用的主要胃细菌，它产生参与能量稳态的激素（瘦素和生长激素释放肽）。我们提出了5项研究。研究A1将评估母体H.幽门螺杆菌状态对儿童肥胖症发展的影响。研究A2将研究H.幽门螺杆菌状态和胃激素、炎症和免疫的生理学。研究A3将评估年轻成人中由于临床指征H根除而引起的激素和代谢表型变化。幽门。研究B1将评估低剂量抗生素连续给药对幼龄小鼠代谢和激素表型的影响。研究B2将检查单胞胎和双胞胎出生后第一年肠道微生物群的发育情况，并评估抗生素干扰对发育过程的影响。总之，这些研究将研究胃和结肠细菌种群组成变化与代谢表型的关系，并为进一步探索提供机会。

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.