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.
The incidence of obesity is rapidly increasing in the United States and other developed countries. We will explore the hypothesis that changes in the composition and activity of the ancient endogenous microbiota of the gastrointestinal tract is playing a role in the development of obesity. We will focus on both maternal and antibiotic effects on the composition of the gastric and colonic bacterial populations, and their metabolic effects.
|Alemán, José O; Bokulich, Nicholas A; Swann, Jonathan R et al. (2018) Fecal microbiota and bile acid interactions with systemic and adipose tissue metabolism in diet-induced weight loss of obese postmenopausal women. J Transl Med 16:244|
|Ward, Tonya L; Dominguez-Bello, Maria Gloria; Heisel, Tim et al. (2018) Development of the Human Mycobiome over the First Month of Life and across Body Sites. mSystems 3:|
|Schulfer, Anjelique F; Battaglia, Thomas; Alvarez, Yelina et al. (2018) Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nat Microbiol 3:234-242|
|Stokholm, Jakob; Blaser, Martin J; Thorsen, Jonathan et al. (2018) Maturation of the gut microbiome and risk of asthma in childhood. Nat Commun 9:141|
|Hu, Jiyuan; Koh, Hyunwook; He, Linchen et al. (2018) A two-stage microbial association mapping framework with advanced FDR control. Microbiome 6:131|
|Koh, Hyunwook; Livanos, Alexandra E; Blaser, Martin J et al. (2018) A highly adaptive microbiome-based association test for survival traits. BMC Genomics 19:210|
|Koh, Hyunwook; Blaser, Martin J; Li, Huilin (2017) A powerful microbiome-based association test and a microbial taxa discovery framework for comprehensive association mapping. Microbiome 5:45|
|Ruiz, Victoria E; Battaglia, Thomas; Kurtz, Zachary D et al. (2017) A single early-in-life macrolide course has lasting effects on murine microbial network topology and immunity. Nat Commun 8:518|
|Liu, Menghan; Koh, Hyunwook; Kurtz, Zachary D et al. (2017) Oxalobacter formigenes-associated host features and microbial community structures examined using the American Gut Project. Microbiome 5:108|
|Segal, Leopoldo N; Clemente, Jose C; Wu, Benjamin G et al. (2017) Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung. Thorax 72:13-22|
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