Disappearing gastrointestinal microbiota in epidemic obesity.

Summary

Principal Investigator: M J Blaser
Affiliation: New York University
Country: USA
Abstract: 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. PUBLIC HEALTH RELEVANCE: 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.
Funding Period: ----------------2010 - ---------------2015-
more information: NIH RePORT

Top Publications

  1. pmc A brave new world: the lung microbiota in an era of change
    Leopoldo N Segal
    1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University Human Microbiome Program, New York University School of Medicine, New York, New York
    Ann Am Thorac Soc 11:S21-7. 2014
  2. pmc Antibiotic exposure and the development of coeliac disease: a nationwide case-control study
    Karl Mårild
    Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
    BMC Gastroenterol 13:109. 2013
  3. ncbi Candida krusei colonization in patients with gastrointestinal diseases
    Duong Thu Huong
    Institute of Biotechnology, Vietnam Academy of Sciences and Technology, Viet Nam
    Med Mycol 51:884-7. 2013
  4. pmc Ethnicity is a strong predictor for Helicobacter pylori infection in young women in a multi-ethnic European city
    Wouter J den Hollander
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
    J Gastroenterol Hepatol 28:1705-11. 2013
  5. pmc Pathways in microbe-induced obesity
    Laura M Cox
    Department of Microbiology, New York University Sackler Institute of Graduate Biomedical Sciences, New York, NY 10016, USA
    Cell Metab 17:883-94. 2013
  6. ncbi Association of caesarean delivery with child adiposity from age 6 weeks to 15 years
    J Blustein
    Department of Health Policy, Medicine, and Population Health, NYU School of Medicine, New York, NY 10012, USA
    Int J Obes (Lond) 37:900-6. 2013
  7. pmc Association between Helicobacter pylori and mortality in the NHANES III study
    Yu Chen
    Department of Population Health, New York University School of Medicine, New York, NY 10016, USA
    Gut 62:1262-9. 2013
  8. pmc Antibiotics in early life alter the murine colonic microbiome and adiposity
    Ilseung Cho
    Department of Medicine, New York University School of Medicine, New York, New York 10016, USA
    Nature 488:621-6. 2012
  9. pmc Infant antibiotic exposures and early-life body mass
    L Trasande
    Department of Pediatrics, New York University School of Medicine, New York, NY 10016, USA
    Int J Obes (Lond) 37:16-23. 2013
  10. pmc Distinct cutaneous bacterial assemblages in a sampling of South American Amerindians and US residents
    Martin J Blaser
    Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA
    ISME J 7:85-95. 2013

Scientific Experts

  • F Francois
  • Yu Chen
  • Ingrid Lisanne Holster
  • Claudia S Plottel
  • Ilseung Cho
  • Martin J Blaser
  • L Trasande
  • J Blustein
  • Caroline M den Hoed
  • Leopoldo N Segal
  • Wouter J den Hollander
  • Karl Mårild
  • M J Blaser
  • Laura M Cox
  • Duong Thu Huong
  • L M Cox
  • M Liu
  • Guillermo I Perez-Perez
  • Albert Hofman
  • Glida Hidalgo
  • Frances van Deurzen
  • T Attina
  • Vincent W Jaddoe
  • Isidoro Estrada
  • Nguyen Thi Thanh Binh
  • Nguyen Van Thinh
  • David S Perlin
  • A M Ryan
  • Benjamin Lebwohl
  • Rob Knight
  • Yanan Zhao
  • Maria G Dominguez-Bello
  • Elizabeth K Costello
  • E Corwin
  • Nguyen Thi Hong Hanh
  • Jonas F Ludvigsson
  • Ta Thi Loan
  • Anneke J van Vuuren
  • Ernst J Kuipers
  • Jose C Clemente
  • Monica Contreras
  • Weimin Ye
  • Tim Card
  • Magda Magris
  • Zhan Gao
  • Henriette A Moll
  • Guillermo I Perez Perez
  • Nguyen Thi Nguyet
  • Peter H R Green
  • Anne J Vila
  • Johan C de Jongste
  • Ernest J Kuipers

Detail Information

Publications18

  1. pmc A brave new world: the lung microbiota in an era of change
    Leopoldo N Segal
    1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, New York University Human Microbiome Program, New York University School of Medicine, New York, New York
    Ann Am Thorac Soc 11:S21-7. 2014
    ..Animal models show that antibiotic exposure in early life has developmental consequences. Considering the potential effects of this altered microbiome on pulmonary responses will be critical for future investigations. ..
  2. pmc Antibiotic exposure and the development of coeliac disease: a nationwide case-control study
    Karl Mårild
    Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
    BMC Gastroenterol 13:109. 2013
    ..Although antibiotics are common environmental factors with a profound impact on intestinal microbiota, data on antibiotic use as a risk factor for subsequent CD development are scarce...
  3. ncbi Candida krusei colonization in patients with gastrointestinal diseases
    Duong Thu Huong
    Institute of Biotechnology, Vietnam Academy of Sciences and Technology, Viet Nam
    Med Mycol 51:884-7. 2013
    ..pylori infection rates were 82%, 35% and 30%, respectively, for the same groups of patients. C. krusei was not detected in stomach samples from normal controls...
  4. pmc Ethnicity is a strong predictor for Helicobacter pylori infection in young women in a multi-ethnic European city
    Wouter J den Hollander
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
    J Gastroenterol Hepatol 28:1705-11. 2013
    ..pylori-related diseases. We aimed to define H. pylori prevalence as well as risk groups for H. pylori in a cohort of young women living in a multi-ethnic European city...
  5. pmc Pathways in microbe-induced obesity
    Laura M Cox
    Department of Microbiology, New York University Sackler Institute of Graduate Biomedical Sciences, New York, NY 10016, USA
    Cell Metab 17:883-94. 2013
    ..Model physiologic systems and perturbations including gastric bypass surgery, pregnancy, and hibernation provide insight into the respective roles of the critical participants...
  6. ncbi Association of caesarean delivery with child adiposity from age 6 weeks to 15 years
    J Blustein
    Department of Health Policy, Medicine, and Population Health, NYU School of Medicine, New York, NY 10012, USA
    Int J Obes (Lond) 37:900-6. 2013
    ..o assess associations of caesarean section with body mass from birth through adolescence...
  7. pmc Association between Helicobacter pylori and mortality in the NHANES III study
    Yu Chen
    Department of Population Health, New York University School of Medicine, New York, NY 10016, USA
    Gut 62:1262-9. 2013
    ..Thus, it is important to evaluate its influence on total and category-specific mortality...
  8. pmc Antibiotics in early life alter the murine colonic microbiome and adiposity
    Ilseung Cho
    Department of Medicine, New York University School of Medicine, New York, New York 10016, USA
    Nature 488:621-6. 2012
    ..In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation...
  9. pmc Infant antibiotic exposures and early-life body mass
    L Trasande
    Department of Pediatrics, New York University School of Medicine, New York, NY 10016, USA
    Int J Obes (Lond) 37:16-23. 2013
    ..To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life...
  10. pmc Distinct cutaneous bacterial assemblages in a sampling of South American Amerindians and US residents
    Martin J Blaser
    Department of Medicine, New York University Langone Medical Center, New York, NY 10016, USA
    ISME J 7:85-95. 2013
    ..The results provide evidence that ethnicity, lifestyle and/or geography are associated with the structure of human cutaneous bacterial communities...
  11. pmc The impact of Helicobacter pylori on atopic disorders in childhood
    I Lisanne Holster
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Centre, Rotterdam, The Netherlands
    Helicobacter 17:232-7. 2012
    ..Some studies have reported a negative association between H. pylori and asthma and allergy, but data are inconsistent and there are a few studies in children...
  12. pmc Association between gastric Helicobacter pylori colonization and glycated hemoglobin levels
    Yu Chen
    Department of Environmental Medicine, New York University School of Medicine, New York, NY, USA
    J Infect Dis 205:1195-202. 2012
    ..Few studies have evaluated the potential influence of Helicobacter pylori on biomarkers for diabetes...
  13. pmc The human microbiome: at the interface of health and disease
    Ilseung Cho
    Department of Medicine, NYU Langone Medical Center, New York, New York 10016, USA
    Nat Rev Genet 13:260-70. 2012
    ..Both the microbiome and metagenome probably have important functions in health and disease; their exploration is a frontier in human genetics...
  14. pmc Microbiome and malignancy
    Claudia S Plottel
    Department of Medicine, New York University Langone Medical Center, New York University, New York, NY 10016, USA
    Cell Host Microbe 10:324-35. 2011
    ..These are separate facets of a complex biology interfacing all the microbial species we harbor from birth onward toward early reproductive success and eventual senescence...
  15. pmc Helicobacter pylori and the birth cohort effect: evidence for stabilized colonization rates in childhood
    Caroline M den Hoed
    Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
    Helicobacter 16:405-9. 2011
    ..pylori prevalence in 6- to 8-year-old Dutch children from 19% in 1978 to 9% in 1993. Knowledge about birth-cohort-related H. pylori prevalence is relevant as a predictor for the future incidence of H. pylori-associated conditions...
  16. pmc The effect of H. pylori eradication on meal-associated changes in plasma ghrelin and leptin
    Fritz Francois
    New York University Langone Medical Center, New York, NY, USA
    BMC Gastroenterol 11:37. 2011
    ..pylori colonization. We prospectively evaluated the effect of H. pylori eradication on meal-associated changes in serum ghrelin and leptin levels, and body weight...