title: Helicobacter pylori colonization ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism.
abstract: BACKGROUND
  There is an inverse secular trend between the incidence of obesity and gastric colonization with Helicobacter pylori, a bacterium that can affect the secretion of gastric hormones that relate to energy homeostasis. H. pylori strains that carry the cag pathogenicity island (PAI) interact more intimately with gastric epithelial cells and trigger more extensive host responses than cag(-) strains. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes.
  
  
  RESULTS
  To test this hypothesis, we examined metabolic and inflammatory markers in db/db mice and mice with diet-induced obesity experimentally infected with isogenic forms of H. pylori strain 26695: the cag PAI wild-type and its cag PAI mutant strain 99-305. H. pylori colonization decreased fasting blood glucose levels, increased levels of leptin, improved glucose tolerance, and suppressed weight gain. A response found in both wild-type and mutant H. pylori strain-infected mice included decreased white adipose tissue macrophages (ATM) and increased adipose tissue regulatory T cells (Treg) cells. Gene expression analyses demonstrated upregulation of gastric PPAR γ-responsive genes (i.e., CD36 and FABP4) in H. pylori-infected mice. The loss of PPAR γ in immune and epithelial cells in mice impaired the ability of H. pylori to favorably modulate glucose homeostasis and ATM infiltration during high fat feeding.
  
  
  CONCLUSIONS
  Gastric infection with some commensal strains of H. pylori ameliorates glucose homeostasis in mice through a PPAR γ-dependent mechanism and modulates macrophage and Treg cell infiltration into the abdominal white adipose tissue.
authors.affiliation: Nutritional Immunology and Molecular Medicine Laboratory, Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia, United States of America. jbassaga@vt.edu
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.forename: Maria Gloria
authors.initials: MG
authors.lastname: Dominguez-Bello
authors.forename: Barbara
authors.initials: B
authors.lastname: Kronsteiner
authors.forename: Adria
authors.initials: A
authors.lastname: Carbo
authors.forename: Pinyi
authors.initials: P
authors.lastname: Lu
authors.forename: Monica
authors.initials: M
authors.lastname: Viladomiu
authors.forename: Mireia
authors.initials: M
authors.lastname: Pedragosa
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Zhang
authors.forename: Bruno W
authors.initials: BW
authors.lastname: Sobral
authors.forename: Shrinivasrao P
authors.initials: SP
authors.lastname: Mane
authors.forename: Saroj K
authors.initials: SK
authors.lastname: Mohapatra
authors.forename: William T
authors.initials: WT
authors.lastname: Horne
authors.forename: Amir J
authors.initials: AJ
authors.lastname: Guri
authors.forename: Michael
authors.initials: M
authors.lastname: Groeschl
authors.forename: Gabriela
authors.initials: G
authors.lastname: Lopez-Velasco
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology; D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D018955:CD36 Antigens / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D020869:Gene Expression Profiling; D044404:Genomic Islands / Q000235:genetics*; D054439:Ghrelin / Q000097:blood; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism*; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development*; D006706:Homeostasis / Q000502:physiology*; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009765:Obesity / Q000382:microbiology*; D047495:PPAR gamma / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D054439:Ghrelin; D007328:Insulin; D020738:Leptin; D047495:PPAR gamma