Abstract
BackgroundThere 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.Methodology/Principal FindingsTo 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/SignificanceGastric 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.
Highlights
Helicobacter pylori is the dominant member of the gastric microbiota and has persistently colonized the stomach in humans since our early evolution [1]
We examined the effects of gastric H. pylori infection on appetite-controlling hormones and peroxisome proliferator-activated receptor c (PPAR c), a nuclear receptor and transcription factor that acts as an important thermostat for inflammation and metabolism
The realtime qRT-PCR and ELISA results indicate that gastric leptin mRNA and plasma leptin protein concentrations were higher in the H. pylori-colonized mice, regardless of the cag pathogenicity island (PAI) status, in comparison to the non-colonized group (Table 1)
Summary
Helicobacter pylori is the dominant member of the gastric microbiota and has persistently colonized the stomach in humans since our early evolution [1]. There is increasing evidence of H. pylori protection against esophageal and cardial pathologies [2,7,8,9], childhood asthma [10,11,12] and childhood allergies [11,13]. The mechanisms underlying this protective effect of H. pylori acting as a commensal bacterium are largely unknown, for asthma the suppression of T helper 2 responses by a neutrophil-activating protein of H. pylori favorably modulates allergic asthma in mice [14]. We hypothesized that gastric colonization with H. pylori strains differing in cag PAI status exert distinct effects on metabolic and inflammatory phenotypes
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