title: Role of gut-brain axis in persistent abnormal feeding behavior in mice following eradication of Helicobacter pylori infection.
abstract: Bacterial infection can trigger the development of functional GI disease. Here, we investigate the role of the gut-brain axis in gastric dysfunction during and after chronic H. pylori infection. Control and chronically H. pylori-infected Balb/c mice were studied before and 2 mo after bacterial eradication. Gastric motility and emptying were investigated using videofluoroscopy image analysis. Gastric mechanical viscerosensitivity was assessed by cardioautonomic responses to distension. Feeding patterns were recorded by a computer-assisted system. Plasma leptin, ghrelin, and CCK levels were measured using ELISA. IL-1beta, TNF-alpha, proopiomelanocortin (POMC), and neuropeptide Y mRNAs were assessed by in situ hybridizations on frozen brain sections. Gastric inflammation was assessed by histology and immunohistochemistry. As shown previously, H. pylori-infected mice ate more frequently than controls but consumed less food per bout, maintaining normal body weight. Abnormal feeding behavior was accompanied by elevated plasma ghrelin and postprandial CCK, higher TNF-alpha (median eminence), and lower POMC (arcuate nucleus) mRNA. Infected mice displayed delayed gastric emptying and visceral hypersensitivity. Eradication therapy normalized gastric emptying and improved gastric sensitivity but had no effect on eating behavior. This was accompanied by persistently increased TNF-alpha in the brain and gastric CD3(+) T-cell counts. In conclusion, chronic H. pylori infection in mice alters gastric emptying and mechanosensitivity, which improve after bacterial eradication. A feeding pattern reminiscent of early satiety persists after H. pylori eradication and is accompanied by increased TNF-alpha in the brain. The results support a role for altered gut-brain pathways in the maintenance of postinfective gut dysfunction.
authors.affiliation: Intestinal Diseases Research Program, McMaster Univ., MUMC 4W8, Hamilton, Ontario L8N 3Z5. bercikp@mcmaster.ca
authors.forename: Premysl
authors.initials: P
authors.lastname: Bercik
authors.forename: Elena F
authors.initials: EF
authors.lastname: Verdú
authors.forename: Jane A
authors.initials: JA
authors.lastname: Foster
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Angela
authors.initials: A
authors.lastname: Scharringa
authors.forename: Iain
authors.initials: I
authors.lastname: Kean
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Patricia
authors.initials: P
authors.lastname: Blennerhassett
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Collins
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology; D001921:Brain / Q000502:physiology*; D017252:CD3 Complex / Q000502:physiology; D002452:Cell Count; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005756:Gastritis / Q000503:physiopathology / Q000523:psychology; D005769:Gastrointestinal Motility / Q000502:physiology; D041981:Gastrointestinal Tract / Q000502:physiology*; D054439:Ghrelin / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology*; D016480:Helicobacter pylori; D017403:In Situ Hybridization; D020738:Leptin / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D011949:Receptors, Cholecystokinin / Q000502:physiology
chemical_list: D017252:CD3 Complex; D054439:Ghrelin; D020738:Leptin; D011949:Receptors, Cholecystokinin