title: Effect of genetic background and postinfectious stress on visceral sensitivity in Citrobacter rodentium-infected mice.
abstract: Infectious gastroenteritis is a major risk factor to develop postinfectious irritable bowel syndrome (PI-IBS). It remains unknown why only a subgroup of infected individuals develops PI-IBS. We hypothesize that immunogenetic predisposition is an important risk factor. Hence, we studied the effect of Citrobacter rodentium infection on visceral sensitivity in Th1-predominant C57BL/6 and Th2-predominant Balb/c mice.
  
  
  
  Eight-week-old mice were gavaged with C. rodentium, followed by 1 h of water avoidance stress (WAS) at 5 weeks PI. At 10, 14 days, and 5 weeks PI, samples were assessed for histology and inflammatory gene expression by RT-qPCR. Visceral sensitivity was evaluated by visceromotor response recordings (VMR) to colorectal distension.
  
  
  
  Citrobacter rodentium evoked a comparable colonic inflammatory response at 14 days PI characterized by increased crypt length and upregulation of Th1/Th17 cytokine mRNA levels (puncorrected  < 0.05) in both C57BL/6 and Balb/c mice. At 5 weeks PI, inflammatory gene mRNA levels returned to baseline in both strains. The VMR was maximal at 14 days PI in C57BL/6 (150 ± 47%; p = 0.02) and Balb/c mice (243 ± 52%; p = 0.03). At 3 weeks PI, the VMR remained increased in Balb/c (176 ± 23%; p = 0.02), but returned to baseline in C57BL/6 mice. At 5 weeks PI, WAS could not re-introduce visceral hypersensitivity (VHS).
  
  
  
  Citrobacter rodentium infection induces transient VHS in C57BL/6 and Balb/c mice, which persisted 1 week longer in Balb/c mice. Although other strain-related differences may contribute, a Th2 background may represent a risk factor for prolonged PI-VHS. As PI-VHS is transient, other factors are crucial for persistent VHS development as observed in PI-IBS.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: S U
authors.initials: SU
authors.lastname: Mondelaers
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: S A
authors.initials: SA
authors.lastname: Theofanous
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: M V
authors.initials: MV
authors.lastname: Florens
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Perna
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Aguilera-Lizarraga
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: G E
authors.initials: GE
authors.lastname: Boeckxstaens
authors.affiliation: Translational Research Center for Gastrointestinal Disorders, Dept. of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: M M
authors.initials: MM
authors.lastname: Wouters
mesh_terms: D000818:Animals; D044082:Citrobacter rodentium; D004756:Enterobacteriaceae Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000068617:Genetic Background; D055261:Immunogenetic Phenomena / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013312:Stress, Physiological / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology; D059265:Visceral Pain / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators
keywords: Citrobacter rodentium; irritable bowel syndrome; visceral hypersensitivity