Rapid Onset of Ulcerative Typhlocolitis in B6.129P2-IL10 tm1Cgn (IL-10 −/− ) Mice Infected with Helicobacter trogontum Is Associated with Decreased Colonization by Altered Schaedler's Flora

Abstract

Infection with Helicobacter trogontum , a urease-positive helicobacter isolated from subclinically infected rats, was evaluated in B6.129P2-IL10 ^tm1Cgn (interleukin-10 ^−/− [IL-10 ^−/− ]) and C57BL/6 (B6) mice. In a first experiment, IL-10 ^−/− mice naturally infected with Helicobacter rodentium had subclinical typhlocolitis but developed severe diarrhea and loss of body condition with erosive to ulcerative typhlocolitis within 1 to 3 weeks of experimental infection with H. trogontum . A second experiment demonstrated that helicobacter-free IL-10 ^−/− mice dosed with H. trogontum also developed severe clinical signs and typhlocolitis within 2 to 4 weeks, whereas B6 mice colonized with H. trogontum were resistant to disease. In a third experiment, using helicobacter-free IL-10 ^−/− mice, dosing with H. trogontum resulted in acute morbidity and typhlocolitis within 8 days. Acute typhlocolitis was accompanied by signs of sepsis supported by degenerative hemograms and recovery of Escherichia coli and Proteus spp. from the livers of infected mice. Quantitative PCR data revealed that H. rodentium and H. trogontum may compete for colonization of the lower bowel, as H. trogontum established higher colonization levels in the absence of H. rodentium ( P < 0.003). H. trogontum -induced typhlocolitis was also associated with a significant decrease in the levels of colonization by five of eight anaerobes that comprise altered Schaedler's flora ( P < 0.002). These results demonstrate for the first time that H. rodentium infection in IL-10 ^−/− mice causes subclinical typhlocolitis and that infection with H. trogontum (with or without H. rodentium ) induces a rapid-onset, erosive to ulcerative typhlocolitis which impacts the normal anaerobic flora of the colon and increases the risk of sepsis.