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.

Salmonella SPI-1-mediated neutrophil recruitment during enteric colitis is associated with reduction and alteration in intestinal microbiota

“…13,23 Previously published results on the effect of enteric infections on the microbiota have indicated that infection-associated inflammation acts to extensively modify and reduce indigenous microbes. 2,3,18 We sought to evaluate the effect of infection with the three S. typhimurium strains on the total numbers and composition of the murine intestinal microbiota. We found that while inflammatory changes associated with WT infection, induced extensive perturbations in the murine microbiota (as previously described in both the LD 13 and the HD models 2 ), inflammation induced during infection with invAmut strain failed to affect the host microbiota in the same way (Figs.…”

“…2), as previous microbiota studies in infectious colitis linked development of intestinal inflammation to microbiota perturbations. 2,3,18 Infection with WT S. typhimurium resulted in a significant decrease in total cecal bacterial numbers, as assessed by SYBR green staining, starting at day 3 p.i. (Fig.…”

The Family Helicobacteraceae

“…Some examples of these models are described in the following reports and reviews (Franklin et al 2001;Jiang et al 2001;Whary et al 2006;Hale et al 2007;Chichlowski et al 2008;Nell et al 2010;Patterson et al 2010;Eaton et al 2011;Fox et al 2011;Hansen et al 2011). …”

Cytolethal Distending Toxin PromotesHelicobacter cinaedi-Associated Typhlocolitis in Interleukin-10-Deficient Mice

“…It has been reported that Helicobacter bilis, Helicobacter hepaticus, Helicobacter typhlonius, and Helicobacter trogontum persistently colonize the lower bowel of mice and induce proliferative typhlocolitis in immune-dysregulated mice, including IL-10 Ϫ/Ϫ mice (14,26,30,31,34,54). In this study, we used the IL-10 Ϫ/Ϫ mouse model to evaluate the pathogenic potential of H. cinaedi and the role of CDT in inducing gastrointestinal disease.…”