Helicobacter typhlonius and Helicobacter rodentium differentially affect the severity of colon inflammation and inflammation-associated neoplasia in IL10-deficient mice.
Infection with Helicobacter species is endemic in many animal facilities and may alter the penetrance of inflammatory bowel disease (IBD) phenotypes. However, little is known about the relative pathogenicity of H. typhlonius, H. rodentium, and combined infection in IBD models. We infected adult and neonatal IL10-/- mice with H. typhlonius, H. rodentium, or both bacteria. The severity of IBD and incidence of inflammation-associated colonic neoplasia were assessed in the presence and absence of antiHelicobacter therapy. Infected IL10-/- mice developed IBD with severity of noninfected (minimal to no inflammation) < H. rodentium < H. typhlonius <mixed H. rodentium + H. typhlonius (severe inflammation). Inflammation-associated colonic neoplasia was common in infected mice and its incidence correlated with IBD severity. Combined treatment with amoxicillin, clarithromycin, metronidazole, and omeprazole eradicated Helicobacter in infected mice and ameliorated established IBD in both infected and noninfected mice. Infection of IL10-/- mice with H. rodentium, H. typhlonius, or both organisms can trigger development of severe IBD that eventually leads to colonic neoplasia. The high incidence and multiplicity of neoplastic lesions in infected mice make this model well-suited for future research related to the development and chemoprevention of inflammation-associated colon cancer. The similar antiinflammatory effect of antibiotic therapy in Helicobacter-infected and -noninfected IL10-/- mice with colitis indicates that unidentified microbiota in addition to Helicobacter drive the inflammatory process in this model. This finding suggests a complex role for both Helicobacter and other intestinal microbiota in the onset and perpetuation of IBD in these susceptible hosts.
Chichlowski
Maciej
M
Department of Pathology, Duke University, Durham, North Carolina, USA.
Sharp
Julie M
JM
Vanderford
Deborah A
DA
Myles
Matthew H
MH
Hale
Laura P
LP
D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000209:etiology* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D016998:Helicobacter / Q000145:classification / Q000472:pathogenicity*; D016481:Helicobacter Infections / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013045:Species Specificity
D000900:Anti-Bacterial Agents; D016753:Interleukin-10