Characterizing the pathogenic potential and virulent mechanisms of Helicobacter saguini to cause inflammatory bowel disease and colon cancer

Abstract

Inflammatory bowel disease (IBD) is an idiopathic, chronic inflammatory disease that causes severe tissue damage to the gastrointestinal tract. The etiology is hypothesized to arise from multifactorial contributions in genetic predispositions, environmental factors, and the intestinal microbiome that destroys epithelial barrier integrity and allows chronic, unregulated immune responses to intestinal bacteria. Family history is the strongest risk for developing IBD, representing shared genetic and environmental factors, including the microbiome. Current pharmacology for IBD is restricted to non-specific anti-inflammatory agents that are limited by serious potential side effects and do not address the root cause(s) of disease. Cotton top tamarins (CTTs) are an endangered primate species highly susceptible to multi-generational, idiopathic IBD and considered the best animal model of human IBD. In 1999, a novel enterohepatic Helicobacter species (EHS), H. saguini, was isolated from cotton top tamarins with IBD. Helicobacter species are spiral-shaped, gram-negative bacteria that colonize the gastrointestinal tracts of mammals, birds, and reptiles and in some instances are associated with inflammatory gastrointestinal pathologies and cancers in their hosts. The discovery of H. saguini in CTTs raised the hypothesis that this bacterium influences the onset of IBD in these primates. Given the endangered status of CTTs, this hypothesis was test alternatively using IL-10-/- mice, a transgenic line susceptible to IBD. C57/129 specific-pathogen-free (SPF) IL-10-/- mice dosed orally inoculated were not colonized with H. saguini; however, H. saguini mono-associated infection in C57/129 germfree IL-10-/- mice developed IBD.