Helicobacter bilis Colonization Enhances Susceptibility to Typhlocolitis Following an Inflammatory Trigger

Abstract

These results indicate that prior colonization with H. bilis heightens the host's sensitivity to enteric inflammation by altering mucosal homeostasis and initiating immune cell activation and migration.

Microbiota and reproducibility of rodent models

“…However, mono-association of germfree IL-10-deficient mice with H. hepaticus results in no intestinal inflammation 56 . This, as well as studies using mice harboring defined microbiota, has led to the belief that some bacteria, such as the rodent helicobacters, do not directly initiate inflammation, but rather serve as provocateurs for inflammation initiated against other microbial species 57–60 .…”

Helicobacter bilis Infection Alters Mucosal Bacteria and Modulates Colitis Development in Defined Microbiota Mice

“…These data documenting the changes in the spatial distribution of the ASF lend support to earlier observations from our laboratory 14, 15 regarding the induction of adaptive responses directed against the resident bacteria following H. bilis infection; namely, that up-regulated antibody and pro-inflammatory cytokine production occurs against select ASF members, including ASF457, ASF356, ASF492, ASF500, and ASF502. Moreover, H. bilis colonization of ASF mice has been shown to significantly increase the expression of mucosal genes associated with lymphocyte activation and inflammatory cell infiltration into the colonic mucosa 13 . It is also possible that host responses to ASF457 and H. bilis relate to their mobility (i.e., flagellated bacteria) and their tendency to make their way into the mucosa where they may more easily interact with various components (e.g., dendritic cells) of the mucosal immune system.…”

“…An immunocompetent mouse model colonized with a more complex yet defined microbiota would be helpful in understanding host-microbiota interactions that elicit IBD. We have previously used Helicobacter bilis infection in defined microbiota C3H/HeN mice to investigate microbial modulation of IBD 12, 13 . A defined microbiota, the altered Schaedler flora (ASF), consisting of eight murine bacterial species, served as the model bacterial community.…”

Systemic Macrophage Depletion Inhibits Helicobacter bilis-Induced Proinflammatory Cytokine-Mediated Typhlocolitis and Impairs Bacterial Colonization Dynamics in a BALB/c Rag2 −/− Mouse Model of Inflammatory Bowel Disease

“…In immunocompetent mice (C3H) mice with defined microbiota, H. bilis infection-even in the absence of overt colitis-results in a significant increase in the expression pattern of a plethora of mucosal genes, including those involved in lymphocyte activation (e.g., Cd28 and Tnfsf13b) and regulation (e.g., Il-17a) and in inflammatory cell chemotaxis (e.g., Itgb2, Ccl8, and Ccr5) (27). Importantly, H. bilis can cause the exacerbation of DSS-induced colitis, as shown in a study using C3H/HeN:TAC mice colonized with defined microflora (28). Recent studies in our laboratory performed in C57BL/6 mice have highlighted the role of EHS, H. bilis, H. muridarum, and H. hepaticus in immunomodulating the pathogenesis of H. pylori via a Th17 regulatory pathway (18,26).…”

“…In IBD, macrophages within the inflamed mucosa are derived from mainly circulating macrophages and, upon stimulation, secrete various proinflammatory cytokines, such as interleukin-1 (IL-1), IL-6, IL-8, IL-12, IL-18, and tumor necrosis factor alpha (TNF-␣), all of which can mediate the associated pathology (41,53). Macrophages and other phagocytes, primarily DCs and neutrophils, mediate the release of reactive oxygen species, including myeloperoxidase (MPO) (predominantly from neutrophils) and nitric oxide (from macrophages), with purported direct epithelial injury and a battery of subcellular and molecular damage to DNA, RNA, protein, lipids, and metabolites in IBD and colon cancer in humans and animal models (2,7,21,28,33,48).…”