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Chapter 13 : Role of Commensal Enteric Bacteria in Intestinal Inflammation: Lessons from Animal Models

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Abstract:

This chapter outlines evidence supporting the hypothesis that chronic immune-mediated intestinal inflammation in genetically susceptible hosts is a consequence of overly aggressive cell-mediated immune responses to a subset of commensal luminal bacteria. The most compelling evidence that normal luminal bacteria induce colitis is the fact that in at least 11 separate models of induced or spontaneous intestinal inflammation, no disease occurs in the absence of bacteria (germ free or sterile state). Recent results in several independent gnotobiotic models demonstrate that commensal enteric bacterial species differ in their capacity to induce chronic intestinal inflammation. Chronic intestinal inflammation is mediated by T lymphocytes, based on the absence of experimental colitis in T-cell-deficient hosts, induction of disease by transfer of CD T lymphocytes, and prevention and reversal of chronic inflammation by blockade of products of T cytokines. A key factor in the induction of chronic immune-mediated intestinal inflammation is the loss of tolerance to luminal bacterial antigens in genetically susceptible hosts. Many studies discussed in the chapter support the hypothesis that chronic intestinal inflammation is a consequence of an overly aggressive cell mediated immune response to a subset of the complex resident enteric bacterial population in genetically susceptible hosts. Results in animal models indicate that manipulation of the luminal microflora by antibiotics, probiotics, and prebiotics can treat established disease and prevent recurrent inflammation. These physiologic bacterial manipulations may have additive and perhaps synergistic activities with more widely used immunosuppressive therapies and emerging growth factor treatments.

Citation: Sartor R. 2003. Role of Commensal Enteric Bacteria in Intestinal Inflammation: Lessons from Animal Models, p 223-240. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch13

Key Concept Ranking

Ulcerative Colitis
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Immune Systems
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Crohn's Disease
0.5266177
Major Histocompatibility Complex
0.49653506
Cell-Mediated Immune Response
0.47160944
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Tables

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TABLE 1.

Animal models that do not develop intestinal inflammation in a germfree (sterile) environment

Citation: Sartor R. 2003. Role of Commensal Enteric Bacteria in Intestinal Inflammation: Lessons from Animal Models, p 223-240. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch13
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TABLE 2

Specificity of induction of colitis in gnotobiotic rodent models by defined bacterial species

Citation: Sartor R. 2003. Role of Commensal Enteric Bacteria in Intestinal Inflammation: Lessons from Animal Models, p 223-240. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch13
Generic image for table
TABLE 3

Relative balance of protective versus detrimental commensal enteric bacterial species determines intestinal inflammation versus mucosal homeostasis

Citation: Sartor R. 2003. Role of Commensal Enteric Bacteria in Intestinal Inflammation: Lessons from Animal Models, p 223-240. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch13

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