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Review
. 2015 Nov 19:6:555.
doi: 10.3389/fimmu.2015.00555. eCollection 2015.

Mechanisms of Microbe-Host Interaction in Crohn's Disease: Dysbiosis vs. Pathobiont Selection

Ludovica F Buttó  1 , Monika Schaubeck  1 , Dirk Haller  1
Affiliations
Review

Mechanisms of Microbe-Host Interaction in Crohn's Disease: Dysbiosis vs. Pathobiont Selection

Ludovica F Buttó et al. Front Immunol. .

Abstract

Crohn's disease (CD) is a systemic chronic inflammatory condition mainly characterized by discontinuous transmural pathology of the gastrointestinal tract and frequent extraintestinal manifestations with intermittent episodes of remission and relapse. Genome-wide association studies identified a number of risk loci that, catalyzed by environmental triggers, result in the loss of tolerance toward commensal bacteria based on dysregulated innate effector functions and antimicrobial defense, leading to exacerbated adaptive immune responses responsible for chronic immune-mediated tissue damage. In this review, we discuss the inter-related role of changes in the intestinal microbiota, epithelial barrier integrity, and immune cell functions on the pathogenesis of CD, describing the current approaches available to investigate the molecular mechanisms underlying the disease. Substantial effort has been dedicated to define disease-associated changes in the intestinal microbiota (dysbiosis) and to link pathobionts to the etiology of inflammatory bowel diseases. A cogent definition of dysbiosis is lacking, as well as an agreement of whether pathobionts or complex shifts in the microbiota trigger inflammation in the host. Among the rarely available animal models, SAMP/Yit and TNF(deltaARE) mice are the best known displaying a transmural CD-like phenotype. New hypothesis-driven mouse models, e.g., epithelial-specific Caspase8(-/-), ATG16L1(-/-), and XBP1(-/-) mice, validate pathway-focused function of specific CD-associated risk genes highlighting the role of Paneth cells in antimicrobial defense. To study the causal role of bacteria in initiating inflammation in the host, the use of germ-free mouse models is indispensable. Unraveling the interactions of genes, immune cells and microbes constitute a criterion for the development of safe, reliable, and effective treatment options for CD.

Keywords: Crohn’s disease; IBD; IEC; Paneth cells; TNF; barrier dysfunction; dysbiosis; microbiota.

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Figures

Figure 1
Figure 1
The different influencing factors and characteristics of dysbiosis. The intestinal microbiota is influenced in diversity, composition, function, and prevalence of pathobionts by internal and external factors. Consequently, the microbiota varies in immune relevant characteristics and thereby shifting from a eubiotic to a dysbiotic state.
See this image and copyright information in PMC

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