1. Gut Microbiota: Mining for Therapeutic Potential
Ann M. O’Hara, Fergus Shanahan 
Clinical Gastroenterology and Hepatology 
Volume 5, Issue 3, Pages (March 2007)
DOI: /j.cgh
Copyright © 2007 AGA Institute Terms and Conditions

2. Figure 1
Changes in intestinal structure and function in germ-free animals compared with colonized animals raised under conventional conditions. Reconstitution of germ-free mice with a microbiota restores the mucosal immune system, and commensal bacteria exert numerous protective, structural, and metabolic effects on the intestinal epithelium.
Clinical Gastroenterology and Hepatology 2007 5, DOI: ( /j.cgh )
Copyright © 2007 AGA Institute Terms and Conditions

3. Figure 2
Possible mechanisms contributing to the association of mutations in the CARD15 gene with Crohn’s disease. CARD15 encodes the NOD protein, NOD2, which is expressed in the cytosol of cells of the macrophage/monocyte lineage, DCs, and enterocytes. Stimulation of NOD2 by MDP of bacterial peptidoglycan leads to the activation of the transcription factor NF-κB, and peptidoglycan can signal also to antigen-presenting cells through TLR2. (A) In normal mucosa, TLR2-driven activation of NF-κB is negatively regulated by non-mutated NOD2, thereby preventing excessive production of the proinflammatory Th1 cytokines IL-12 and IFN-γ. Conversely, in NOD2-deficient cells, IL-10 secretion is decreased, and Th1-cell–mediated inflammation occurs through IL-12 as a result of NOD2 to negatively regulate TLR2 signaling. (B) Alternatively, it has been postulated that in antigen-presenting cells expressing mutated NOD2, MDP elevates NF-κB activation and results in excessive IL-1β production and uncontrolled apoptosis, which together might mediate the pathogenesis of Crohn’s disease. (C) Deficient expression of NOD2 by intestinal enterocytes, particularly by Paneth’s cells at the base of the small intestinal crypts, results in decreased secretion of antimicrobial peptides known as α-defensins. Impaired NOD-2–dependent α-defensin production might lead to increased bacterial colonization and a type of bacterial overgrowth that triggers an immunologic response to the microbiota.
Clinical Gastroenterology and Hepatology 2007 5, DOI: ( /j.cgh )
Copyright © 2007 AGA Institute Terms and Conditions