title: Bugs, genes, fatty acids, and serotonin: Unraveling inflammatory bowel disease?
abstract: The annual incidence of the inflammatory bowel diseases (IBDs) ulcerative colitis and Crohn's disease has increased at an alarming rate. Although the specific pathophysiology underlying IBD continues to be elusive, it is hypothesized that IBD results from an aberrant and persistent immune response directed against microbes or their products in the gut, facilitated by the genetic susceptibility of the host and intrinsic alterations in mucosal barrier function. In this review, we will describe advances in the understanding of how the interaction of host genetics and the intestinal microbiome contribute to the pathogenesis of IBD, with a focus on bacterial metabolites such as short chain fatty acids (SCFAs) as possible key signaling molecules.  In particular, we will describe alterations of the intestinal microbiota in IBD, focusing on how genetic loci affect the gut microbial phylogenetic distribution and the production of their major microbial metabolic product, SCFAs. We then describe how enteroendocrine cells and myenteric nerves express SCFA receptors that integrate networks such as the cholinergic and serotonergic neural systems and the glucagon-like peptide hormonal pathway, to modulate gut inflammation, permeability, and growth as part of an integrated model of IBD pathogenesis.  Through this integrative approach, we hope that novel hypotheses will emerge that will be tested in reductionist, hypothesis-driven studies in order to examine the interrelationship of these systems in the hope of better understanding IBD pathogenesis and to inform novel therapies.
authors: Medical Service, West Los Angeles VAMC, Los Angeles, CA, 90073, USA; Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, 90095, USA; Department of Surgery, David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
authors: Jonathan
authors: J
authors: Kaunitz
authors: Medical Service, West Los Angeles VAMC, Los Angeles, CA, 90073, USA; Department of Medicine, David Geffen School of Medicine, Los Angeles, CA, 90095, USA.
authors: Piyush
authors: P
authors: Nayyar
keywords: IBD; Inflammatory bowel disease; crohn's diseas; ulcertative colitis