Beyond Digestion: The Pancreas Shapes Intestinal Microbiota and Immunity  Herbert Tilg, Timon E. Adolph  Cell Metabolism  Volume 25, Issue 3, Pages 495-496 (March 2017) DOI: 10.1016/j.cmet.2017.02.018 Copyright © 2017 Elsevier Inc. Terms and Conditions

Figure 1 Pancreatic-Intestinal Crosstalk (1) The pancreas secretes cathelicidin-related antimicrobial peptides (CRAMPs, red dots). (2) Impaired CRAMP secretion (by timed pancreas-specific deletion of ORAI calcium release-activated calcium modulator 1 or “Orai1”) rendered the intestinal microbiota dysbiotic and resulted in bacterial overgrowth and systemic bacteremia, as demonstrated by Ahuja et al. (2017) in this issue of Cell Metabolism. (3) Pancreatic Orai1 deficiency induced spontaneous intestinal inflammation with CD3+ T cells and was associated with Paneth cell hyperplasia and increased expression of intestinal epithelial antimicrobials. Within 3 weeks, 65% of Orai1-deficient mice on a solid diet died, which could be prevented by oral supplementation of CRAMPs. As such, pancreas-derived antimicrobials may shape the intestinal microbiota and gut immune responses. (4) In turn, short-chain fatty acids (SCFAs) derived from the intestinal microbiota may promote CRAMP expression in pancreatic α/β cells, which modulates pancreatic immune responses in auto-immune diabetes (Sun et al., 2015). Cell Metabolism 2017 25, 495-496DOI: (10.1016/j.cmet.2017.02.018) Copyright © 2017 Elsevier Inc. Terms and Conditions