Guanylate Cyclase C Activation Shapes the Intestinal Microbiota in Patients with Familial Diarrhea and Increased Susceptibility for Crohn's Disease. Issue 10 (October 2017)

• Record Type: Journal Article
• Authors: Tronstad, Rune R.; Kummen, Martin; Holm, Kristian; von Volkmann, Hilde L.; Anmarkrud, Jarl A.; Høivik, Marte L.; Moum, Bjørn; Gilja, Odd H.; Hausken, Trygve; Baines, John; Karlsen, Tom H.; Fiskerstrand, Torunn; Hov, Johannes R.
• Is Part Of: Inflammatory bowel diseases. Volume 23:Issue 10(2017)
• Publication Date: 2017-10
• Subjects: Crohn's disease -- guanylate cyclase C -- intestinal microbiota; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000001264
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD. Methods: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives. Results: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS. Conclusions: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS. Abstract : Supplemental Digital Content is Available in the Text.Article first published online 7 September 2017.