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  Guanylate cyclase C activation shapes the intestinal microbiota in patients with familial diarrhea and increased susceptibility for Crohn's Disease

Tronstad, R. R., Kummen, M., Holm, K., von Volkmann, H. L., Anmarkrud, J. A., Høivik, M. L., et al. (2017). Guanylate cyclase C activation shapes the intestinal microbiota in patients with familial diarrhea and increased susceptibility for Crohn's Disease. Inflammatory Bowel Diseases, 23(10), 1752-1761. doi:10.1097/mib.0000000000001264.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-8BD9-2 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-8BDA-F
Genre: Journal Article

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 Creators:
Tronstad, Rune R., Author
Kummen, Martin, Author
Holm, Kristian, Author
von Volkmann, Hilde L., Author
Anmarkrud, Jarl A., Author
Høivik, Marte L., Author
Moum, Bjørn, Author
Gilja, Odd H., Author
Hausken, Trygve, Author
Baines, John F.1, Author              
Karlsen, Tom H., Author
Fiskerstrand, Torunn, Author
Hov, Johannes R., Author
Affiliations:
1Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445638              

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Free keywords: Crohn's disease; guanylate cyclase C; intestinal microbiota; inflammatory-bowel-disease; gut microbiota; colitis; genome; index; association; modulation; diversity; pathogen; bacteria; Gastroenterology & Hepatology
 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.

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Language(s): eng - English
 Dates: 2017-04-292017-07-112017-09-072017-10
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1097/mib.0000000000001264
 Degree: -

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Project name : Supported by the Regional Health Authority of Western Norway (Grant No. 911763 to RRT, No. 911802 to THK, and No. 911796 to TF), by the Norwegian Research Council (Grant No. 240787/F20 to JRH), and by the Regional Health Authority of South-Eastern Norway (Grant No. 2016067 to MK)
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Title: Inflammatory Bowel Diseases
  Other : Inflamm. Bowel Dis.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York, NY : Raven Press
Pages: - Volume / Issue: 23 (10) Sequence Number: - Start / End Page: 1752 - 1761 Identifier: ISSN: 1078-0998
CoNE: /journals/resource/954925606820