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.
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.
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.
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.
Supplemental Digital Content is Available in the Text.Article first published online 7 September 2017.
1Department of Clinical Science, University of Bergen, Bergen, Norway;
2Department of Pediatrics, Haukeland University Hospital, Bergen, Norway;
3Department of Transplantation Medicine, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Oslo, Norway;
4K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway;
5Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway;
6Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway;
7Department of Clinical Medicine, University of Bergen, Bergen, Norway;
8Department of Medicine, Haukeland University Hospital, Bergen, Norway;
9National Centre for Ultrasound in Gastroenterology, Department of Medicine, Haukeland University Hospital, Bergen, Norway;
10Department of Gastroenterology, Oslo University Hospital, Ullevål, Oslo, Norway;
11Max Planck Institute for Evolutionary Biology, Plön, Germany;
12Institute for Experimental Medicine, Christian-Albrechts-University of Kiel, Kiel, Germany;
13Department of Transplantation Medicine, Section of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; and
14Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
Address correspondence to: Johannes R. Hov, MD, PhD, Division for Surgery, Inflammatory medicine and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Pb 4950 Nydalen, N-0424 Oslo, Norway (e-mail: firstname.lastname@example.org).
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.ibdjournal.org).
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).
The authors have no conflict of interest to disclose.
Received April 29, 2017
Accepted July 11, 2017