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.
Inflamm Bowel Dis. 2017 Oct;23(10):1752-1761. doi: 10.1097/MIB.0000000000001264.
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.
家族性 GUCY2C 腹泻综合征（FGDS）的患病率为 25%，是一种单基因疾病，可能适合研究炎症性肠病（IBD）的起始因素。我们旨在描述 FGDS 患者中激活的 GUCY2C 突变对肠道微生物群的影响，同时控制克罗恩病的状态，并确定这些变化是否与非相关 IBD 患者观察到的变化具有共同特征。
从 FGDS 患者（N=20）、健康亲属（N=11）、非相关健康个体（N=263）和 IBD 对照组（N=46）收集的粪便样本中的细菌 DNA，进行 16S rRNA 基因 V3-V4 区的测序，以确定肠道微生物群组成。从 FGDS 患者及其亲属那里获得食物频率问卷。
与健康对照组相比，FGDS 显示出许多微生物谱系的明显变化，包括肠杆菌科的增加、双歧杆菌和普拉梭菌的减少，但个体内（alpha）多样性不变。普拉梭菌的减少与克罗恩病中通常观察到的情况一致。患者和相关对照组的饮食模式没有显著差异。相关和非相关健康对照组的肠道微生物群也相似，这表明饮食和家族因素不能解释 FGDS 中肠道微生物群的改变。
这些发现支持 GUCY2C 的激活突变创造了一个对微生物群有重大影响的肠道环境，这可能导致 FGDS 患者对 IBD 的易感性增加。
