Phenome of coeliac disease vs. inflammatory bowel disease

Abstract

Coeliac disease (CeD) is characterized by gliadin-induced intestinal inflammation appearing in genetically susceptible individuals, such as HLA-DQ2.5 carriers. CeD, as well as other chronic intestinal disorders, such as Crohn's disease (CD) and ulcerative colitis, has been associated with increased morbidity and mortality, but the causes are unknown. We systematically analysed CeD-associated diagnoses and compared them to conditions enriched in subjects with CD/UC as well as in HLA-DQ2.5 carriers without CeD. We compared the overall and cause-specific mortality and morbidity of 3,001 patients with CeD, 2,020 with CD, 4,399 with UC and 492,200 controls in the community-based UK Biobank. Disease-specific phenotypes were assessed with the multivariable Phenome Wide Association Study (PheWAS) method. Associations were adjusted for age, sex and body mass index. All disease groups displayed higher overall mortality than controls (CD: aHR = 1.91[1.70–2.17]; UC: aHR = 1.32 [1.20–1.46]; CeD: aHR = 1.38 [1.22–1.55]). Cardiovascular and cancer-related deaths were responsible for the majority of fatalities. PheWAS analysis revealed 166 Phecodes overrepresented in all three disorders, whereas only ~ 20% of enriched Phecodes were disease specific. Seven of the 58 identified CeD-specific Phecodes were enriched in individuals homozygous for HLA-DQ2.5 without diagnosed CeD. Four out of these seven Phecodes and eight out of 19 HLA-DQ2.5 specific Phecodes were more common in homozygous HLA-DQ2.5 subjects with vs. without CeD, highlighting the interplay between genetics and diagnosis-related factors. Our study illustrates that the morbidity and mortality in CeD share similarities with CD/UC, while the CeD-restricted conditions might be driven by both inherited and acquired factors.

The Role of CD1 Gene Polymorphism in the Genetic Susceptibility to Spondyloarthropathies in the Moroccan Population and the Possible Cross-Link with Celiac Disease

“…Growing evidence indicates that gut microbiome is involved in the pathogenesis of SpA [ 7 ] and AS patients may have a 5.3-fold higher incidence of chronic inflammatory intestinal diseases such as IBD than healthy individuals [ 30 ]. IBD has a partially shared pathogenesis with CeD; in both conditions, genetics and environment contribute to immune dysregulation, leading to chronic inflammation and disease [ 31 ].…”

The Role of Gluten in Gastrointestinal Disorders: A Review

“…While in the literature there are many studies regarding the correlation between gut microbiota and CD, fewer studies were drafted about gut microflora and NCGS and its possible role in the disease pathogenesis [ 24 , 43 , 44 ]. At baseline, Garcia-Mazcorro et al found an increased number of Actinobacillus and Ruminococcaceae genera in NCGS patients compared to Celiac ones and a higher rates of Pseudomonas spp.…”

“…As we discussed above, gluten might be one of the main players in this interplay due to its role in intestinal inflammation. Indeed, Celiac disease, which is a chronic immune-mediated enteropathy consequent to gluten intake, shares with IBD a multifactorial etiology, resulting from a complex interplay between genetic variability, environmental factors, and dysregulated immune response [ 44 ].…”

User testing to inform modification of the MyHealthyGut digital health application in inflammatory bowel disease

“…MyHealthyGut (MHG) is a mobile app that was originally designed for celiac disease (CeD) self-management [14,15]. At present, the only treatment for CeD is a strict gluten-free (GF) diet [16]. The app was developed to provide guidance, diet and symptom tracking, and information to users, related to the GF diet and CeD.…”

“…diet [16]. 9 Would you find it useful if patients could share information about their diet and health through the app ahead of appointments?…”