0000000000342033
AUTHOR
Elena F. Verdu
A48 COLITIS FAVORS THE EXPANSION OF BACTERIA THAT ACTIVATE PAR2 AMPLIFYING INFLAMMATORY RESPONSE
Abstract Background Proteolytic imbalance has been described in patients with inflammatory bowel disease (IBD) and in different models of experimental colitis. Although the proteases reported to be increased are mainly from the host, the role of bacterial proteases has recently emerged, as they can promote inflammation, in part, through activation of Protease-activated receptors (PARs). PAR2 deficient mice are resistant to inflammation and PAR2 activation affects multiple aspects of the tissue response to injury. However, PAR2 communicates with other receptors such as toll-like and other PARs, which are important in multiple immune signaling pathways. Thus, the direct implication of PAR2 in…
Duodenal Bacteria From Patients With Celiac Disease and Healthy Subjects Distinctly Affect Gluten Breakdown and Immunogenicity
Background & Aims Partially degraded gluten peptides from cereals trigger celiac disease (CD), an autoimmune enteropathy occurring in genetically susceptible persons. Susceptibility genes are necessary but not sufficient to induce CD, and additional environmental factors related to unfavorable alterations in the microbiota have been proposed. We investigated gluten metabolism by opportunistic pathogens and commensal duodenal bacteria and characterized the capacity of the produced peptides to activate gluten-specific T-cells from CD patients. Methods We colonized germ-free C57BL/6 mice with bacteria isolated from the small intestine of CD patients or healthy controls, selected for their in v…
The Risk of Contracting COVID-19 Is Not Increased in Patients With Celiac Disease
The World Health Organization declared coronavirus disease-2019 (COVID-19) a global pandemic in March 2020. Since then, there are more than 34 million cases of COVID-19 leading to more than 1 million deaths worldwide. Numerous studies suggest that celiac disease (CeD), a chronic immune-mediated gastrointestinal condition triggered by gluten, is associated with an increased risk of respiratory infections.(1-3) However, how it relates to the risk of COVID-19 is unknown. To address this gap, we conducted a cross-sectional study to evaluate whether patients with self-reported CeD are at an increased risk of contracting COVID-19.
Lactobacilli Degrade Wheat Amylase Trypsin Inhibitors to Reduce Intestinal Dysfunction Induced by Immunogenic Wheat Proteins.
Background & Aims Wheat-related disorders, a spectrum of conditions induced by the ingestion of gluten-containing cereals, have been increasing in prevalence. Patients with celiac disease have gluten-specific immune responses, but the contribution of non-gluten proteins to symptoms in patients with celiac disease or other wheat-related disorders is controversial. Methods C57BL/6 (control), Myd88–/–, Ticam1–/–, and Il15–/– mice were placed on diets that lacked wheat or gluten, with or without wheat amylase trypsin inhibitors (ATIs), for 1 week. Small intestine tissues were collected and intestinal intraepithelial lymphocytes (IELs) were measured; we also investigated gut permeability and int…
Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment.
Celiac disease (CeD) is a frequent immune-mediated disease that affects not only the small intestine but also many extraintestinal sites. The role of gluten proteins as dietary triggers, HLA-DQ2 or -DQ8 as major necessary genetic predisposition, and tissue transglutaminase (TG2) as mechanistically involved autoantigen, are unique features of CeD. Recent research implicates many cofactors working in synergism with these key triggers, including the intestinal microbiota and their metabolites, nongluten dietary triggers, intestinal barrier defects, novel immune cell phenotypes, and mediators and cytokines. In addition, apart from HLA-DQ2 and -DQ8, multiple and complex predisposing genetic fact…
A266 AMYLASE TRYPSIN INHIBITORS FROM WHEAT EXACERBATE GLUTEN-INDUCED PATHOLOGY AND ALTER GUT MICROBIOTA IN MICE
BACKGROUND: Celiac disease (CeD) is an autoimmune enteropathy triggered by gluten in genetically susceptible individuals expressing HLA DQ2 or DQ8. The adaptive immune response is characterized by a gluten-specific T-cells, anti-gluten and anti-tissue transglutaminase-2 antibodies. Proliferation and activation of intraepithelial lymphocytes (IELs) is central to the innate immune response, although the triggers and receptors remain unclear. Amylase trypsin inhibitors (ATIs) are pest-resistant molecules in modern wheat with TLR4-activating capacities in mononuclear phagocytic cells. AIMS: Our aim was to determine whether ATIs act as innate activators, enhancing gluten immunopathology in mice.…
A49 LACTOBACILLI DEGRADE WHEAT AMYLASE TRYPSIN INHIBITORS (ATI) TO AMELIORATE GUT DYSFUNCTION INDUCED BY IMMUNOGENIC WHEAT PROTEINS
BACKGROUND: Wheat-related disorders involve a wide spectrum of conditions, triggered by the ingestion of gluten-containing cereals. The induction of gluten-specific immune responses in celiac disease is well established. However, the contribution of gluten and/or non-gluten proteins in the generation of symptoms in other wheat-related disorders is controversial. Amylase trypsin inhibitors (ATIs) are pest-resistant molecules in modern wheat with TLR4-activating capacities. AIMS: We investigated the role of ATIs in the generation of gut barrier dysfunction and dysmotility in wild-type mice as well as in the severity of gluten-induced immunopathology in genetically predisposed mice. We also de…
Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG
Background & Aims Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. Methods We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiot…
Risk perception and knowledge of COVID-19 in patients with celiac disease
BACKGROUND We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk. AIM To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception. METHODS We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visi…