Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment

Verdú, Elena F.; Schuppan, Detlef

doi:10.1053/j.gastro.2021.08.016

Cited by 43 publications

(25 citation statements)

References 218 publications

(201 reference statements)

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“…Most recent published studies focus on childhood infections, which could lead to alteration of the intestinal microbiota following the administration of antibiotics [ 163 , 164 , 165 , 166 ].…”

Section: Discussionmentioning

confidence: 99%

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Ailioaie

Litscher

et al. 2022

IJMS

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Celiac disease (CD) comprises over 1% of the world’s population and is a chronic multisystem immune-mediated condition manifested by digestive and/or extradigestive symptoms caused by food intake of gluten. This review looked at the risk of children diagnosed with CD developing SARS-CoV-2 infection and possible severe forms of COVID-19. A better understanding of the interaction and effects of SARS-CoV-2 infection in CD is very important, as is the role of environmental and genetic factors, but especially the molecular mechanisms involved in modulating intestinal permeability with impact on autoimmunity. CD inspired the testing of a zonulin antagonist for the fulminant form of multisystem inflammatory syndrome in children (MIS-C) and paved the way for the discovery of new molecules to regulate the small intestine barrier function and immune responses. Original published works on COVID-19 and CD, new data and points of view have been analyzed because this dangerous virus SARS-CoV-2 is still here and yet influencing our lives. Medical science continues to focus on all uncertainties triggered by SARS-CoV-2 infection and its consequences, including in CD. Although the COVID-19 pandemic seems to be gradually extinguishing, there is a wealth of information and knowledge gained over the last two years and important life lessons to analyze, as well as relevant conclusions to be drawn to deal with future pandemics. Zonulin is being studied extensively in immunoengineering as an adjuvant to improving the absorption of new drugs and oral vaccines.

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Section: Discussionmentioning

confidence: 99%

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Ailioaie

Litscher

et al. 2022

IJMS

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“…In turn, prebiotic consumption drives the abundance of SCFA-producing microbes in the gut (Golfetto et al, 2014;Makki et al, 2018). However, as recently reviewed by Verdu and Schuppan (2021), due to controversial results, the microbiota composition in CD did not show a unique fingerprint. Although some taxa shared common tendencies (i.e., increased abundance of Proteobacteria, Neisseria, and Escherichia coli as well as a decreased abundance of Bifidobacterium and Bacteroides ovatus), not a unique microbiota fingerprint is consistent with CD.…”

Section: Discussionmentioning

confidence: 94%

How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review

et al. 2022

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Celiac disease (CD) is an inflammatory autoimmune disorder triggered by the ingestion of gluten from wheat and other cereals. Nowadays, its positive diagnosis is based on invasive approaches such as the histological examination of intestinal biopsies and positive serology screening of antibodies. After proven diagnosis, the only admissible treatment for CD individuals is strict life-long adherence to gluten-free diet (GFD), although it is not a conclusive therapy. Acting by different mechanisms and with different etiologies, both CD and GFD have a great impact on gut microbiota that result in a different taxa composition. Altered production of specific metabolites reflects these microbiota changes. In this light, the currently available literature reports some suggestions about the possible use of specific metabolites, detected by meta-omics analyses, as potential biomarkers for a CD non-invasive diagnosis. To highlight insights about metabolomics application in CD study, we conducted a narrative dissertation of selected original articles published in the last decade. By applying a systematic search, it clearly emerged how the metabolomic signature appears to be contradictory, as well as poorly investigated.

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“…The concordance of about 75% between monozygotic twins vs 12% in monozygotic twins stresses the importance of genetic factors 78. HLA-DQ2/8, the major risk factor is generally considered to account for 35% of the genetic predisposition 79. A recent very large genome-wide association study (GWAS) suggests however a lesser contribution of 23% when calculations are based on a CD prevalence of 1% 80.…”

Section: Additional Factors and Environmental Triggers In Coeliac Dis...mentioning

confidence: 99%

“…It seems indeed possible that recent changes in the microbiota might have contributed to the twofold to threefold increase in CD prevalence observed over the past 50 years 2 107. Numerous observational studies have documented differences in the microbiota of patients with CD compared with controls, yet with little consistency except for an increase in proteobacteria and a decrease in species associated with anti-inflammatory properties, a finding reported in many chronic inflammatory intestinal conditions 79. Interestingly however, several studies have provided mechanistic insight into the potential beneficial versus deleterious effects of the microbiota in CD 108.…”

Section: Additional Factors and Environmental Triggers In Coeliac Dis...mentioning

confidence: 99%

Immunopathogenesis and environmental triggers in coeliac disease

Levescot

Malamut

Cerf‐Bensussan

2022

Gut

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Coeliac disease (CD) is a frequent immune enteropathy induced by gluten in genetically predisposed individuals. Its pathogenesis has been extensively studied and CD has emerged as a model disease to decipher how the interplay between environmental and genetic factors can predispose to autoimmunity and promote lymphomagenesis. The keystone event is the activation of a gluten-specific immune response that is driven by molecular interactions between gluten, the indispensable environmental factor, HLA-DQ2/8, the main predisposing genetic factor and transglutaminase 2, the CD-specific autoantigen. The antigluten response is however not sufficient to induce epithelial damage which requires the activation of cytotoxic CD8+ intraepithelial lymphocytes (IEL). In a plausible scenario, cooperation between cytokines released by gluten-specific CD4+ T cells and interleukin-15 produced in excess in the coeliac gut, licenses the autoimmune-like attack of the gut epithelium, likely via sustained activation of the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway in IEL. Demonstration that lymphomas complicating CD arise from IEL that have acquired gain-of-function JAK1 or STAT3 mutations stresses the key role of this pathway and explains how gluten-driven chronic inflammation may promote this rare but most severe complication. If our understanding of CD pathogenesis has considerably progressed, several questions and challenges remain. One unsolved question concerns the considerable variability in disease penetrance, severity and presentation, pointing to the role of additional genetic and environmental factors that remain however uneasy to untangle and hierarchize. A current challenge is to transfer the considerable mechanistic insight gained into CD pathogenesis into benefits for the patients, notably to alleviate the gluten-free diet, a burden for many patients.

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Co-factors, Microbes, and Immunogenetics in Celiac Disease to Guide Novel Approaches for Diagnosis and Treatment

Cited by 43 publications

References 218 publications

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

Celiac Disease and Targeting the Molecular Mechanisms of Autoimmunity in COVID Pandemic

How Metabolomics Provides Novel Insights on Celiac Disease and Gluten-Free Diet: A Narrative Review

Immunopathogenesis and environmental triggers in coeliac disease

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