title: The Interaction among Microbiota, Immunity, and Genetic and Dietary Factors Is the Condicio Sine Qua Non Celiac Disease Can Develop.
abstract: Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.
authors.affiliation: Institute of Internal Medicine, Catholic University, 00168 Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pagliari
authors.affiliation: Gastroenterology and Digestive Endoscopy Unit, Belcolle Hospital, 01100 Viterbo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Urgesi
authors.affiliation: Institute of Internal Medicine, Catholic University, 00168 Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Frosali
authors.affiliation: Digestive Endoscopy Unit, Catholic University, 00168 Rome, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Riccioni
authors.affiliation: CytoCure LLC, Beverly, MA 01915, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Newton
authors.affiliation: Institute of Internal Medicine, Catholic University, 00168 Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Landolfi
authors.affiliation: Institute of Internal Medicine, Catholic University, 00168 Rome, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Pandolfi
authors.affiliation: Institute of Internal Medicine, Catholic University, 00168 Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Cianci
mesh_terms: D000818:Animals; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D004032:Diet / Q000379:methods; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007107:Immune System / Q000276:immunology*; D064307:Microbiota / Q000276:immunology*