title: Presence of commensal house dust mite allergen in human gastrointestinal tract: a potential contributor to intestinal barrier dysfunction.
abstract: BACKGROUND
  Abnormal gut barrier function is the basis of gut inflammatory disease. It is known that house dust mite (HDM) aero-allergens induce inflammation in respiratory mucosa. We have recently reported allergen from Dermatophagoides pteronyssinus (Der p1) to be present in rodent gut.
  
  
  OBJECTIVE
  To examine whether Der p1 is present in human gut and to assess its effect on gut barrier function and inflammation.
  
  
  METHODS
  Colonic biopsies, gut fluid, serum and stool were collected from healthy adults during endoscopy. Der p1 was measured by ELISA. Effect of HDM was assessed on gut permeability, tight-junction and mucin expression, and cytokine production, in presence or absence of cysteine protease inhibitors or serine protease inhibitors. In vivo effect of HDM was examined in mice given oral HDM or protease-neutralised HDM. Role of HDM in low-grade inflammation was studied in patients with IBS.
  
  
  RESULTS
  HDM Der p1 was detected in the human gut. In colonic biopsies from healthy patients, HDM increased epithelial permeability (p<0.001), reduced expression of tight-junction proteins and mucus barrier. These effects were associated with increased tumour necrosis factor (TNF)-α and interleukin (IL)-10 production and were abolished by cysteine-protease inhibitor (p<0.01). HDM effects did not require Th2 immunity. Results were confirmed in vivo in mice. In patients with IBS, HDM further deteriorated gut barrier function, induced TNF-α but failed to induce IL-10 secretion (p<0.001).
  
  
  CONCLUSIONS
  HDM, a ubiquitous environmental factor, is present in the human gut where it directly affects gut function through its proteolytic activity. HDM may be an important trigger of gut dysfunction and warrants further investigation.
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France The International Inflammation 'in-FLAME' Network, Worldwide Universities Network.
authors.forename: Meri K
authors.initials: MK
authors.lastname: Tulic
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Immunology, Hôpital Archet 1, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: Mylene
authors.initials: M
authors.lastname: Vivinus-Nébot
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France.
authors.forename: Akila
authors.initials: A
authors.lastname: Rekima
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Samara
authors.initials: S
authors.lastname: Rabelo Medeiros
authors.affiliation: INSERM U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France CNRS, U5282, Toulouse, France Université de Toulouse, Site Paul Sabatier (UPS), Toulouse, France.
authors.forename: Chrystelle
authors.initials: C
authors.lastname: Bonnart
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Haining
authors.initials: H
authors.lastname: Shi
authors.affiliation: Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Walker
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Dainese
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Boyer
authors.affiliation: INSERM U1043, Centre de Physiopathologie de Toulouse Purpan (CPTP), Toulouse, France CNRS, U5282, Toulouse, France Université de Toulouse, Site Paul Sabatier (UPS), Toulouse, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Vergnolle
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France Department of Gastroenterology and Nutrition, Hôpital Archet 2, CHU de Nice, Université de Nice Sophia-Antipolis, Nice, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Piche
authors.affiliation: Université de Nice Sophia-Antipolis, EA 6302 Immune Tolerance (TIM), Nice, France The International Inflammation 'in-FLAME' Network, Worldwide Universities Network.
authors.forename: Valérie
authors.initials: V
authors.lastname: Verhasselt
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000302:isolation & purification*; D040002:Dermatophagoides pteronyssinus / Q000276:immunology*; D005767:Gastrointestinal Diseases / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D039741:Antigens, Dermatophagoides
keywords: EPITHELIAL PERMEABILITY; GASTROINTESTINAL IMMUNE RESPONSE; GASTROINTESTINAL TRACT; GUT IMMUNOLOGY; GUT INFLAMMATION