title: Reduced Mucosa-associated Butyricicoccus Activity in Patients with Ulcerative Colitis Correlates with Aberrant Claudin-1 Expression.
abstract: OBJECTIVE
  Butyricicoccus is a butyrate-producing clostridial cluster IV genus whose numbers are reduced in the stool of ulcerative colitis [UC] patients. Conditioned medium of Butyricicoccus [B.] pullicaecorum prevents tumour necrosis factor alpha [TNFα]-induced increase in epithelial permeability in vitro. Since butyrate influences intestinal barrier integrity, we further investigated the relationship between the abundance of mucosa-associated Butyricicoccus and the expression of butyrate-regulated tight junction [TJ] genes.
  
  
  METHODS
  Tight junction protein 1 [TJP1], occludin [OCLN], claudin-1 [CLDN1], and Butyricicoccus 16S rRNA expression was analysed in a collection of colonic biopsies of healthy controls and UC patients with active disease. The effect of butyrate and B. pullicaecorum conditioned medium on TJ gene expression was investigated in TNFα-stimulated Caco-2 monolayers and inflamed mucosal biopsies of UC patients.
  
  
  RESULTS
  TJP1 expression was significantly decreased in inflamed UC mucosa, whereas CLDN1 mRNA levels were increased. OCLN did not differ significantly between the groups. Mucosa-associated Butyricicoccus 16S rRNA transcripts were reduced in active UC patients compared with healthy controls. Interestingly, Butyricicoccus activity negatively correlated with CLDN1 expression. Butyrate reversed the inflammation-induced increase of CLDN1 protein levels, and stimulation of inflamed UC biopsies with B. pullicaecorum conditioned medium normalized CLDN1 mRNA levels.
  
  
  CONCLUSIONS
  Butyricicoccus is a mucosa-associated bacterial genus under-represented in colonic mucosa of patients with active UC, whose activity inversely correlates with CLDN1 expression. Butyrate and B. pullicaecorum conditioned medium reduce CLDN1 expression, supporting its use as a pharmabiotic preserving epithelial TJ integrity.
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Devriese
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Ghent University, Merelbeke, Belgium.
authors.forename: Venessa
authors.initials: V
authors.lastname: Eeckhaut
authors.affiliation: Laboratory of Microbial Ecology and Technology [LabMET], Ghent University, Ghent, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Geirnaert
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Lien
authors.initials: L
authors.lastname: Van den Bossche
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Hindryckx
authors.affiliation: Laboratory of Microbial Ecology and Technology [LabMET], Ghent University, Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van de Wiele
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Ghent University, Merelbeke, Belgium.
authors.forename: Filip
authors.initials: F
authors.lastname: Van Immerseel
authors.affiliation: Department of Pathology, Bacteriology and Avian Diseases, Ghent University, Merelbeke, Belgium.
authors.forename: Richard
authors.initials: R
authors.lastname: Ducatelle
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: De Vos
authors.affiliation: Department of Gastroenterology, Ghent University, Ghent, Belgium debby.laukens@ugent.be.
authors.forename: Debby
authors.initials: D
authors.lastname: Laukens
mesh_terms: D000328:Adult; D001706:Biopsy / Q000379:methods; D002087:Butyrates / Q000378:metabolism; D018938:Caco-2 Cells; D062445:Claudin-1 / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D005051:Eubacterium / Q000302:isolation & purification / Q000502:physiology; D005243:Feces / Q000382:microbiology; D005260:Female; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D008297:Male; D062793:Occludin / Q000378:metabolism*; D062072:Patient Acuity; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D013223:Statistics as Topic; D019108:Tight Junctions / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D002087:Butyrates; D062445:Claudin-1; D062793:Occludin; D012336:RNA, Ribosomal, 16S; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein
keywords: Tight junctions; butyrate; pharmabiotic