title: Differences in gluten metabolism among healthy volunteers, coeliac disease patients and first-degree relatives.
abstract: Coeliac disease (CD) is an immune-mediated enteropathy resulting from exposure to gluten in genetically predisposed individuals. Gluten proteins are partially digested by human proteases generating immunogenic peptides that cause inflammation in patients carrying HLA-DQ2 and DQ8 genes. Although intestinal dysbiosis has been associated with patients with CD, bacterial metabolism of gluten has not been studied in depth thus far. The aim of this study was to analyse the metabolic activity of intestinal bacteria associated with gluten intake in healthy individuals, CD patients and first-degree relatives of CD patients. Faecal samples belonging to twenty-two untreated CD patients, twenty treated CD patients, sixteen healthy volunteers on normal diet, eleven healthy volunteers on gluten-free diet (GFD), seventy-one relatives of CD patients on normal diet and sixty-nine relatives on GFD were tested for several proteolytic activities, cultivable bacteria involved in gluten metabolism, SCFA and the amount of gluten in faeces. We detected faecal peptidasic activity against the gluten-derived peptide 33-mer. CD patients showed differences in faecal glutenasic activity (FGA), faecal tryptic activity (FTA), SCFA and faecal gluten content with respect to healthy volunteers. Alterations in specific bacterial groups metabolising gluten such as Clostridium or Lactobacillus were reported in CD patients. Relatives showed similar parameters to CD patients (SCFA) and healthy volunteers (FTA and FGA). Our data support the fact that commensal microbial activity is an important factor in the metabolism of gluten proteins and that this activity is altered in CD patients.
authors.affiliation: 1Instituto de Biología Molecular,Genómica y Proteómica (INBIOMIC),Campus de Vegazana,Universidad de León,León 24071,Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Caminero
authors.affiliation: 2Área de Microbiología, Facultad de Biología y Ciencias Ambientales,Universidad de León,León 24071,Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Nistal
authors.affiliation: 1Instituto de Biología Molecular,Genómica y Proteómica (INBIOMIC),Campus de Vegazana,Universidad de León,León 24071,Spain.
authors.forename: Alexandra R
authors.initials: AR
authors.lastname: Herrán
authors.affiliation: 2Área de Microbiología, Facultad de Biología y Ciencias Ambientales,Universidad de León,León 24071,Spain.
authors.forename: Jénifer
authors.initials: J
authors.lastname: Pérez-Andrés
authors.affiliation: 3Área de Bioquímica, Facultad de Biología y Ciencias Ambientales,Universidad de León,León 24071,Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ferrero
authors.affiliation: 4Departamento de Gastroenterología,Hospital de León,Altos de Nava s/n,León 24071,Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Vaquero Ayala
authors.affiliation: 4Departamento de Gastroenterología,Hospital de León,Altos de Nava s/n,León 24071,Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Vivas
authors.affiliation: 5Instituto de Biomedicina (IBIOMED) Campus de Vegazana,Universidad de León,León 24071,Spain.
authors.forename: José M G
authors.initials: JM
authors.lastname: Ruiz de Morales
authors.affiliation: 7Instituto de Biotecnología (INBIOTEC) de León,Avenida Real,León 1 24006,Spain.
authors.forename: Silvia M
authors.initials: SM
authors.lastname: Albillos
authors.affiliation: 1Instituto de Biología Molecular,Genómica y Proteómica (INBIOMIC),Campus de Vegazana,Universidad de León,León 24071,Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Casqueiro
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D039903:Actinobacteria / Q000302:isolation & purification / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000483:Alleles; D020148:Butyric Acid / Q000378:metabolism; D002208:Caproates / Q000378:metabolism; D002446:Celiac Disease / Q000178:diet therapy*; D055050:Diet, Gluten-Free; D005243:Feces / Q000737:chemistry; D000068536:Bacillota / Q000302:isolation & purification / Q000378:metabolism; D005983:Glutens / Q000008:administration & dosage* / Q000378:metabolism*; D006683:HLA-DQ Antigens / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology; D008875:Middle Aged; D010421:Pentanoic Acids / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D020560:Proteobacteria / Q000302:isolation & purification / Q000378:metabolism; D055815:Young Adult
chemical_list: D002208:Caproates; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D010421:Pentanoic Acids; D011422:Propionates; D020148:Butyric Acid; C037652:hexanoic acid; D005983:Glutens; C038780:n-pentanoic acid; C029658:propionic acid; D019342:Acetic Acid
keywords: CD coeliac disease; Coeliac disease; DGGE denaturing gradient gel electrophoresis; FDPPIV faecal dipeptidyl peptidasic IV activity; FGA faecal glutenasic activity; FPEP faecal prolyl endopeptidasic activity; FTA faecal tryptic activity; GFD gluten-free diet; Gluten metabolism; Intestinal proteases; Microbial activity