title: Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome.
abstract: BACKGROUND
  Innate immune responses to conserved microbial products such as lipopolysaccharide (LPS) and flagellin are likely important in microbial-host interactions and intestinal homeostasis. We hypothesized that bacterial translocation and activation of mucosal immunity against common microbial antigens might be involved in the development of irritable bowel syndrome (IBS). We therefore compared serum levels of LPS, soluble CD14 (sCD14), and flagellin antibodies between patients with different subtypes of IBS and healthy controls.
  
  
  METHODS
  We analyzed serum obtained from 88 patients (74 females) aged 19(43)-73 years and 106 healthy volunteers (77 females) aged 19(38)-62 years. Diarrhea-predominant IBS (D-IBS) was present in 32 patients (36%), 23 patients (26%) had constipation-predominant IBS (C-IBS), and 33 patients (38%) had A-IBS. We used ELISA for sCD14 and antiflagellin immunoglobulin G and limulus amebocyte assay for LPS. Abdominal symptoms and psychiatric comorbidities were assessed using validated questionnaires.
  
  
  RESULTS
  We found a significantly higher serum level of LPS in patients with D-IBS compared to controls (p = 0.0155). The level of antibodies to flagellin was higher in patients with IBS than in controls (mainly driven by higher levels in D-IBS, p = 0.0018). The levels of sCD14 were lower in D-IBS patients compared to controls (p = 0.0498). We found a weak, but significant correlation between the levels of antiflagellin antibodies and anxiety among IBS patients (ρ = 0.38; p = 0.0045).
  
  
  CONCLUSIONS
  Our results support the concept that immune reactivity to luminal antigens may have a role in the development of D-IBS. The serum level of antiflagellin antibodies was found to correlate with patients' self-reported anxiety score.
authors.affiliation: Karolinska Institutet, Department of Medicine and Center for Digestive Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Dlugosz
authors.affiliation: Karolinska Institutet, Department of Medicine, Unit of Infectious Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Nowak
authors.affiliation: Karolinska Institutet, Department of Biosciences and Nutrition, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: D'Amato
authors.affiliation: Karolinska Institutet, Department of Medicine and Center for Digestive Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Mohammadian Kermani
authors.affiliation: Karolinska Institutet, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Nyström
authors.affiliation: Department of Science and Technology, Örebro Life Science Center, Örebro University, Örebro, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Abdurahman
authors.affiliation: Karolinska Institutet, Department of Medicine and Center for Digestive Diseases, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Lindberg
mesh_terms: D000328:Adult; D000368:Aged; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D003967:Diarrhea / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005408:Flagellin / Q000276:immunology*; D005838:Genotype; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000235:genetics / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D051193:Toll-Like Receptors / Q000235:genetics; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D005408:Flagellin
keywords: Flagellin; irritable bowel syndrome; lipopolysaccharide; soluble CD14; toll-like receptors