Increased serum levels of lipopolysaccharide and antiflagellin antibodies in patients with diarrhea-predominant irritable bowel syndrome

被引:95
作者
Dlugosz, A. [1 ,2 ]
Nowak, P. [3 ]
D'Amato, M. [4 ]
Mohammadian Kermani, G. [1 ,2 ]
Nystrom, J. [5 ]
Abdurahman, S. [6 ]
Lindberg, G. [1 ,2 ]
机构
[1] Karolinska Univ Hosp, Karolinska Inst, Dept Med, SE-14186 Stockholm, Sweden
[2] Karolinska Univ Hosp, Karolinska Inst, Ctr Digest Dis, SE-14186 Stockholm, Sweden
[3] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Infect Dis Unit, SE-14186 Stockholm, Sweden
[4] Karolinska Univ Hosp, Karolinska Inst, Dept Biosci & Nutr, SE-14186 Stockholm, Sweden
[5] Karolinska Univ Hosp, Karolinska Inst, Div Clin Microbiol, Dept Lab Med, SE-14186 Stockholm, Sweden
[6] Univ Orebro, Orebro Life Sci Ctr, Dept Sci & Technol, SE-70182 Orebro, Sweden
关键词
Flagellin; irritable bowel syndrome; lipopolysaccharide; soluble CD14; toll-like receptors; BACTERIAL TRANSLOCATION; CROHNS-DISEASE; SOLUBLE CD14; BINDING PROTEIN; INCREASED IGA; FLAGELLIN; POLYMORPHISMS; ACTIVATION; MARKERS; GUT;
D O I
10.1111/nmo.12670
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BackgroundInnate 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. MethodsWe 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. Key ResultsWe 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 ( = 0.38; p = 0.0045). Conclusions & InferencesOur 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.
引用
收藏
页码:1747 / 1754
页数:8
相关论文
共 44 条
[1]   Inflammatory bowel disease and irritable bowel syndrome: similarities and differences [J].
Barbara, Giovanni ;
Cremon, Cesare ;
Stanghellini, Vincenzo .
CURRENT OPINION IN GASTROENTEROLOGY, 2014, 30 (04) :352-358
[2]   Role of Toll Like Receptors in Irritable Bowel Syndrome: Differential Mucosal Immune Activation According to the Disease Subtype [J].
Belmonte, Liliana ;
Youmba, Stephanie Beutheu ;
Bertiaux-Vandaele, Nathalie ;
Antonietti, Michel ;
Lecleire, Stephane ;
Zalar, Alberto ;
Gourcerol, Guillaume ;
Leroi, Anne-Marie ;
Dechelotte, Pierre ;
Coeffier, Moise ;
Ducrotte, Philippe .
PLOS ONE, 2012, 7 (08)
[3]   Has toll-like receptor 4 been prematurely dismissed as an inflammatory bowel disease gene? Association study combined with meta-analysis shows strong evidence for association [J].
Browning, Brian L. ;
Huebner, Claudia ;
Petermann, Ivonne ;
Gearry, Richard B. ;
Barclay, Murray L. ;
Shelling, Andrew N. ;
Ferguson, Lynnette R. .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (11) :2504-2512
[4]   Intestinal barrier function in health and gastrointestinal disease [J].
Camilleri, M. ;
Madsen, K. ;
Spiller, R. ;
Van Meerveld, B. G. ;
Verne, G. N. .
NEUROGASTROENTEROLOGY AND MOTILITY, 2012, 24 (06) :503-512
[5]   Enteric bacteria, lipopolysaccharides and related cytokines in inflammatory bowel disease: biological and clinical significance [J].
Caradonna, L ;
Amati, L ;
Magrone, T ;
Pellegrino, NM ;
Jirillo, E ;
Caccavo, D .
JOURNAL OF ENDOTOXIN RESEARCH, 2000, 6 (03) :205-214
[6]   Soluble-CD14: Role in atopic disease and recurrent infections, including otitis media [J].
Carlsen, Karin C. Lodrup ;
Granum, Berit .
CURRENT ALLERGY AND ASTHMA REPORTS, 2007, 7 (06) :436-443
[7]  
Dlugosz A, 2013, GUT MICR HLTH 2 WORL
[8]   No difference in small bowel microbiota between patients with irritable bowel syndrome and healthy controls [J].
Dlugosz, Aldona ;
Winckler, Bjorn ;
Lundin, Elin ;
Zakikhany, Katherina ;
Sandstrom, Gunnar ;
Ye, Weimin ;
Engstrand, Lars ;
Lindberg, Greger .
SCIENTIFIC REPORTS, 2015, 5
[9]   Circulating CD4+ and CD8+ T cells are activated in inflammatory bowel disease and are associated with plasma markers of inflammation [J].
Funderburg, Nicholas T. ;
Park, Samantha R. Stubblefield ;
Sung, Hannah C. ;
Hardy, Gareth ;
Clagett, Brian ;
Ignatz-Hoover, James ;
Harding, Clifford V. ;
Fu, Pingfu ;
Katz, Jeffry A. ;
Lederman, Michael M. ;
Levine, Alan D. .
IMMUNOLOGY, 2013, 140 (01) :87-97
[10]   Leaky Gut in Patients with Diarrhea-Predominant Irritable Bowel Syndrome and Inactive Ulcerative Colitis [J].
Gecse, Krisztina ;
Roka, Richard ;
Sera, Terez ;
Rosztoczy, Andras ;
Annahazi, Anita ;
Izbeki, Ferenc ;
Nagy, Ferenc ;
Molnar, Tamas ;
Szepes, Zoltan ;
Pavics, Laszlo ;
Bueno, Lionel ;
Wittmann, Tibor .
DIGESTION, 2012, 85 (01) :40-46