Circulating Anti-cytolethal Distending Toxin B and Anti-vinculin Antibodies as Biomarkers in Community and Healthcare Populations With Functional Dyspepsia and Irritable Bowel Syndrome

Abstract

OBJECTIVES: Anti-cytolethal distending toxin B (CdtB) and anti-vinculin antibodies have been proposed as biomarkers that discriminate irritable bowel syndrome (IBS) diarrhea from inflammatory bowel disease; however, it is unknown whether they can also discriminate patients with IBS and IBS subtypes and functional dyspepsia (FD) from healthy individuals in the general population. We aimed to determine whether anti-CdtB and anti-vinculin can discriminate IBS and FD from health and from organic gastrointestinal (GI) disease. METHODS: Adults were enrolled from 2 Australian studies: (i) a random, population-based study (n = 331) with subjects diagnosed with IBS (n = 63) or FD (n = 61) by modified Rome III criteria or healthy control subjects (n = 246) who did not meet criteria for IBS and/or FD and (ii) an outpatient-based study with subjects diagnosed with IBS (n = 256) and/or FD (n = 55) or organic GI disease (n = 182) by an independent clinician. Serum levels of anti-CdtB/anti-vinculin antibodies were determined by enzyme-linked immunosorbent assay. RESULTS: There was a significantly higher mean value of anti-CdtB in FD vs healthy controls (mean = 2.46 [SD = 0.72] vs mean = 2.14 [SD = 0.77]; P = 0.005) and IBS/FD overlap vs healthy controls (mean = 2.47 [SD = 0.78] vs mean = 2.14 [SD = 0.77]; P = 0.02). There were no significant differences in anti-CdtB in IBS and FD outpatients or IBS/FD subgroups compared with patients with organic GI disease. In terms of anti-vinculin, there were no significant differences between IBS and FD and healthy controls or between IBS and FD and organic GI disease controls. DISCUSSION: We did not confirm that anti-CdtB/anti-vinculin discriminated IBS diarrhea from organic GI disease in Australian subjects. However, we did find higher anti-CdtB in FD and IBS/FD overlap vs healthy controls. Postinfectious FD may be more common than currently recognized.

Novel concepts in the pathophysiology and treatment of functional dyspepsia

“…Immune activation in the pathogenesis of FD is very evident in the postinfectious setting,77 with persisting changes in duodenal mucosal immune cells after the initial event and systemic immune activation in acute compared with unspecified-onset FD, indicating the inability of the immune system to recover from the triggering infectious insult 77 78. Similar to studies in IBS, antibodies to cytolethal distending toxin B, produced by Gram-negative bacteria causing acute gastroenteritis, were more common in FD and IBS/FD overlap compared with healthy controls in an Australian population-based study, suggesting possible under-recognition of postinfectious FD 79. The disruption in structural and/or functional microbial configuration, defined as ‘dysbiosis’, has been studied in both functional and inflammatory GI disorders 80 81.…”

Small Intestinal Bacterial Overgrowth and Irritable Bowel Syndrome – An Update

“…Vinculin is a key cytoskeletal protein that plays an essential role in cell-matrix and cell-cell adhesion ( 69 ). In humans, numerous studies have found that these two biomarkers (antibodies to CdtB and vinculin) can differentiate between IBS-D/M ( 70 – 73 ) and other bowel diseases and conditions that cause diarrhea, although one study in Australia failed to show such relationship ( 74 ). A longitudinal observation of a single patient who developed IBS after an episode of infectious diarrhea demonstrated a subsequent elevation in anti-CdtB, followed by an elevation in anti-vinculin, each coinciding with symptoms ( 44 ).…”

Zonulin in serum as a biomarker fails to identify the IBS, functional dyspepsia and non-coeliac wheat sensitivity

“…Adult participants were recruited from two sources9; (1) a population-based study (n=242; mean age 62.1 (SD=11.9) years; 45.9% female) and (2) a two-site hospital-based study (n=102; mean age 45.0 (SD=16.2) years; 67.4% female). In the population-based study, IBS (n=40) and FD (n=42) were diagnosed according to modified Rome III criteria, while CD (n=6), gluten intolerance (n=6) and NCGS (n=44) had self-reported doctor diagnoses.…”