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Cited by 148Gastrointestinal motility and disordersGut microbiota and healthInflammatory Bowel Disease

Development and Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome in Human Subjects

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Pimentel, Mark, Morales, Walter, Rezaie, Ali, Marsh, Emily, Lembo, Anthony, Mirocha, James, Leffler, Daniel A., Marsh, Zachary +7 more·2015·PLOS ONE
DOI 10.1371/journal.pone.0126438PMC PMC4430499
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Abstract

Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density≥2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD≥1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.

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  • A validation study of antibodies to bacterial toxins and host cell adhesion proteins performed only modestly in distinguishing IBS from health.

    “A validation study of antibodies to bacterial toxins and host cell adhesion proteins performed only modestly in distinguishing IBS from health”

    From Irritable bowel syndrome (2020) · cites this paper as [134]

    The Results (Comparison of antibody titers between groups) show that anti-CdtB and anti-vinculin levels were higher in diarrhea-predominant IBS than in healthy controls. The Results (Sensitivity and specificity analyses) also say the IBS-versus-healthy-control ROC curves were discriminatory, but the reported AUCs and cutoff performance are for IBS versus inflammatory bowel disease. Those figures do not establish that discrimination from health was ‘only modest.’ (LLM, conf=0.76)

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Authors
Pimentel, M., Morales, W., Rezaie, A., Marsh, E., Lembo, A., Mirocha, J., Leffler, D. A., Marsh, Z., Weitsman, S., Chua, K. S., Barlow, G. M., Bortey, E., Forbes, W., Yu, A., & Chang, C.
Affiliations
  • Cedars-Sinai Medical Center (US)
  • Beth Israel Deaconess Medical Center (US)
  • Salix Pharmaceuticals (United States) (US)
Corresponding author
Pimentel, Mark
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2015-05-13
Volume
10
Issue
5
Pages
e0126438
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0126438
PMC
PMC4430499
OpenAlex
W2159708650
Cited by
148
References
3
Citations by year
2026: 10 · 2025: 11 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 17 · 2020: 16 · 2019: 12 · 2018: 11 · 2017: 16 · 2016: 24 · 2015: 10 · 2014: 1
FWCI
21.18
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Beatrice and Samuel A. Seaver Foundation
  • Cedars-Sinai Medical Center
  • National Institute of Diabetes and Digestive and Kidney Diseases (R03DK095937)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
diarrhea-predominant irritable bowel syndrome, biomarkers, post-infectious IBS, acute gastroenteritis, inflammatory bowel disease, celiac disease, diagnostic specificity, cross-reactive antibodies, Rome criteria, serological diagnosis, vinculin, Shigella
MeSH terms
Adolescent, Adult, Aged, Autoantibodies, Diagnosis, Differential, Diarrhea, Female, Humans, Male, Middle Aged, ROC Curve, Biomarkers, Case-Control Studies, Irritable Bowel Syndrome, Young Adult

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