Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study

Michele Linsalata, Giuseppe Riezzo, Benedetta D'Attoma, Caterina Clemente, Antonella Orlando, Francesco Russo

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Alterations of the small-intestinal permeability (s-IP) might play an essential role in both diarrhoea-predominant IBS (D-IBS) and celiac disease (CD) patients. Our aims were to analyse in D-IBS patients the symptom profile along with the levels of urinary sucrose (Su), lactulose (La), mannitol (Ma), and circulating biomarkers (zonulin, intestinal fatty acid binding protein - I-FABP, and diamine oxidase - DAO) of the gastrointestinal (GI) barrier function. The pro-inflammatory interleukins 6 and 8 (IL-6 and IL-8), the plasma values of lipopolysaccharide (LPS), and Toll-like receptor 4 (TLR-4) were also investigated. Besides, these biomarkers were compared with those in CD and healthy controls (HC). Finally, comparisons were performed between D-IBS patients with [D-IBS(+)] and without [D-IBS(-)] increased s-IP according to normal or altered La/Ma ratio.

METHODS: The study included 39 D-IBS patients, 32 CD patients, and 20 HC. GI permeability was assayed by high-performance liquid chromatography determination in the urine of Su and La/Ma ratio. ELISA kits assayed circulating concentrations of zonulin, I-FABP, DAO, IL-6, IL-8, LPS, and TLR-4. The Mann-Whitney or the Kruskal-Wallis with Dunn's post-test was used to assess differences among the groups.

RESULTS: As for the La/Ma ratio, %Su, and I-FABP levels, D-IBS patients were significantly different from CD, but not HC. IL-6 levels were significantly higher in CD than HC, whereas IL-8 levels were significantly higher in both D-IBS and CD patients than HC. By opposite, LPS, and TLR-4 concentrations did not differ significantly among the groups. When D-IBS patients were categorised according to normal or altered s-IP, D-IBS(+) patients had %La, %Su, I-FABP, and DAO levels significantly higher than D-IBS(-) ones. The inflammatory parameters and markers of bacterial translocation (namely, IL-6 and LPS) were significantly higher in D-IBS(+) patients than D-IBS(-) ones.

CONCLUSIONS: The present study suggests that two distinct D-IBS subtypes could be identified. The investigation of possible s-IP alterations (i.e., considering the La/Ma ratio) might be useful to assess better and categorise this heterogeneous D-IBS population.

TRIAL REGISTRATION: NCT01574209 . Registered March 2012. First recruitment started in April 2012.

Original languageEnglish
Pages (from-to)167
Number of pages14
JournalBMC Gastroenterology
Issue number1
Publication statusPublished - Nov 6 2018


  • Adult
  • Amine Oxidase (Copper-Containing)/blood
  • Biomarkers/blood
  • Case-Control Studies
  • Celiac Disease/blood
  • Cholera Toxin/blood
  • Diarrhea/diagnosis
  • Fatty Acid-Binding Proteins/blood
  • Female
  • Humans
  • Interleukins/blood
  • Intestinal Mucosa/metabolism
  • Irritable Bowel Syndrome/classification
  • Lactulose/urine
  • Lipopolysaccharides/blood
  • Male
  • Mannitol/urine
  • Middle Aged
  • Permeability
  • Sucrose/urine
  • Surveys and Questionnaires
  • Toll-Like Receptor 4/blood


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