Serum zonulin is elevated in IBS and correlates with stool frequency in IBS‐D

Singh, Prashant; Silvester, Jocelyn A.; Chen, Xinhua; Xu, Hua; Sawhney, Veer; Rangan, V. Kasturi; Iturrino, Johanna; Nee, Judy; Duerksen, Donald R.; Lembo, Anthony

doi:10.1177/2050640619826419

Cited by 40 publications

(28 citation statements)

References 35 publications

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“…Interestingly, serum zonulin levels were not significantly different between patients with IBD and those with IBS, suggesting impaired intestinal permeability in patients with functional intestinal diseases. Accordingly, it has been shown that serum zonulin is upregulated in IBS [23], particularly in patients with diarrhea-predominant type [24]. Taken together, these observations are consistent with the hypothesis that increased intestinal permeability may be a necessary but not sufficient condition for the development of several intestinal diseases.…”

Section: Discussionsupporting

confidence: 82%

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Caviglia

Rosso

Stalla

et al. 2020

JCM

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In patients with inflammatory bowel diseases (IBD) undergoing biologic therapy, biomarkers of treatment response are still scarce. This study aimed to evaluate whether serum zonulin, a biomarker of intestinal permeability; soluble CD163 (sCD163), a macrophage activation marker; and a panel of serum cytokines could predict the response to biologic treatment in patients with IBD. For this purpose, we prospectively enrolled 101 patients with IBD and 19 patients with irritable bowel syndrome (IBS) as a control group; 60 out of 101 patients underwent treatment with biologics. Zonulin, sCD163, and cytokines were measured at the baseline in all patients and after 10 weeks of treatment in the 60 patients who underwent biologic therapy. We observed that zonulin levels were higher in IBD patients with active disease compared to those in remission (p = 0.035), and that sCD163 values were higher in patients with IBD compared to those with IBS (p = 0.042), but no association with therapy response was observed for either biomarker. Conversely, interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha showed a significant reduction from baseline to week 10 of treatment, particularly in responder patients. By multivariate logistic regression analysis corrected for disease (Crohn’s disease or ulcerative colitis), type of biologic drug (Infliximab, Adalimumab, Vedolizumab, or Ustekinumab) and disease activity, the reduction in IL-6 values was associated with a clinical response at 12 months of biological therapy (odds ratio (OR) = 4.75, 95% confidence interval (CI) 1.25–18.02, p = 0.022). In conclusion, the measurement of serum IL-6 in biologics-treated IBD patients may allow for the prediction of response to treatment at 12 months of therapy and thus may help with tailoring personalized treatment strategies.

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Section: Discussionsupporting

confidence: 82%

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Caviglia

Rosso

Stalla

et al. 2020

JCM

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“…In this way, antigens could easily be transported through the intestinal barrier leading to immune activation. Furthermore, Singh et al [94] found increased serum zonulin levels in IBS patients, comparable to those in celiac disease and a significant correlation between zonulin levels and bowel habit severity in IBS-D. Thus, serum or stool zonulin levels, an alternative non-invasive tool to investigate the integrity of the intestinal barrier, could also be considered a potential IBS molecular marker.…”

Section: When Things Get Inflamedmentioning

confidence: 99%

Irritable Bowel Syndrome between Molecular Approach and Clinical Expertise—Searching for Gap Fillers in the Oxidative Stress Way of Thinking

et al. 2020

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Irritable bowel syndrome (IBS) remains to date an intriguing functional gastrointestinal disorder. Recent studies described a multitude of exogenous factors that work together in IBS, gradually impairing intestinal lining cellular metabolism, including oxidative status balance, with or without a genetic background. Although the current biomarkers support the differentiation between IBS subtypes and other functional gastrointestinal disorder, they are mostly non-specific, referring to clinical, biochemical, and inflammatory imbalances. Since IBS could be also the result of deficient signaling pathways involving both gastrointestinal secretion and neuro-vegetative stimulation, IBS makes no exception from the oxidative hypothesis in the pathological mechanisms. Regarding the oxidative stress implication in IBS, the previous research efforts showed controversial results, with some animal models and patient studies reporting clear oxidative imbalance both on systemic and local levels, but still with no concrete evidence to point to a direct correlation between oxidative stress and IBS. Additionally, it seems that a major role could be also attributed to gut microbiota and their ability to shape our bodies and behaviors. Moreover, the genetic features study in IBS patients showed that several genetic similarities point to a possible correlation of IBS with affective spectrum disorders. Thus, we focus here the discussion on the assumption that IBS could in fact be more likely a stress-related disorder rather than a gastrointestinal one.

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“…To date, very few studies have investigated serum zonulin concentration in patients with IBS. Singh et al showed that serum zonulin levels in patients with IBS were higher compared with healthy controls and comparable to those with active coeliac disease [9]. Taking into account the results on serum zonulin concentration from previous studies conducted at our Center on IBD patients, we observed that serum zonulin concentration in patients with IBS-D was comparable to that found in patients with IBD (43.3 (95% CI 37.3-46.4) vs. 45.3 (95% CI 43.5-47.8) ng/mL, respectively) [30] and higher than those found in healthy controls (8.6 (95% CI 7.2-10.5) ng/mL) [8].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, higher serum zonulin levels were seen in patients with IBS compared to controls. Importantly, zonulin levels were directly correlated with the severity of bowel habits in patients with diarrhoea-predominant irritable bowel syndrome (IBS-D) [9].…”

Section: Introductionmentioning

confidence: 99%

Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with Bifidobacterium Longum ES1 for 8 or 12 Weeks: A Preliminary Report

Caviglia

Tucci

Pellicano

et al. 2020

JCM

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Bifidobacterium longum (B. longum) ES1 is a probiotic strain capable of modulating microbiome composition, anti-inflammatory activity and intestinal barrier function. We investigated the use of B. Longum ES1 in the treatment of patients with diarrhoea-predominant irritable bowel syndrome (IBS-D). Sixteen patients were treated for 8 or 12 weeks with B. Longum ES1 (1 × 109 CFU/day). Serum zonulin and cytokines were measured at baseline (T0) and at the end of therapy (T1). Clinical response to therapy was assessed by IBS Severity Scoring System. Interleukin (IL)-6, IL-8, IL-12p70 and tumor necrosis factor (TNF) α levels decreased from T0 to T1, irrespective of treatment duration (p < 0.05), while zonulin levels diminished only in patients treated for 12 weeks (p = 0.036). Clinical response was observed in 5/16 patients (31%): 4/8 (50%) treated for 12 weeks and 1/8 (13%) treated for 8 weeks. Abdominal pain improved only in patients treated for 12 weeks (5/8 vs. 0/8, p = 0.025), while stool consistency improved regardless of therapy duration (p < 0.001). In conclusion, the results of this pilot study showed, in IBS-D patients treated for 12 weeks with B. longum ES1, a reduction in the levels of pro-inflammatory cytokines, and intestinal permeability as well as an improvement in gastrointestinal symptoms, but further studies including a placebo-control group are necessary to prove a causal link.

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Serum zonulin is elevated in IBS and correlates with stool frequency in IBS‐D

Cited by 40 publications

References 35 publications

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

On-Treatment Decrease of Serum Interleukin-6 as a Predictor of Clinical Response to Biologic Therapy in Patients with Inflammatory Bowel Diseases

Irritable Bowel Syndrome between Molecular Approach and Clinical Expertise—Searching for Gap Fillers in the Oxidative Stress Way of Thinking

Clinical Response and Changes of Cytokines and Zonulin Levels in Patients with Diarrhoea-Predominant Irritable Bowel Syndrome Treated with Bifidobacterium Longum ES1 for 8 or 12 Weeks: A Preliminary Report

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