Fecal zonulin as a biomarker of increased intestinal permeability in patients with irritable bowel syndrome (narrative review and pilot study results)

Abstract Background Tong-Xie-Yao-Fang (TXYF) has been shown to be effective in diarrhoea-predominant irritable bowel syndrome (IBS-D) patients. However, the underlying mechanism remains to be clarified. The aim of this study was to investigate the efficacy and related mechanisms of TXYF in an IBS-D rat model. Methods The IBS-D rat model was established with 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. Then, IBS-D rats were divided into control, TXYF and rifaximin groups and treated intragastrically with normal saline, TXYF and rifaximin, respectively, for 14 days. The following indicators were measured before and after treatment: defecation frequency, faecal water content (FWC) and colorectal distension (CRD). Histopathological changes in the distal colon were observed after treatment. The expression of OCLN and ZO1 in the distal colon of IBS-D rats reflected the intestinal mucosal permeability, as measured by qRT-PCR, western blot, and enzyme-linked immunosorbent assays (ELISAs). The NF-κB and Notch signalling pathways and inflammation-related factors were investigated. Results After treatment with TXYF, the defecation frequency, FWC and CRD were significantly lower than those in the model group (P < 0.05). HE staining showed that colonic epithelial cells (CECs) in the IBS-D rats displayed significant oedema, impaired intestinal mucosal integrity and an increased influx of inflammatory cells. A significant reduction in granulocyte and CEC oedema was observed after the administration of TXYF and rifaximin compared to that of the model group and blank group (P < 0.05). TXYF significantly upregulated the expression of OCLN and ZO-1 and downregulated inflammation-related factors (IL-6, IL-1β, and TNF-α and the chemokine KC) in IBS-D rats compared to those in the model group rats (P < 0.05). In terms of the NF-κB and Notch signalling pathways, the expression of NICD, p-ERK, Hes-1 and p-P65 decreased significantly in the TXYF and rifaximin groups, while the expression of ATOH1 increased significantly compared to that in the model group (P < 0.05). Conclusion TXYF can effectively improve intestinal permeability and enhance intestinal mucosal barrier function, which may be related to inhibition of the inflammatory cascade and the NF-κB and Notch signalling pathways.

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Randomized, placebo-controlled, phase IV pilot study of ramosetron to evaluate the co-primary end points in male patients with irritable bowel syndrome with diarrhea

BioPsychoSocial Medicine ◽

10.1186/s13030-017-0093-9 ◽

2017 ◽

Vol 11 (1) ◽

Cited By ~ 3

Author(s):

Motoko Ida ◽

Akito Nishida ◽

Hiraku Akiho ◽

Yoshihiro Nakashima ◽

Kei Matsueda ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Pilot Study ◽

End Points ◽

Male Patients ◽

Irritable Bowel ◽

Phase Iv

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T1391 The Effect of Neurokinin-1 Receptor Antagonism On Central Responses to Visceral Pain in Irritable Bowel Syndrome (IBS): A Pilot Study

Gastroenterology ◽

10.1016/s0016-5085(08)62545-7 ◽

2008 ◽

Vol 134 (4) ◽

pp. A-545 ◽

Cited By ~ 2

Author(s):

Kirsten Tillisch ◽

Joshua A. Bueller ◽

Bruce D. Naliboff ◽

Brandall Y. Suyenobu ◽

Suzanne R. Smith ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Pilot Study ◽

Visceral Pain ◽

Receptor Antagonism ◽

Neurokinin 1 Receptor ◽

Neurokinin 1 ◽

Irritable Bowel

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Clinical Effects and Safety of Tongxieyaofang on Diarrhea Predominant Irritable Bowel Syndrome: A Meta-Analysis of Randomized Trails

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/4893876 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Yuhong Zhou ◽

Shutang Han ◽

Yamin He

Keyword(s):

Irritable Bowel Syndrome ◽

Large Scale ◽

Primary Outcome ◽

Meta Analysis ◽

Effective Rate ◽

Risk Of Bias ◽

Clinical Effects ◽

Randomized Controlled ◽

Study Results ◽

Irritable Bowel

Background. Tongxieyaofang (TXYF), a prescription originated from traditional Chinese medicine (TCM), has been widely used on treating Diarrhea Predominant Irritable Bowel Syndrome (IBS-D). The purpose of this meta-analysis was to investigate whether TXYF was effective and safe for IBS-D. Methods. We searched seven electronic databases including CENTRAL, MEDLINE, PubMed, CNKI, VIP, CBM, and Wanfang Data up to 26 July 2017. Randomized controlled trails (RCTs) were eligible, regardless of blinding. Risk of bias of included trials was evaluated according to the Cochrane Handbook. Results. The total number of participants analyzed in the meta-analysis was 3062, of which 1556 received TXYF, while 1506 received ordinary treatment. The primary outcome was clinical effective rate. Compared with conventional medication which included probiotics, pinaverium bromide, trimebutine, and Oryzanol, TXYF significantly improved the clinical effective rate (n=37, OR: 4.61; 95% CI: 3.67–5.78; P < 0.00001) and decreased the adverse events (n=10, OR: 0.26; 95% CI: 0.08–0.86; P = 0.03). There was not significant association with the score of abdominal pain, defecating frequency, fecal property, and total symptom. Conclusions. We suggested a moderate recommendation for TXYF on IBS-D, due to the fact that the risk of bias of the finally included trails was not high. Considering that all identified studies were not of high qualities and large samples, further rigorously designed and large scale RCTs were necessary to improve the applicability of our study results.

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