New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Sinagra, Emanuele; Morreale, Gaetano Cristian; Mohammadian, Ghazaleh; Fusco, G; Guarnotta, Valentina; Tomasello, Giovanni; Cappello, Francesco; Rossi, Francesca; Amvrosiadis, Georgios; Raimondo, Dario

doi:10.3748/wjg.v23.i36.6593

Cited by 46 publications

(45 citation statements)

References 233 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Low‐grade inflammation plays a vital role in IBS pathogenesis . In particular, an increased number of mast cells and a higher degree of mast cell activation have been reported in biopsies of IBS patients .…”

Section: Resultsmentioning

confidence: 99%

“…Low-grade inflammation plays a vital role in IBS pathogenesis. 38 In particular, an increased number of mast cells and a higher degree of mast cell activation have been reported in biopsies of IBS patients. 12,13 No morphological changes in the colon of MS rats were noted compared with the control group ( Figure 5A), and MS did not increase myeloperoxidase activity in the colon ( Figure 5B).…”

Section: Metformin Inhibits Colonic Low-grade Inflammation In Ms Ratsmentioning

confidence: 99%

See 1 more Smart Citation

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

Yang

Yao

et al. 2019

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background Intestinal barrier dysfunction is a key etiologic factor of irritable bowel syndrome (IBS). Metformin improves intestinal barrier function, although the underlying mechanism has yet to be fully explained. This study evaluates the protective effect of metformin on colonic barrier integrity and explores the underlying cellular mechanisms. Methods IBS‐like rats were induced by maternal separation. Metformin was administered daily by gavage at 08:30, and rat pups were then separated from their mother. Visceral hyperalgesia and depression‐like behaviors were evaluated by colorectal distension, sucrose preference tests, and forced swimming tests. Intestinal integrity was analyzed using sugar probes and transmission electron microscopy. Inflammatory factors and the levels of corticotropin‐releasing factor were assessed by PCR and ELISA. The number of mast cells was evaluated by toluidine blue staining. Protein expression and localization were determined using Western blot and immunochemistry. Key Results Metformin pretreatment (a) reduced visceral hypersensitivity to colorectal distension, immobility time and enhanced sucrose consumption; (b) decreased urine lactulose/mannitol ratio and sucralose output; (c) inhibited the dilation of tight junction and prevented claudin‐4 translocation; (d) inhibited mast cell activation and downregulated the expression of IL‐6, IL‐18, tryptase, PAR‐2, and ERK activation; (e) inhibited claudin‐4 phosphorylation at serine sites and interactions between clau‐4 and ZO‐1. Conclusions & Inferences Metformin may block mast cell activation to reduce PAR‐2 expression and subsequently inhibit ERK activation and clau‐4 phosphorylation at serine sites to normalize the interaction of clau‐4 and ZO‐1 and clau‐4 distribution. Metformin may be clinically beneficial for patients with IBS or IBS‐like symptoms.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Metformin Inhibits Colonic Low-grade Inflammation In Ms Ratsmentioning

confidence: 99%

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

Yang

Yao

et al. 2019

Neurogastroenterology Motil

View full text Add to dashboard Cite

show abstract

“…In all IBS patients, the serum PRDX1 (r = .335, P < .001) and TNF-α 16,33,[35][36][37] PRDX1 is associated with some tumors [21][22][23]38 and especially associated with colorectal cancer caused by chronic inflammation. 39,40 However, few studies have examined the relationship between PRDX1 and intestinal inflammation.…”

Section: Correlation Of Ibs-sss With Prdx1 and Tnf-α In Patients Wimentioning

confidence: 99%

Peroxiredoxin 1 as an inflammatory marker in diarrhea‐predominant and postinfectious irritable bowel syndrome

et al. 2019

Neurogastroenterology Motil

View full text Add to dashboard Cite

Background Low‐grade inflammation occurs in some patients with irritable bowel syndrome (IBS). However, the exact inflammatory markers of IBS and the relationship of these markers with IBS subtypes and symptoms are poorly defined. Peroxiredoxin 1 (PRDX1) plays an important role in inflammatory responses, including intestinal inflammation. We investigated whether PRDX1 is associated with the diagnosis, subtypes, and symptom severity of IBS. Methods A total of 177 IBS patients and 174 sex‐ and age‐matched healthy controls (HCs) were recruited. The PRDX1 levels in the sera and colonic mucosa of the participants were detected by enzyme‐linked immunosorbent assays and immunohistochemistry. The severity of IBS symptoms was assessed using the IBS Severity Scoring System (SSS) questionnaire. Results The PRDX1 levels in the sera (F = 71.81, P < .001) and colonic mucosa (F = 5.359, P < .001) of postinfectious (PI‐IBS) and diarrhea‐predominant IBS (IBS‐D) groups were significantly higher than those of the other three IBS subtypes and HC group. The PRDX1 level in the serum and colonic mucosa of IBS‐D (serum, P < .01, mucosa, P < .001) and PI‐IBS (serum, P < .05, mucosa, P < .001) groups with the most severe symptoms was significantly higher than that in the groups with mild and moderate symptoms. Correlation analysis revealed that in patients with IBS‐D (P < .001) and PI‐IBS (P < .05), the levels of PRDX1 and TNF‐α in sera had a significant positive correlation with IBS‐SSS. Conclusion Elevated PRDX1 in the serum and colon mucosa may be closely related to the progression of IBS (especially IBS‐D and PI‐IBS) and the expression of gastrointestinal symptoms.

show abstract

“…Although no studies have yet evaluated the efficacy of prucalopride in IBS-C (ref. 88 ). Renzapride is a full agonist for the 5HT type 4 receptor and an antagonist to 5HT type 2b and 5HT type 3 receptors.…”

Section: Serotonin Receptor Agonists and Antagonistsmentioning

confidence: 99%

“…Renzapride is a full agonist for the 5HT type 4 receptor and an antagonist to 5HT type 2b and 5HT type 3 receptors. Studies have shown that Renzapride is not superior to placebo in relieving IBS symptoms 88 .…”

Section: Serotonin Receptor Agonists and Antagonistsmentioning

confidence: 99%

Irritable bowel syndrome - from etiopathogenesis to therapy

Radovanović-Dinić¹,

Tešić-Rajković²,

Grgov³

et al. 2018

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

View full text Add to dashboard Cite

Irritable bowel syndrome (IBS) is a chronic and relapsing functional gastrointestinal disorder that affects 9-23% of the population across the world. Patients with IBS are often referred to gastroenterology, undergo various investigations, take various medicines, take time off work and have a poor quality of life. The pathophysiology of IBS is not yet completely understood and seems to be multifactorial. Many pathogenetic factors, in various combinations, and not all necessarily present in each patient, can play an important role. Discomfort or abdominal pain relieived by defacation, asociated with a change in stool form, is a typical clinical manifestation of IBS. Many factors, such as emotional stress and eating, may exacerbate the symptoms. A timely diagnosis of IBS is important so that treatment which will provide adequate symptomatic relief (diarrhoea, constipation, pain and boaring) can be introduced. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria IV is the current gold-standard for the diagnoses of IBS. Treatment of patients with IBS requires a multidisciplinary approach. Some patients respond well to non-pharmacological treatment, while others also require pharmacological treatment. This review will provide a summary of pathophysiology, diagnostic criteria and therapies for IBS.

show abstract

New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Cited by 46 publications

References 233 publications

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

Metformin prevents colonic barrier dysfunction by inhibiting mast cell activation in maternal separation‐induced IBS‐like rats

Peroxiredoxin 1 as an inflammatory marker in diarrhea‐predominant and postinfectious irritable bowel syndrome

Irritable bowel syndrome - from etiopathogenesis to therapy

Contact Info

Product

Resources

About