New Insights into Intestinal Permeability in Irritable Bowel Syndrome-Like Disorders: Histological and Ultrastructural Findings of Duodenal Biopsies

Abstract

Background and Aim: Diarrhea, abdominal pain, and bloating are frequent in irritable bowel syndrome (IBS)-like disorders, although little is known about their intestinal ultrastructural alterations. The aim of the present study was to study duodenal biopsies from IBS-like patients to find ultrastructural alterations. Materials and Methods: Study design: descriptive comparative pilot study. Thirty outpatients (9 male and 21 female; median age 37.7 years; range, 20 to 65 years) complaining of IBS-like symptoms were enrolled between January 2015 to May 2019 and were divided into 6 groups, each equally consisting of 5 patients: (A) untreated celiac disease (uCD); (B) treated celiac disease (tCD); (C) wheat allergy (WA); (D) Non-celiac gluten sensitivity (NCGS); (E) Nickel allergic contact mucositis (Ni ACM); (F) controls affected by GERD. Transmission electron microscopy (TEM) morphological characteristics were: microvilli length, intermicrovillar distance, junctional complexes (JC) gap width, autophagic bodies, apoptosis, altered mitochondria, lipid/chylomicron droplets, and mast cells. Regarding JC, we focused on tight junctions (TJ), adherens junctions (AJ), and desmosomes. Results: Major alterations in microvilli length and intermicrovillar distance have been observed in the subjects affected by uCD. Microvilli of tCD patients showed marked recovery after adequate GFD, although not comparable to controls. Intermediate microvillar alterations were instead observed in NCGS and Ni ACM, while characteristics of WA subjects appeared more similar to tCD. Regarding JC, TJ did not show significant differences between all groups studied, including controls. The AJ were significantly more dilated in all groups compared to controls, while no significant differences were found between the pathological groups. The distance between desmosomes was greater in uCD, NCGS, and Ni ACM than in tCD, WA, and controls. Finally, intracellular alterations have been detected in most of the groups studied although they seemed more unspecific. Conclusions: TEM analysis confirmed damages to the intestinal barrier and defense mechanisms by enterocytes in IBS-like patients, probably linked to low-grade inflammation or adverse reactions triggered by food allergens, heavy metals, or other unknown. On the other hand, our study needs confirmation and further investigations with larger populations to facilitate diagnosis, therapy, and prevention of IBS-like disorders in the future.

Endoscopic laser endomicroscopy and “leaky gut” in patients with functional gastrointestinal symptoms and food intolerance

“…Intestinal epithelial barrier dysfunction and increased permeability have been described in disorders of the gut brain axis [1,2,3]. A tight junction barrier defect that enhances disease progression has been suggested in postinfectious IBS and FD [11,14,15,16,17,20]. In a recent paper, Noikow et al [14] reported duodenal mucosal probe based confocal laser endomicroscopy (pCLE) abnormalities in patients with FD.…”

“…It is known that low-grade inflammation exists in the duodenum of patients with FD and IBS [4,5,6,7,8,9,10,11]. The intestinal hyperpermeability may enable noxious microorganisms, their toxins and antigens to "leak" into the duodenal wall and bloodstream and consequently trigger reactions in both gastrointestinal and non-gastrointestinal diseases [12].…”

Mucosal barrier role in the formation of irritable bowel syndrome as a potential target for disease therapy

“…В настоящее время нарушение функции мукозального барьера и повышение кишечной проницаемости считается одним из основных патогенетических механизмов развития СРК [27]. Известно, что проникновение антигенов из просвета кишечника во внутреннюю среду организма может способствовать чрезмерной антигенной стимуляции и формированию воспаления низкой степени активности в слизистой оболочке кишечника, характерного для СРК.…”

Lidocaine ameliorates intestinal barrier dysfunction in irritable bowel syndrome by modulating corticotropin‐releasing hormone receptor 2

“…[3][4][5] Additionally, increasing evidence suggests enhanced intestinal permeability, dysregulated microbiome and changes in immune function contribute to IBS. [6][7][8] Intestinal mucosa damage and dysbiosis of the intestinal microflora lead to the permeation of harmful substances such as pathogenic bacteria or antigens into the bloodstream or other organs, contributing to the development or exacerbation of multiple organ dysfunction and inflammation. 9,10 While immunomodulators and antibiotics are commonly used to alleviate symptoms, their adverse side effects and high rates of drug resistance impact patients' quality of life.…”

“…Studies have reported that the symptoms of IBS involve dysfunction of interactions between central and peripheral nervous system factors, low‐grade inflammation, and intestinal infections 3–5 . Additionally, increasing evidence suggests enhanced intestinal permeability, dysregulated microbiome and changes in immune function contribute to IBS 6–8 . Intestinal mucosa damage and dysbiosis of the intestinal microflora lead to the permeation of harmful substances such as pathogenic bacteria or antigens into the bloodstream or other organs, contributing to the development or exacerbation of multiple organ dysfunction and inflammation 9,10 .…”