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Duodenal histology from IBS-like patients. Light microscopy (LM) histological images of duodenal biopsies in IBS-like disorders (H&E, magnification 20×). Intestinal villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis in uCD patients (a), restitutio ad integrum in tCD (b), no specific alterations found in WA (c), NCGS (d), Ni ACM (e), as well as in controls (f), Legend: uCD, untreated celiac disease; tCD, treated celiac disease; WA, wheat allergy; NCGS, non-celiac gluten sensitivity; Ni ACM, Nickel allergic contact mucositis; CTRL, controls.
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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...
Citations
... In the IBS group, this kind of adaptive response was not observed; in contrast, increased levels of cf-mtDNA were registered after the exercise program, so cf-mtDNA post-exercise values were significantly different between the two groups ( Figure 4B). It appears IBS per se, with its low-grade chronic inflammation [3,4,40], likely influences cf-mtDNA levels, possibly enhancing its release or impairing its removal. Indeed, the interplay between oxidative stress/inflammation and dysfunctional mitochondria has been highlighted in animal models of IBS [41,42]. ...
Irritable bowel syndrome (IBS) involves low-grade mucosal inflammation. Among the various approaches capable of managing the symptoms, physical activity is still under investigation. Despite its benefits, it promotes oxidative stress and inflammation. Mitochondria impacts gut disorders by releasing damage-associated molecular patterns, such as cell-free mtDNA (cf-mtDNA), which support inflammation. This study evaluated the effects of a 12-week walking program on the cf-mtDNA and DNase in 26 IBS and 17 non-IBS subjects. Pro- and anti-inflammatory cytokines were evaluated by ELISA. Digital droplet PCR was used to quantify cf-mtDNA; DNase activity was assessed using a single radial enzyme diffusion assay. PCR-RFLP was used to genotype DNASE1 rs1053874 SNP. Significantly lower IL-10 levels were found in IBS than in non-IBS individuals. Exercise reduced cf-mtDNA in non-IBS subjects but not in IBS patients. DNase activity did not correlate with the cf-mtDNA levels in IBS patients post-exercise, indicating imbalanced cf-mtDNA clearance. Different rs1053874 SNP frequencies were not found between groups. The study confirms the positive effects of regular moderate-intensity physical activity in healthy subjects and its role in cf-mtDNA release and clearance. Walking alone might not sufficiently reduce subclinical inflammation in IBS, based on imbalanced pro- and anti-inflammatory molecules. Prolonged programs are necessary to investigate their effects on inflammatory markers in IBS.
... Histological analysis of the intestinal barrier by light microscopy using hematoxylin and eosin (H&E) staining allow us to evaluate tissue integrity, the presence of mucosal ulcerations, and inflammatory infiltrate that could contribute to an increase in permeability [45]. Hematoxylin and eosin staining is a standard method applied for the histological observation of intestinal biopsies from patients with intestinal inflammatory diseases [46]. Similar to H&E staining, which is very useful for evaluating the gross morphology, electronic microscopy is a powerful method for the detailed observation of the architecture of junctional complexes in epithelial cells, with clinical implications for diagnosis and ther- ...
... Histological analysis of the intestinal barrier by light microscopy using hematoxylin and eosin (H&E) staining allow us to evaluate tissue integrity, the presence of mucosal ulcerations, and inflammatory infiltrate that could contribute to an increase in permeability [45]. Hematoxylin and eosin staining is a standard method applied for the histological observation of intestinal biopsies from patients with intestinal inflammatory diseases [46]. Similar to H&E staining, which is very useful for evaluating the gross morphology, electronic microscopy is a powerful method for the detailed observation of the architecture of junctional complexes in epithelial cells, with clinical implications for diagnosis and therapy. ...
... Similar to H&E staining, which is very useful for evaluating the gross morphology, electronic microscopy is a powerful method for the detailed observation of the architecture of junctional complexes in epithelial cells, with clinical implications for diagnosis and therapy. Electronic microscopy enables a detailed analysis of intestinal barrier damage, as reported in irritable-bowel-syndrome-like disorders [46]. Furthermore, the immunohistochemical (IHQ) method is the best choice to visualize the extent of the in situ location and distribution of TJPs, and the structural integrity of the intestinal epithelium. ...
The gut epithelium is a polarized monolayer that exhibits apical and basolateral membrane surfaces. Monolayer cell components are joined side by side via protein complexes known as tight junction proteins (TJPs), expressed at the most apical extreme of the basolateral membrane. The gut epithelium is a physical barrier that determinates intestinal permeability, referred to as the measurement of the transit of molecules from the intestinal lumen to the bloodstream or, conversely, from the blood to the gut lumen. TJPs play a role in the control of intestinal permeability that can be disrupted by stress through signal pathways triggered by the ligation of receptors with stress hormones like glucocorticoids. Preclinical studies conducted under in vitro and/or in vivo conditions have addressed underlying mechanisms that account for the impact of stress on gut permeability. These mechanisms may provide insights for novel therapeutic interventions in diseases in which stress is a risk factor, like irritable bowel syndrome. The focus of this study was to review, in an integrative context, the neuroendocrine effects of stress, with special emphasis on TJPs along with intestinal permeability.
... 1,2 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][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. ...
Background
Intestinal barrier dysfunction is a prevalent pathogenic factor underlying various disorders. Currently there is no effective resolution. Previous studies have reported the potential anti‐inflammatory properties of lidocaine and its ability to alleviate visceral hypersensitivity in individuals with irritable bowel syndrome (IBS). Therefore, our study will further verify the effect of lidocaine on intestinal barrier dysfunction in IBS and investigate the underlying mechanisms.
Methods
In this study, we investigated the role of lidocaine by assessing visceral hypersensitivity, body weight, inflammatory factors, fluorescein isothiocyanate‐dextran 4000 (FD4) flux, tight junctions (TJs) and spleen and thymus index in rats subjected to water avoidance stress (WAS) to mimic intestinal barrier dysfunction in IBS with and without lidocaine. In vitro, we investigated the role of corticotropin‐releasing hormone receptor 2 (CRHR2) in lidocaine‐treated Caco2 cells using small interfering RNA (siRNA) targeting CRHR2.
Key Results
In WAS rats, lidocaine significantly restored weight loss, damaged TJs, spleen index and thymus index and inhibited abdominal hypersensitivity as well as blood levels of markers indicating intestinal permeability, such as diamine oxidase (DAO), D‐lactic acid (D‐Lac) and lipopolysaccharide (LPS). Consequently, the leakage of FD4 flux from intestine was significantly attenuated in lidocaine group, and levels of intestinal inflammatory factors (IL‐1β, IFN‐γ, TNF‐α) were reduced. Interestingly, lidocaine significantly suppressed corticotropin‐releasing hormone (CRH) levels in lamina propria cells, while the CRH receptor CRHR2 was upregulated in intestinal epithelial cells. In vitro, lidocaine enhanced the expression of CRHR2 on Caco‐2 intestinal epithelial cells and restored disrupted TJs and the epithelial barrier caused by LPS. Conversely, these effects were diminished by a CRHR2 antagonist and siRNA‐CRHR2, suggesting that the protective effect of lidocaine depends on CRHR2.
Conclusions and Inferences
Lidocaine ameliorates intestinal barrier dysfunction in IBS by potentially modulating the expression of CRHR2 on intestinal epithelial cells.
... 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. ...
Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, significantly reducing the life quality of patients and negatively affecting public health in general. For a long period of time, this pathology has been studied exclusively from the view of gastrointestinal motility disorder and visceral hypersensitivity. At the same time, there is more and more evidence that a significant role in the disease pathogenesis can be played by the intestinal epithelial barrier dysfunction It has been established that the penetration of antigens from the intestinal lumen into the internal environment can contribute to excessive antigenic stimulation and the low degree inflammation in the intestinal mucosa, characteristic of IBS. In recent years, a huge number of studies have been devoted to the research concerning the phenomenon of "increased intestinal permeability" and the search for targeted molecules for pathogenetic therapy of IBS, a brief overview of which is presented in this article. Correction of dysbiotic disorders through the use of pro-, pre- and synbiotics, fecal transplantation and enhanced resistance of the intestinal mucosa by prescribing cytoprotectors seems promising KEYWORDS: mucosal barrier, irritable bowel syndrome, increased intestinal permeability, leaky gut syndrome, probiotics, prebiotics. FOR CITATION: Belyakov D.G., Gaus O.V., Gavrilenko D.A. Mucosal barrier role in the formation of irritable bowel syndrome as a potential target for disease therapy. Russian Medical Inquiry. 2022;6(8):458–463 (in Russ.). DOI: 10.32364/2587-6821-2022-6-8-458-463.
Chronic inflammatory enteropathies (CIEs) are an important group of diseases in dogs and involve complex pathogenetic aspects. Endoscopy and histopathology are vital for documenting the disease but are less useful for subclassifying CIEs and predicting the response to treatment. However, healing of the mucosal disease process (deep remission) and ultrastructural evaluation of the mucosa have received little attention in canine CIE. Given that canine CIE shares many similarities with inflammatory bowel diseases (IBDs) in human patients—and presents a good spontaneous disease model for human IBD—this perspective article evaluates the literature on ultrastructural lesions in canine CIE and human IBD and offers future directions for the study of ultrastructural mucosal lesions in canine CIE. Such lesions might have a higher sensitivity of detection than structural changes revealed upon light microscopy and may even precede or remain after the resolution of the clinical signs and histologic lesions.
Background Intestinal epithelial barrier dysfunction (“leaky gut syndrome”, LGS) is thought to play a major role in the pathogenesis of disorders of the gut brain axis. Endoscopic confocal laser endomicroscopy (eCLE) is an objective measure to test duodenal permeability. We applied this technique in patients with functional gastrointestinal symptoms and food intolerance to characterize the proportion of patients with LGS.
Material and Methods In an observational study, we evaluated 85 patients with functional gastrointestinal symptoms and food intolerance. Gastrointestinal symptoms were classified according to Rom IV into functional abdominal pain (FAP), irritable bowel syndrome (IBS), irritable bowel syndrome diarrhea dominant (IBS-D), irritable bowel syndrome constipation dominant (IBS-C), irritable bowel syndrome with mixed stool (IBS-M), functional abdominal bloating (FAB), functional diarrhea (FD) and unclassified (NC). During eCLE, spontaneous transfer of intravenously applied fluorescein into duodenal lumen (LGS) and following duodenal food challenge (DFC) were analyzed. Blood analysis comprised parameters of mast cell function, histology of duodenal mucosal biopsies analysis of mucosal inflammation, intraepithelial lymphocytes (IELs) as well as number, distribution and morphology of mast cells.
Results 24 patients (9 IBS, 9 FAP, 3 FAB, 1 FD, 2 NC), showed LGS, 50 patients (14 IBS-D, 4 IBS-C, 3 IBS-M, 23 FAP, 3 FAB, 3 NC) had no LGS but responded to DFC and 11 patients (6 NC, 3 FAP, 1 FAB, 1 FD) had no LGS and no response to DFC. The proportion of subgroups with/or without spontaneous leakage of fluorescein (+LGS/-LGS) were IBS-LGS/IBS+LGS 67%/33%, FAP-LGS/FAP+LGS 72%/28%,FAB-LGS/FAB+LGS 50%/50%, NC-LGS/NC+LGS 60%/40%. Subgroup analysis revealed no significant differences for all parameters tested.
Conclusion As a proof of concept, the results of our study indicate that eCLE is a clinical useful tool to evaluate patients with disorders of the gut brain axis and those suspicious of LGS. However, the clinical significance of LGS remains unclear. The study should be an incentive to perform a randomized study including healthy controls.
The interaction between mitochondria and gut microbiota plays a critical role in intestinal physiological homeostasis. In this kind of homeostasis, intestinal epithelial hypoxia helps microbiota to be dominated by obligate anaerobes, who provide their benefit metabolites for the host, such as short chain fatty acids (SCFAs). In addition, emerging studies suggest that microbial signals to the mitochondria of intestinal epithelial cells (IECs) could alter mitochondrial ultrastructure and its metabolic function, induce inflammasome activation and disrupt epithelial hypoxia. Conditions that alter the mitochondria could lead to intestinal epithelium inflammation and oxygenation, both of which would drive an expansion of facultative anaerobes and exacerbate the imbalance of mitochondria-microbiota crosstalk. This phenomenon has proved to be associated with the pathogenesis of gastrointestinal (GI) diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC). Therefore, in this review, we summarized the recent process on the interaction between mitochondria of IECs and gut microbiota in the case of both GI physiological homeostasis and diseases, and potential therapeutic interventions targeting mitochondria-microbiota crosstalk in GI diseases.
