scholarly journals Qingchang Wenzhong Decoction Attenuates DSS-Induced Colitis in Rats by Reducing Inflammation and Improving Intestinal Barrier Function via Upregulating the MSP/RON Signalling Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Tangyou Mao ◽  
Junxiang Li ◽  
Lijuan Liu ◽  
Weihan Zhao ◽  
Yuyue Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Inflammatory Response ◽  
Barrier Function ◽  
Clinical Symptoms ◽  
Quantitative Polymerase Chain Reaction ◽  
Intestinal Barrier ◽  
Signalling Pathway ◽  
Intestinal Barrier Function ◽  
Dextran Sulphate ◽  
Dextran Sulphate Sodium

Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease for which an effective treatment is lacking. Our previous study found that Qingchang Wenzhong Decoction (QCWZD) can significantly improve the clinical symptoms of UC and ameliorate dextran sulphate sodium- (DSS-) induced ulcerative colitis in rats by downregulating the IP10/CXCR3 axis–mediated inflammatory response. The purpose of the present study was to further explore the mechanism of QCWZD for UC in rats models, which were established by 7-day administration of 4.5% dextran sulphate sodium solution. QCWZD was administered daily for 7 days; then we determined the serum macrophage-stimulating protein concentration (MSP) and recepteur d’origine nantais (RON) expression and its downstream proteins (protein kinase B [Akt], phosphorylated [p] Akt, occludin, zona occluden- [ZO-] 1, and claudin-2) in colon tissue using Western blotting and quantitative polymerase chain reaction. In DSS-induced UC, QCWZD significantly alleviated colitis-associated inflammation, upregulated serum MSP expression and RON expression in the colon, reduced the pAkt levels, promoted colonic occluding and ZO-1 expression, and depressed claudin-2 expression. In conclusion, the MSP/RON signalling pathway plays an important role in the pathogenesis of UC by involving the inflammatory response and improving intestinal barrier function. QCWZD appears to attenuate DSS-induced UC in rats by upregulating the MSP/RON signalling pathway.

scholarly journals Gut Microbiota-Mediated NLRP12 Expression Drives the Attenuation of Dextran Sulphate Sodium-Induced Ulcerative Colitis by Qingchang Wenzhong Decoction

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Zhongmei Sun ◽  
Wenjing Pei ◽  
Yi Guo ◽  
Zhibin Wang ◽  
Rui Shi ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Clinical Symptoms ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Dextran Sulphate ◽  
16S Rrna Analysis ◽  
Dextran Sulphate Sodium ◽  
Regulatory Effects ◽  
The Relationship

Qingchang Wenzhong Decoction (QCWZD) is a newly developed, effective traditional Chinese herbal formulation for ulcerative colitis (UC). In earlier studies, we found that QCWZD could relieve the clinical symptoms of UC patients, reduce inflammation, and improve the intestinal barrier function in dextran sulphate sodium (DSS)-induced UC rats. However, the relationship between QCWZD and the gut microbiota in colitis was not clarified. In this study, we established a rat model of DSS-induced UC and then investigated the regulatory effects of QCWZD on the gut microbiota using 16S rRNA analysis. We also determined the expression of NLRP12 after QCWZD administration. Our findings suggested that QCWZD administration could modulate gut microbiota composition and selectively promote the protective strains such asButyricimonas,Blautia,andOdoribacter,whereas the enteric pathogens includingClostridiumandDoreawere significantly reduced after QCWZD treatment. It is noteworthy that QCWZD administration was identified to promote gut microbiota-mediated NLRP12 expression by inhibiting the activity of the TLR4/Blimp-1 axis. In conclusion, our study supports the potential of QCWZD administration as a beneficial therapeutic strategy for UC.

scholarly journals Mo1112 – Microrna-24 is Overexpressed in Ulcerative Colitis and Significantly Affects Intestinal Barrier Function

2019 ◽  
Vol 156 (6) ◽  
pp. S-710
Author(s):  
Artin Soroosh ◽  
Carl R. Rankin ◽  
Zulfiqar A. Lokhandwala ◽  
Christos Polytarchou ◽  
Charalabos Pothoulakis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function

Bin1 Targeted Immunotherapy Alters the Status of the Enteric Neurons and the Microbiome during Ulcerative Colitis Treatment

2020 ◽  
Author(s):  
Sunil Thomas ◽  
Giancarlo Mercogliano ◽  
George Prendergast
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiome ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Enteric Neurons ◽  
Intestinal Barrier Function ◽  
Common Chronic Disease ◽  
The Status ◽  
Genus Lactobacillus ◽  
High Level

Ulcerative colitis (UC) is a common chronic disease of the large intestine. Current anti-inflammatory drugs prescribed to treat this disease have limited utility due to significant side-effects. Thus, immunotherapies for UC treatment are still sought. In the DSS mouse model of UC, we recently demonstrated that systemic administration of the Bin1 monoclonal antibody 99D (Bin1 mAb) developed in our laboratory was sufficient to reinforce intestinal barrier function and preserve an intact colonic mucosa, compared to control subjects which displayed severe mucosal lesions, high-level neutrophil and lymphocyte infiltration of mucosal and submucosal areas, and loss of crypts. Here we report effects of Bin1 mAb on colonic neurons and the gut microbiome that correlate with the benefits of treatment. In the DSS model, we found that induction of UC was associated with disintegration of enteric neurons and elevated levels of glial cells, which translocated to the muscularis at distinct sites. Further, we characterized an altered gut microbiome in DSS treated mice associated with pathogenic proinflammatory characters. Both of these features of UC induction were normalized by Bin1 mAb treatment. With regard to microbiome changes, we observed in particular that Firmicutes were eliminated by UC induction and that Bin1 mAb treatment restored this phylum including the genus Lactobacillus and Akkermansia as beneficial microorganisms. Overall, our findings suggest that the intestinal barrier function restored by Bin1 immunotherapy in the DSS model of UC is associated with a preservation of enteric neurons and an improvement in the gut microbiome, contributing overall to a healthy intestinal tract.

scholarly journals Fish oil enhances intestinal barrier function and inhibits corticotropin-releasing hormone/corticotropin-releasing hormone receptor 1 signalling pathway in weaned pigs after lipopolysaccharide challenge

2016 ◽  
Vol 115 (11) ◽  
pp. 1947-1957 ◽  
Author(s):  
Huiling Zhu ◽  
Yulan Liu ◽  
Shaokui Chen ◽  
Xiuying Wang ◽  
Dingan Pi ◽  
...  
Keyword(s):  
Mast Cell ◽  
Fish Oil ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Signalling Pathway ◽  
Intestinal Barrier Function ◽  
Signalling Pathways ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Fish Oil Supplementation

AbstractStress induces injury in intestinal barrier function in piglets. Long-chain n-3 PUFA have been shown to exhibit potential immunomodulatory and barrier protective effects in animal models and clinical trials. In addition, corticotropin-releasing hormone (CRH)/CRH receptor (CRHR) signalling pathways play an important role in stress-induced alterations of intestinal barrier function. We hypothesised that fish oil could affect intestinal barrier function and CRH/CRHR signalling pathways. In total, thirty-two weaned pigs were allocated to one of four treatments. The experiment consisted of a 2×2 factorial design, and the main factors included immunological challenge (saline or lipopolysaccharide (LPS)) and diet (5 % maize oil or 5 % fish oil). On d 19 of the trial, piglets were treated with saline or LPS. At 4 h after injection, all pigs were killed, and the mesenteric lymph nodes (MLN), liver, spleen and intestinal samples were collected. Fish oil decreased bacterial translocation incidence and the number of translocated micro-organisms in the MLN. Fish oil increased intestinal claudin-1 protein relative concentration and villus height, as well as improved the intestinal morphology. In addition, fish oil supplementation increased intestinal intraepithelial lymphocyte number and prevented elevations in intestinal mast cell and neutrophil numbers induced by LPS challenge. Moreover, fish oil tended to decrease the mRNA expression of intestinal CRHR1, CRH and glucocorticoid receptors. These results suggest that fish oil supplementation improves intestinal barrier function and inhibits CRH/CRHR1 signalling pathway and mast cell tissue density.

scholarly journals Dietary Fiber Ameliorates Lipopolysaccharide-Induced Intestinal Barrier Function Damage in Piglets by Modulation of Intestinal Microbiome

mSystems ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Xiao Sun ◽  
Yalei Cui ◽  
Yingying Su ◽  
Zimin Gao ◽  
Xinying Diao ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Growth Performance ◽  
Proinflammatory Cytokines ◽  
Barrier Function ◽  
Intestinal Microflora ◽  
Intestinal Barrier ◽  
Intestinal Morphology ◽  
Intestinal Barrier Function ◽  
Tnf Α

ABSTRACT Weaning of piglets is accompanied by intestinal inflammation, impaired intestinal barrier function, and intestinal microflora disorder. Regulating intestinal microflora structure can directly or indirectly affect intestinal health and host growth and development. However, whether dietary fiber (DF) affects the inflammatory response and barrier function by affecting the intestinal microflora and its metabolites is unclear. In this study, we investigated the role of intestinal microflora in relieving immune stress and maintaining homeostasis using piglets with lipopolysaccharide (LPS)-induced intestinal injury as a model. DF improved intestinal morphology and barrier function, inhibited the expression of inflammatory signal pathways (Toll-like receptor 2 [TLR2], TLR4, and NF-κB) and proinflammatory cytokines (interleukin 1β [IL-1β], IL-6, and tumor necrosis factor alpha [TNF-α]), and upregulated the expression of barrier-related genes (encoding claudin-1, occludin, and ZO-1). The contents of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and the activity of diamine oxidase in plasma were decreased. Meanwhile, DF had a strong effect on the composition and function of intestinal microflora at different taxonomic levels, the relative abundances of cellulolytic bacteria and anti-inflammatory bacteria were increased, and the concentrations of propionate, butyrate, and total short-chain fatty acids (SCFAs) in intestinal contents were increased. In addition, the correlation analysis also revealed the potential relationship between metabolites and certain intestinal microflora, as well as the relationship between metabolites and intestinal morphology, intestinal gene expression, and plasma cytokine levels. These results indicate that DF improves intestinal barrier function, in part, by altering intestinal microbiota composition and increasing the synthesis of SCFAs, which subsequently alleviate local and systemic inflammation. IMPORTANCE Adding DF to the diet of LPS-challenged piglets alleviated intestinal and systemic inflammation, improved intestinal barrier function, and ultimately alleviated the growth retardation of piglets. In addition, the addition of DF significantly increased the relative abundance of SCFA-producing bacteria and the production of SCFAs. We believe that the improvement of growth performance of piglets with LPS-induced injury can be attributed to the beneficial effects of DF on intestinal microflora and SCFAs, which reduced the inflammatory response in piglets, improving intestinal barrier function and enhancing body health. These research results provide a theoretical basis and guidance for the use of specific fiber sources in the diet to improve intestinal health and growth performance of piglets and thus alleviate weaning stress. Our data also provide insights for studying the role of DF in regulating gastrointestinal function in human infants.

scholarly journals Expression of tricellular tight junction proteins and the paracellular macromolecule barrier are recovered in remission of ulcerative colitis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jia-Chen E. Hu ◽  
Franziska Weiß ◽  
Christian Bojarski ◽  
Federica Branchi ◽  
Jörg-Dieter Schulzke ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Benjamin Franklin ◽  
Clinical Appearance ◽  
Ussing Chambers ◽  
Junction Protein ◽  
Underlying Mechanisms

Abstract Background Ulcerative colitis (UC) has a relapsing and remitting pattern, wherein the underlying mechanisms of the relapse might involve an enhanced uptake of luminal antigens which stimulate the immune response. The tricellular tight junction protein, tricellulin, takes charge of preventing paracellular passage of macromolecules. It is characterized by downregulated expression in active UC and its correct localization is regulated by angulins. We thus analyzed the tricellulin and angulin expression as well as intestinal barrier function and aimed to determine the role of tricellulin in the mechanisms of relapse. Methods Colon biopsies were collected from controls and UC patients who underwent colonoscopy at the central endoscopy department of Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin. Remission of UC was defined basing on the clinical appearance and a normal Mayo endoscopic subscore. Intestinal barrier function was evaluated by electrophysiological and paracellular flux measurements on biopsies mounted in Ussing chambers. Results The downregulated tricellulin expression in active UC was recovered in remission UC to control values. Likewise, angulins were in remission UC at the same levels as in controls. Also, the epithelial resistance which was decreased in active UC was restored in remission to the same range as in controls, along with the unaltered paracellular permeabilities for fluorescein and FITC-dextran 4 kDa. Conclusions In remission of UC, tricellulin expression level as well as intestinal barrier functions were restored to normal, after they were impaired in active UC. This points toward a re-sealing of the impaired tricellular paracellular pathway and abated uptake of antigens to normal rates in remission of UC.

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