scholarly journals Acute Effects of Butyrate on Induced Hyperpermeability and Tight Junction Protein Expression in Human Colonic Tissues

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 766
Author(s):  
Mathias W. Tabat ◽  
Tatiana M. Marques ◽  
Malin Markgren ◽  
Liza Löfvendahl ◽  
Robert J. Brummer ◽  
...  
Keyword(s):  
Tight Junction ◽  
Ex Vivo ◽  
Ussing Chamber ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Healthy Humans ◽  
Junction Protein ◽  
Pre Treatment ◽  
Related Proteins

Intact intestinal barrier function is essential for maintaining intestinal homeostasis. A dysfunctional intestinal barrier can lead to local and systemic inflammation through translocation of luminal antigens and has been associated with a range of health disorders. Butyrate, a short-chain fatty acid derived from microbial fermentation of dietary fibers in the colon, has been described as an intestinal barrier-strengthening agent, although mainly by using in vitro and animal models. This study aimed to investigate butyrate’s ability to prevent intestinal hyperpermeability, induced by the mast cell degranulator Compound 48/80 (C48/80), in human colonic tissues. Colonic biopsies were collected from 16 healthy subjects and intestinal permeability was assessed by Ussing chamber experiments. Furthermore, the expression levels of tight junction-related proteins were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Pre-treatment with 5 mM butyrate or 25 mM butyrate did not protect the colonic tissue against induced paracellular or transcellular hyperpermeability, measured by FITC-dextran and horseradish peroxidase passage, respectively. Biopsies treated with 25 mM butyrate prior to stimulation with C48/80 showed a reduced expression of claudin 1. In conclusion, this translational ex vivo study did not demonstrate an acute protective effect of butyrate against a chemical insult to the intestinal barrier in healthy humans.

scholarly journals Exploring Effects of Chitosan Oligosaccharides on the DSS-Induced Intestinal Barrier Impairment In Vitro and In Vivo

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2199
Author(s):  
Yujie Wang ◽  
Rong Wen ◽  
Dongdong Liu ◽  
Chen Zhang ◽  
Zhuo A. Wang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Structural Characteristics ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Chitosan Oligosaccharide ◽  
Intestinal Epithelial ◽  
Mucus Layer ◽  
Intestinal Mucus ◽  
Epithelial Tight Junction

Intestinal barrier dysfunction is an essential pathological change in inflammatory bowel disease (IBD). The mucus layer and the intestinal epithelial tight junction act together to maintain barrier integrity. Studies showed that chitosan oligosaccharide (COS) had a positive effect on gut health, effectively protecting the intestinal barrier in IBD. However, these studies usually focused on its impact on the intestinal epithelial tight junction. The influence of COS on the intestinal mucus layer is still poorly understood. In this study, we explored the effect of COS on intestinal mucus in vitro using human colonic mucus-secreted HT-29 cells. COS relieved DSS (dextran sulfate sodium)-induced mucus defects. Additionally, the structural characteristics of COS greatly influenced this activity. Finally, we evaluated the protective effect of COS on intestinal barrier function in mice with DSS-induced colitis. The results indicated that COS could manipulate intestinal mucus production, which likely contributed to its intestinal protective effects.

PSX-A-9 Late-Breaking: Effects of farm noise on ileum intestinal barrier function of pullets

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 367-367
Author(s):  
Chun Li ◽  
Runxiang Zhang ◽  
Hanlin Yu ◽  
Yanru Feng ◽  
Jianhong Li ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Animal Husbandry ◽  
Low Noise ◽  
Intestinal Barrier Function ◽  
Control Group ◽  
Tissue Samples ◽  
Real Time Quantitative Pcr ◽  
Junction Protein ◽  
Related Proteins

Abstract Noise is a potential but not negligible environmental factor in animal husbandry. To investigate the effects of farm noise on intestinal barrier function of pullets, 336 Hailanhe pullets aged 1 day were randomly divided into 3 groups: control group (CON), low noise group (LN), high noise group (HN). LN group and HN group were exposed to noise respectively at 65–75 dB and 85–95 dB, the average and the range of the highest loudness of noise in laying hens’ farms for 6h every day (7:00-19:00, hourly intervals for one hour) and lasted 4 weeks. Non additional noise addition in CON group, noise loudness of which was less than 40dB. 6 birds were randomly chosen form each group after every week of noise stimulation for ileum tissue samples. Hematoxylin-eosin stain (HE stain), immunofluorescence, and real-time quantitative PCR (qRT-PCR) were used to determine changes in ileum structure, expression of intestinal barrier related proteins and mRNAs and HSPs. Results shown that 1 week and 2 weeks after noise exposed inflammatory cell infiltration reduced, the expression of intestinal barrier related proteins (Occludin, Mucin2 and ZO-1) and mRNAs (Claudin-1, Claudin-4, E-cadherin, Occludin, Mucin2, ZO-1 and ZO-2) were significantly increased (P < 0.05), the mRNA expression of HSPs decreased (P < 0.05) or have no significate changes (P > 0.05). After 4 weeks of noise treatment, the expression of mRNAs of intestinal tight junction protein and mucin, HSPs were significantly decreased (P < 0.05). There was no difference between the LN and HN groups on those indicators (P > 0.05). The study indicates that noise at 65-75dB and 85-95dB does not cause stress to ileum of pullets while promote the development of intestinal barrier of chicks within 2 weeks maybe by mild stimulation and birds restored to balance due to habitualization after 4 weeks of noise treatment.

Zinc strengthens the jejunal barrier by reversibly tightening the paracellular route

2017 ◽  
Vol 313 (6) ◽  
pp. G537-G548 ◽  
Author(s):  
Silke S. Zakrzewski ◽  
Michael Fromm ◽  
Jörg D. Schulzke ◽  
Dorothee Günzel
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Secretory Diarrhea ◽  
Intestinal Barrier Function ◽  
Epithelial Barrier ◽  
Gastrointestinal Infections ◽  
Apical Side

During the postweaning period, piglets are prone to gastrointestinal infections. The resulting impairment of intestinal barrier function may cause diarrhea associated with growth retardation or even death of piglets. Orally applied Zn is commonly used to prevent and treat diarrhea, but its mode of action still needs to be elucidated. To analyze the molecular mechanism whereby Zn acts on porcine intestinal barrier function, ex vivo studies on piglet jejunum and accompanying in vitro studies on a porcine jejunal epithelial cell line, IPEC-J2/PS, were performed with electrophysiological tools. Feeding pharmacological Zn doses exerted no significant electrophysiologically ascertainable short- and long-term effects on jejunal barrier function ex vivo. However, in IPEC-J2/PS, basolateral Zn was cytotoxic since its application caused a release of lactate dehydrogenase and an irreversible breakdown of the epithelial barrier. In contrast, apical Zn application caused an immediate increase in paracellular resistance and a decrease in permeability to the paracellular marker fluorescein, reflecting overall barrier strengthening in vitro. Apical effects were fully reversible upon washout. This indicates that Zn supplemented to feed was completely washed out during ex vivo jejunum preparation. We conclude that there is no evidence for long-term barrier effects through prophylactic Zn supplementation and that extracellular Zn acts acutely and reversibly from the apical side via tightening the paracellular route, thus counteracting leak-flux diarrhea. NEW & NOTEWORTHY Therapeutically administered Zn successfully treats diarrhea in veterinary and human medicine. Here we present data that Zn strengthens the porcine jejunal epithelial barrier by reversibly tightening the paracellular route for inorganic ions and small solutes. Acute or long-lasting Zn effects on transcellular transport (Cl− secretion) were not detected. We therefore conclude that Zn is useful for acutely treating leak-flux diarrhea rather than secretory diarrhea. Suitability as prophylactic feed supplement, however, is questionable.

scholarly journals Caprate Modulates Intestinal Barrier Function in Porcine Peyer’s Patch Follicle-Associated Epithelium

2019 ◽  
Vol 20 (6) ◽  
pp. 1418 ◽  
Author(s):  
Judith Radloff ◽  
Valeria Cornelius ◽  
Alexander G. Markov ◽  
Salah Amasheh
Keyword(s):  
Barrier Function ◽  
Ex Vivo ◽  
Intestinal Barrier ◽  
Barrier Properties ◽  
Food Allergies ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Food Component ◽  
Follicle Associated Epithelium

Background: Many food components influence intestinal epithelial barrier properties and might therefore also affect susceptibility to the development of food allergies. Such allergies are triggered by increased antibody production initiated in Peyer’s patches (PP). Usually, the presentation of antigens in the lumen of the gut to the immune cells of the PP is strongly regulated by the follicle-associated epithelium (FAE) that covers the PP. As the food component caprate has been shown to impede barrier properties in villous epithelium, we hypothesized that caprate also affects the barrier function of the PP FAE, thereby possibly contributing a risk factor for the development of food allergies. Methods: In this study, we have focused on the effects of caprate on the barrier function of PP, employing in vitro and ex vivo experimental setups to investigate functional and molecular barrier properties. Incubation with caprate induced an increase of transepithelial resistance, and a marked increase of permeability for the paracellular marker fluorescein in porcine PP to 180% of control values. These effects are in accordance with changes in the expression levels of the barrier-forming tight junction proteins tricellulin and claudin-5. Conclusions: This barrier-affecting mechanism could be involved in the initial steps of a food allergy, since it might trigger unregulated contact of the gut lumen with antigens.

scholarly journals Tight Junction–associated MARVEL Proteins MarvelD3, Tricellulin, and Occludin Have Distinct but Overlapping Functions

2010 ◽  
Vol 21 (7) ◽  
pp. 1200-1213 ◽  
Author(s):  
David R. Raleigh ◽  
Amanda M. Marchiando ◽  
Yong Zhang ◽  
Le Shen ◽  
Hiroyuki Sasaki ◽  
...  
Keyword(s):  
Tight Junction ◽  
Protein Interactions ◽  
Electron Microscopic Examination ◽  
Electron Microscopic ◽  
Junction Protein ◽  
Tight Junction Regulation ◽  
Sirna Knockdown ◽  
Related Proteins

In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction–associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.

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.

scholarly journals Leptin Downregulates Angulin-1 in Active Crohn’s Disease via STAT3

2020 ◽  
Vol 21 (21) ◽  
pp. 7824
Author(s):  
Jia-Chen Hu ◽  
Christian Bojarski ◽  
Federica Branchi ◽  
Michael Fromm ◽  
Susanne Krug
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Fat Tissue ◽  
Jak2 Inhibitor ◽  
Junction Protein ◽  
Underlying Mechanisms

Crohn’s disease (CD) has an altered intestinal barrier function, yet the underlying mechanisms remain to be disclosed. The tricellular tight junction protein tricellulin is involved in the maintenance of the paracellular macromolecule barrier and features an unchanged expression level in CD but a shifted localization. As angulins are known to regulate the localization of tricellulin, we hypothesized the involvement of angulins in CD. Using human biopsies, we found angulin-1 was downregulated in active CD compared with both controls and CD in remission. In T84 and Caco-2 monolayers, leptin, a cytokine secreted by fat tissue and affected in CD, decreased angulin-1 expression. This effect was completely blocked by STAT3 inhibitors, Stattic and WP1066, but only partially by JAK2 inhibitor AG490. The effect of leptin was also seen at a functional level as we observed in Caco-2 cells an increased permeability for FITC-dextran 4 kDa indicating an impaired barrier against macromolecule uptake. In conclusion, we were able to show that in active CD angulin-1 expression is downregulated, which leads to increased macromolecule permeability and is inducible by leptin via STAT3. This suggests that angulin-1 and leptin secretion are potential targets for intervention in CD to restore the impaired intestinal barrier.

scholarly journals Glutamine supplementation improves intestinal barrier function in a weaned piglet model of Escherichia coli infection

2011 ◽  
Vol 106 (6) ◽  
pp. 870-877 ◽  
Author(s):  
Julia B. Ewaschuk ◽  
Gordon K. Murdoch ◽  
Ian R. Johnson ◽  
Karen L. Madsen ◽  
Catherine J. Field
Keyword(s):  
Escherichia Coli ◽  
Protein Expression ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Tissue ◽  
E Coli ◽  
Tight Junction Protein Expression ◽  
Junction Protein

The weaning period is associated with an increased prevalence of gastrointestinal infection in many species. Glutamine (Gln) has been shown to improve intestinal barrier function and immune function in both in vivo and in vitro models. The objective of the present study was to determine the effect of dietary Gln supplementation on intestinal barrier function and intestinal cytokines in a model of Escherichia coli infection. We randomised 21-d-old piglets (n 20) to nutritionally complete isonitrogenous diets with or without Gln (4·4 %, w/w) for 2 weeks. Intestinal loops were isolated from anaesthetised pigs and inoculated with either saline or one of the two E. coli (K88AC or K88 wild-type)-containing solutions. Intestinal tissue was studied for permeability, cytokine expression, fluid secretion and tight-junction protein expression. Animals receiving Gln supplementation had decreased potential difference (PD) and short-circuit current (Isc) in E. coli-inoculated intestinal loops (PD 0·628 (sem 0·151) mV; Isc 13·0 (sem 3·07) μA/cm2) compared with control-fed animals (PD 1·36 (sem 0·227) mV; Isc 22·4 (sem 2·24) μA/cm2). Intestinal tissue from control, but not from Gln-supplemented, animals responded to E. coli with a significant increase in mucosal cytokine mRNA (IL-1β, IL-6, transforming growth factor-β and IL-10). Tight-junction protein expression (claudin-1 and occludin) was reduced with exposure to E. coli in control-fed animals and was not influenced in Gln-supplemented piglets. Gln supplementation may be useful in reducing the severity of weaning-related gastrointestinal infections, by reducing the mucosal cytokine response and altering intestinal barrier function.

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