scholarly journals Intestinal Barrier Function in Gluten-Related Disorders

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2325 ◽  
Author(s):  
Danielle Cardoso-Silva ◽  
Deborah Delbue ◽  
Alice Itzlinger ◽  
Renée Moerkens ◽  
Sebo Withoff ◽  
...  

Gluten-related disorders include distinct disease entities, namely celiac disease, wheat-associated allergy and non-celiac gluten/wheat sensitivity. Despite having in common the contact of the gastrointestinal mucosa with components of wheat and other cereals as a causative factor, these clinical entities have distinct pathophysiological pathways. In celiac disease, a T-cell mediate immune reaction triggered by gluten ingestion is central in the pathogenesis of the enteropathy, while wheat allergy develops as a rapid immunoglobulin E- or non-immunoglobulin E-mediated immune response. In non-celiac wheat sensitivity, classical adaptive immune responses are not involved. Instead, recent research has revealed that an innate immune response to a yet-to-be-defined antigen, as well as the gut microbiota, are pivotal in the development in this disorder. Although impairment of the epithelial barrier has been described in all three clinical conditions, its role as a potential pathogenetic co-factor, specifically in celiac disease and non-celiac wheat sensitivity, is still a matter of investigation. This article gives a short overview of the mucosal barrier of the small intestine, summarizes the aspects of barrier dysfunction observed in all three gluten-related disorders and reviews literature data in favor of a primary involvement of the epithelial barrier in the development of celiac disease and non-celiac wheat sensitivity.

1993 ◽  
Vol 264 (1) ◽  
pp. G143-G149 ◽  
Author(s):  
P. Kubes

The objective of this study was to assess whether nitric oxide synthesis inhibition affects intestinal barrier function after ischemia-reperfusion of the feline small bowel. Local intra-arterial infusion of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol.ml-1.min-1) was performed in autoperfused segments of cat ileum for 60 min after 90 min of ischemia and 60 min of reperfusion. Epithelial permeability was quantitated by measuring blood-to-lumen clearance of 51Cr-labeled EDTA, and microvascular dysfunction was assessed by measuring the clearance of protein from the vasculature into the interstitium. 125I-labeled albumin clearance from blood to lumen and histology were performed to further characterize the extent of intestinal dysfunction after reperfusion of the postischemic intestine in the presence and absence of L-NAME. Ischemia-reperfusion-induced mucosal and microvascular permeability increases were dramatically augmented by L-NAME infusion, and this effect was reversed by infusion of L-arginine (125 nmol.ml-1.min-1). Initiating L-arginine (but not D-arginine) infusion alone 10 min before reperfusion provided protection against ischemia-reperfusion-induced mucosal barrier dysfunction; however, this was not associated with a reduction in endogenous levels of L-arginine during ischemia-reperfusion. These data suggest that basal nitric oxide production is important in minimizing mucosal and microvascular barrier dysfunction associated with reperfusion of postischemic intestine.


2018 ◽  
Vol 1 ◽  
Author(s):  
Murphy L.Y. Wan ◽  
Ka Ho Ling ◽  
Hani El-Nezami ◽  
Mingfu Wang

Deoxynivalenol (DON) is a major mycotoxin contaminant and is known to impair intestinal barrier function. Previous experiments in our laboratory have proven that polyphenols such as resveratrol (RES) may be effective in enhancing epithelial barrier function. Due to the structural similarity of oxyresveratrol (OXY) with RES, it was hypothesized that OXY could also protect against DON-induced intestinal damage. Accordingly, this study aimed to explore potential protective effects of OXY against DON-induced epithelial barrier dysfunction and bacterial translocation on IPEC-J2 cells, in comparison to resveratrol (RES).The results showed that OXY increased transepithelial electrical resistance (TEER) and reduced FD-4 diffusion, whereas DON reduced TEER and increased FD-4 diffusion in IPEC-J2 cells. On the other hand, OXY reduced FD-4 diffusion in DON-damaged cells but showed no significant difference in terms of TEER. Such protective effects coincided with the significantly reduced E. coli translocation in cells co-exposed to DON and OXY. Further mechanistic studies demonstrated that OXY protected against DON-induced barrier dysfunction by enhancing the expression of claudin-4 via mitogen-activated protein kinase(MAPK)-dependent pathways. Apparently, OXY worked through the same way as RES did, with results dovetailed nicely with anticipation. These results imply that OXY may share similar health benefits with RES by enhancing epithelial barrier functions and protecting against DON-induced intestinal damage.


2017 ◽  
Vol 8 (3) ◽  
pp. 1144-1151 ◽  
Author(s):  
Qianru Chen ◽  
Oliver Chen ◽  
Isabela M. Martins ◽  
Hu Hou ◽  
Xue Zhao ◽  
...  

Alaska pollock skin derived collagen peptides could be considered as dietary supplements for intestinal barrier function promotion and associated diseases.


2001 ◽  
Vol 280 (1) ◽  
pp. G7-G13 ◽  
Author(s):  
Johan D. Söderholm ◽  
Mary H. Perdue

The influence of stress on the clinical course of a number of intestinal diseases is increasingly being recognized, but the underlying mechanisms are largely unknown. This themes article focuses on recent findings related to the effects of stress on mucosal barrier function in the small intestine and colon. Experiments using animal models demonstrate that various types of psychological and physical stress induce dysfunction of the intestinal barrier, resulting in enhanced uptake of potentially noxious material (e.g., antigens, toxins, and other proinflammatory molecules) from the gut lumen. Evidence from several studies indicates that in this process, mucosal mast cells play an important role, possibly activated via neurons releasing corticotropin-releasing hormone and/or acetylcholine. Defining the role of specific cells and mediator molecules in stress-induced barrier dysfunction may provide clues to novel treatments for intestinal disorders.


2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  

B cell-activating factor (BAFF) production is increased in septic patients. However, the specific role of BAFF in sepsis remains unknown. This study was designed to investigate the expression and function of BAFF in an experimental endotoxemia model and to identify the potential mechanisms. We established an endotoxemia mouse (6–8 weeks, 20–22 g) model by administering 30 mg/kg lipopolysaccharide (LPS). BAFF levels in the circulating system and organ tissues were measured 4 and 8 h after LPS injection. Survival rates in the endotoxemia mice were monitored for 72 h after BAFF blockade. The effects of BAFF blockade on systemic and local inflammation, organ injuries, and intestinal barrier function were also evaluated 4 h after LPS treatment. BAFF production was systemically and locally elevated after LPS challenge. BAFF blockade improved the survival rate, systemic inflammation, and multi-organ injuries. Moreover, BAFF blockade attenuated both intestinal inflammation and impaired intestinal permeability. BAFF blockade upregulated ZO-1 and occludin protein levels via the NF-κB/MLCK/MLC signaling pathway. These results suggested that BAFF blockade protects against lethal endotoxemia at least partially by alleviating inflammation, multi-organ injuries, and improving intestinal barrier function and provides a novel focus for further research on sepsis and experimental evidence for clinical therapy.


Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 527
Author(s):  
Jie Fu ◽  
Tenghao Wang ◽  
Xiao Xiao ◽  
Yuanzhi Cheng ◽  
Fengqin Wang ◽  
...  

This study investigated the effects of dietary C. butyricum ZJU-F1 on the apparent digestibility of nutrients, intestinal barrier function, immune response, and microflora of weaned piglets, with the aim of providing a theoretical basis for the application of Clostridium butyricum as an alternative to antibiotics in weaned piglets. A total of 120 weanling piglets were randomly divided into four treatment groups, in which piglets were fed a basal diet supplemented with antibiotics (CON), Bacillus licheniformis (BL), Clostridium butyricum ZJU-F1 (CB), or Clostridium butyricum and Bacillus licheniformis (CB-BL), respectively. The results showed that CB and CB-BL treatment increased the intestinal digestibility of nutrients, decreased intestinal permeability, and increased intestinal tight junction protein and mucin expression, thus maintaining the integrity of the intestinal epithelial barrier. CB and CB-BL, as exogenous probiotics, were also found to stimulate the immune response of weaned piglets and improve the expression of antimicrobial peptides in the ileum. In addition, dietary CB and CB-BL increased the proportion of Lactobacillus. The levels of butyric acid, propionic acid, acetic acid, and total acid were significantly increased in the ceca of piglets fed CB and CB-BL. Furthermore, we validated the effects of C. butyricum ZJU-F1 on the intestinal barrier function and immune response in vitro and found C. butyricum ZJU-F1 improved intestinal function and enhanced the TLR-2-MyD88-NF-κB signaling.


Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  

The intestinal epithelium provides a barrier against commensal and pathogenic microorganisms. Barrier dysfunction promotes chronic inflammation, which can drive the pathogenesis of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although the Signal Transducer and Activator of Transcription-3 (STAT3) is overexpressed in both intestinal epithelial cells and immune cells in IBD patients, the role of the interleukin (IL)-6 family of cytokines through the shared IL-6ST/gp130 receptor and its associated STAT3 signalling in intestinal barrier integrity is unclear. We therefore investigated the role of STAT3 in retaining epithelial barrier integrity using dextran sulfate sodium (DSS)-induced colitis in two genetically modified mouse models, to either reduce STAT1/3 activation in response to IL-6 family cytokines with a truncated gp130∆STAT allele (GP130∆STAT/+), or by inducing short hairpin-mediated knockdown of Stat3 (shStat3). Here, we show that mice with reduced STAT3 activity are highly susceptible to DSS-induced colitis. Mechanistically, the IL-6/gp130/STAT3 signalling cascade orchestrates intestinal barrier function by modulating cytokine secretion and promoting epithelial integrity to maintain a defence against bacteria. Our study also identifies a crucial role of STAT3 in controlling intestinal permeability through tight junction proteins. Thus, therapeutically targeting the IL-6/gp130/STAT3 signalling axis to promote barrier function may serve as a treatment strategy for IBD patients.


Biomedicines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 67 ◽  
Author(s):  
Shara Francesca Rapa ◽  
Rosanna Di Paola ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
...  

Intestinal epithelial barrier impairment plays a key pathogenic role in inflammatory bowel diseases (IBDs). In particular, together with oxidative stress, intestinal epithelial barrier alteration is considered as upstream event in ulcerative colitis (UC). In order to identify new products of natural origin with a potential activity for UC treatment, this study evaluated the effects of plumericin, a spirolactone iridoid, present as one of the main bioactive components in the bark of Himatanthus sucuuba (Woodson). Plumericin was evaluated for its ability to improve barrier function and to reduce apoptotic parameters during inflammation, both in intestinal epithelial cells (IEC-6), and in an animal experimental model of 2, 4, 6-dinitrobenzene sulfonic acid (DNBS)-induced colitis. Our results indicated that plumericin increased the expression of adhesion molecules, enhanced IEC-6 cells actin cytoskeleton rearrangement, and promoted their motility. Moreover, plumericin reduced apoptotic parameters in IEC-6. These results were confirmed in vivo. Plumericin reduced the activity of myeloperoxidase, inhibited the expression of ICAM-1, P-selectin, and the formation of PAR, and reduced apoptosis parameters in mice colitis induced by DNBS. These results support a pharmacological potential of plumericin in the treatment of UC, due to its ability to improve the structural integrity of the intestinal epithelium and its barrier function.


2021 ◽  
Author(s):  
Benthe van der Lugt ◽  
Maartje C.P. Vos ◽  
Mechteld Grootte Bromhaar ◽  
Noortje Ijssennagger ◽  
Frank Vrieling ◽  
...  

2019 ◽  
Vol 5 ◽  
pp. 18-30 ◽  
Author(s):  
Jonathan C. Valdez ◽  
Bradley W. Bolling

Chronic intestinal inflammation, occurring in inflammatory bowel diseases (IBD), is associated with compromised intestinal barrier function. Inflammatory cytokines disrupt tight junctions and increase paracellular permeability of luminal antigens. Thus, chronic intestinal barrier dysfunction hinders the resolution of inflammation. Dietary approaches may help mitigate intestinal barrier dysfunction and chronic inflammation. A growing body of work in rodent models of colitis has demonstrated that berry consumption inhibits chronic intestinal inflammation. Berries are a rich dietary source of polyphenolic compounds, particularly anthocyanins. However, berry anthocyanins have limited bioavailability and are extensively metabolized by the gut microbiota and host tissue. This review summarizes the literature regarding the beneficial functions of anthocyanin-rich berries in treating and preventing IBD. Here, we will establish the role of barrier function in the pathogenesis of IBD and how dietary anthocyanins and their known microbial catabolites modulate intestinal barrier function.


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