Bioactive factors secreted by Bifidobacterium breve B-3 enhance barrier function in human intestinal Caco-2 cells

2019 ◽  
Vol 10 (1) ◽  
pp. 89-100 ◽  
Author(s):  
Y. Kurose ◽  
J. Minami ◽  
A. Sen ◽  
N. Iwabuchi ◽  
F. Abe ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Barrier Function ◽  
Promoter Activity ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Barrier Integrity ◽  
Bifidobacterium Breve ◽  
Enhancing Effect

Intestinal barrier function is closely related to intestinal health and diseases. Recent studies demonstrate that some probiotic and commensal bacteria secrete metabolites that are capable of affecting the intestinal functions. The present study examined an enhancing effect of bioactive factors secreted by Bifidobacterium breve strain B-3 on the intestinal tight junction (TJ) barrier integrity in human intestinal Caco-2 cells. Administration of conditioned medium obtained from B. breve strain B-3 (B3CM) to Caco-2 cells for 24 h increased trans-epithelial electrical resistance (TER), a TJ barrier indicator, across their monolayers. Immunoblot, immunofluorescence, and qPCR analyses demonstrated that B3CM increased an integral TJ protein, claudin-4 expression. In luciferase reporter assay, the administration of B3CM enhanced the claudin-4 promoter activity, indicating the transcriptional upregulation of claudin-4. Site-directed mutation of specificity protein 1 (Sp1) binding sites in the claudin-4 promoter sequence and suppression of Sp1 expression by siRNA technology clearly reduced the enhancing effect of B3CM on claudin-4 promoter activity. Liquid chromatography/mass spectrometry detected a significant amount of acetic acid in B3CM (28.3 mM). The administration of acetic acid to Caco-2 cells partially mimicked a B3CM-mediated increase in TER, but failed to increase claudin-4 expression. Taken together, bioactive factors secreted by B. breve B-3 enhanced the TJ barrier integrity in intestinal Caco-2 cells. Transcriptional regulation of claudin-4 through Sp1 is at least in part one of the underlying molecular mechanisms. In addition, acetic acid contributes to the B3CM-mediated barrier effect independently of claudin-4 expression.

Influence of Plant Bioactive Compounds on Intestinal Epithelial Barrier in Poultry

2020 ◽  
Vol 20 (7) ◽  
pp. 566-577 ◽  
Author(s):  
Amlan Kumar Patra
Keyword(s):  
Bioactive Compounds ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Digestive Enzyme ◽  
Intestinal Barrier ◽  
Feed Additives ◽  
Interactive Effects ◽  
Intestinal Barrier Function ◽  
Poultry Production ◽  
Poultry Feeding

Natural plant bioactive compounds (PBC) have recently been explored as feed additives to improve productivity, health and welfare of poultry following ban or restriction of in-feed antibiotic use. Depending upon the types of PBC, they possess antimicrobial, digestive enzyme secretion stimulation, antioxidant and many pharmacological properties, which are responsible for beneficial effects in poultry production. Moreover, they may also improve the intestinal barrier function and nutrient transport. In this review, the effects of different PBC on the barrier function, permeability of intestinal epithelia and their mechanism of actions are discussed, focusing on poultry feeding. Dietary PBC may regulate intestinal barrier function through several molecular mechanisms by interacting with different metabolic cascades and cellular transcription signals, which may then modulate expressions of genes and their proteins in the tight junction (e.g., claudins, occludin and junctional adhesion molecules), adherens junction (e.g., E-cadherin), other intercellular junctional proteins (e.g., zonula occludens and catenins), and regulatory proteins (e.g., kinases). Interactive effects of PBC on immunomodulation via expressions of several cytokines, chemokines, complement components, pattern recognition receptors and their transcription factors and cellular immune system, and alteration of mucin gene expressions and goblet cell abundances in the intestine may change barrier functions. The effects of PBC are not consistent among the studies depending upon the type and dose of PBC, physiological conditions and parts of the intestine in chickens. An effective concentration in diets and specific molecular mechanisms of PBC need to be elucidated to understand intestinal barrier functionality in a better way in poultry feeding.

scholarly journals STAT3 Signalling via the IL-6ST/gp130 Cytokine Receptor Promotes Epithelial Integrity and Intestinal Barrier Function during DSS-Induced Colitis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 187
Author(s):  
Lokman Pang ◽  
Jennifer Huynh ◽  
Mariah G. Alorro ◽  
Xia Li ◽  
Matthias Ernst ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Epithelial Integrity ◽  
Barrier Integrity ◽  
Gp130 Receptor ◽  
Stat3 Signalling

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.

scholarly journals Macrophage Deficiency Makes Intestinal Epithelial Cells Susceptible to NSAID-Induced Damage

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xinxin Wang ◽  
Jiayang Wang ◽  
Tianyu Xie ◽  
Shuo Li ◽  
Di Wu ◽  
...  
Keyword(s):  
T Cells ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Epithelial Proliferation ◽  
Gm Csf ◽  
Mucosal Barrier Function

Objectives. In Crohn’s disease (CD), the mechanisms underlying the regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of mucosal barrier function in the ileum are unclear. We analyzed the molecular mechanisms underlying the regulation by GM-CSF of the mucosal barrier function. Methods. We examined the role of GM-CSF in the intestinal barrier function in CD at the molecular-, cellular-, and animal-model levels. Results. Macrophages directly secreted GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis, which maintained intestinal barrier function. Macrophages were absent in NSAID-induced ileitis, causing GM-CSF deficiency, increasing the apoptosis rate, decreasing the proliferation rate, increasing inter- and paracellular permeabilities, decreasing the TJP levels, and reducing the numbers of mesenteric lymph nodes, memory T cells, and regulatory T cells in Csf1op/op transgenic mice. Conclusions. GM-CSF is required for the maintenance of intestinal barrier function. Macrophages directly secrete GM-CSF, promoting intestinal epithelial proliferation and inhibiting apoptosis.

scholarly journals Health-Promoting Properties of Proanthocyanidins for Intestinal Dysfunction

Nutrients ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 130 ◽  
Author(s):  
Carlos González-Quilen ◽  
Esther Rodríguez-Gallego ◽  
Raúl Beltrán-Debón ◽  
Montserrat Pinent ◽  
Anna Ardévol ◽  
...  
Keyword(s):  
Barrier Function ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Experimental Models ◽  
Intestinal Barrier Function ◽  
Grape Seeds ◽  
Inflammatory Conditions ◽  
Bacterial Endotoxins ◽  
Health Promoting

The intestinal barrier is constantly exposed to potentially harmful environmental factors, including food components and bacterial endotoxins. When intestinal barrier function and immune homeostasis are compromised (intestinal dysfunction), inflammatory conditions may develop and impact overall health. Evidence from experimental animal and cell culture studies suggests that exposure of intestinal mucosa to proanthocyanidin (PAC)-rich plant products, such as grape seeds, may contribute to maintaining the barrier function and to ameliorating the pathological inflammation present in diet-induced obesity and inflammatory bowel disease. In this review, we aim to update the current knowledge on the bioactivity of PACs in experimental models of intestinal dysfunction and in humans, and to provide insights into the underlying biochemical and molecular mechanisms.

scholarly journals 2’-fucosyllactose (2’-FL) Supplementation Improves Gut Barrier Function and Lipid Metabolism in HF-fed Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 425-425
Author(s):  
Sunhye Lee ◽  
Michael Goodson ◽  
Wendie Vang ◽  
Karen Kalanetra ◽  
Daniela Barile ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Gut Barrier ◽  
Low Fat ◽  
Barrier Integrity ◽  
Gut Barrier Function

Abstract Objectives 2’-fucosyllactose (2’-FL), the most predominant oligosaccharide found in human milk, acts as a prebiotic with beneficial effects on the host. The aim of this study was to determine the beneficial effect of 2’-FL on intestinal barrier integrity and metabolic functions in low-fat (LF)- and high-fat (HF)-fed mice. Methods Male C57/BL6 mice (n = 32, 8/group; 6 weeks old, JAX, CA) were counter-balanced into four weight-matched groups and fed either a low-fat (LF; 10% kcal fat with 7% kcal sucrose) or HF (45% kcal fat with 17% kcal sucrose) with or without supplementation of 2’-FL in the diet [10% (w/w), 8 weeks; LF/2’-FL or HF/2’-FL; BASF, Germany]. General phenotypes (body weight, energy intake, fat and lean mass), intestinal permeability (ex vivo in Ussing chambers), lipid profiles, and microbial metabolites were assessed. Results 2’-FL significantly attenuated the HF-induced increase in body fat mass with a trend to decrease body weight gain. 2’-FL significantly decreased intestinal permeability in LF-fed mice with a trend for a decrease in HF-fed mice. This was associated with a significant increase in interleukin-22, a cytokine known to have a protective role in intestinal barrier function. Visceral adipocyte size was significantly decreased by 2’-FL in both LF- and HF-fed mice. 2’-FL suppressed HF-induced upregulation of adipogenic transcription factors peroxisome proliferator-activated receptor gamma and sterol regulatory element binding protein-1c in the liver. Lastly, 2’-FL supplementation led to a significant elevation of lactic acid concentration in the cecum of HF-fed mice, which is known to be a product from beneficial microbes. Conclusions 2’-FL supplementation improved gut barrier integrity and lipid metabolism in mice with and without the metabolic challenge of HF feeding. These findings support the use of 2’-FL in the control of gut barrier function and metabolic homeostasis under normal and abnormal physiological conditions. Funding Sources BASF (Germany).

scholarly journals Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis

2020 ◽  
Author(s):  
Elliot Yi-Hsin Lin ◽  
Hsuan-Ju Lai ◽  
Yuan-Kai Cheng ◽  
Kai-Quan Leong ◽  
Li-Chieh Cheng ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Experimental Colitis ◽  
Neutrophil Extracellular Trap ◽  
Mucosal Barrier ◽  
Mucosal Inflammation ◽  
Intestinal Barrier Function ◽  
Trinitrobenzene Sulfonic Acid ◽  
Barrier Integrity

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

scholarly journals MiR-126 impairs the intestinal barrier function via inhibiting S1PR2 mediated activation of PI3K/AKT signaling pathway

2017 ◽  
Author(s):  
Tanzhou Chen ◽  
Haibo Xue ◽  
Ruoyang Lin ◽  
Zhiming Huang
Keyword(s):  
Signaling Pathway ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Akt Signaling ◽  
Mucosal Barrier ◽  
Intestinal Barrier Function ◽  
Luciferase Reporter ◽  
Akt Signaling Pathway ◽  
Intestinal Mucosal Barrier ◽  
Pathological Tissues

AbstractBackgroundAberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD.MethodsIn this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2. The transendothelial electrical resistance assay was used to measured the value of TEER.ResultsThe expressions of miR-126, S1PR2 and S1P in the pathological tissues of IBD patients were significantly higher than that of the control group. Moreover, miR-126 overexpression contributed to intestinal mucosal barrier dysfunction in vitro. S1PR2 was a direct target of miR-126, and S1PR2 expression was negatively regulated by miR-126 in Caco-2 cells. However, S1PR2 activated by S1P had the protection effect for the integrity and permeability of intestinal mucosal barrier via a PI3K/Akt dependent mechanism. MiR-126 silencing possessed obvious protective effects on the intestinal barrier function, but these effects could be reversed by JTE-013 or LY294002.ConclusionMiR-126 down-regulated S1PR2 and then prevented the activation of PI3K/AKT signaling pathway, which ultimately could damage intestinal mucosal barrier function.

scholarly journals Neutrophil Extracellular Traps Impair Intestinal Barrier Function during Experimental Colitis

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 275
Author(s):  
Elliot Yi-Hsin Lin ◽  
Hsuan-Ju Lai ◽  
Yuan-Kai Cheng ◽  
Kai-Quan Leong ◽  
Li-Chieh Cheng ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Experimental Colitis ◽  
Neutrophil Extracellular Trap ◽  
Mucosal Barrier ◽  
Mucosal Inflammation ◽  
Intestinal Barrier Function ◽  
Trinitrobenzene Sulfonic Acid ◽  
Barrier Integrity

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

scholarly journals Role of microRNAs in Disorders of Gut–Brain Interactions: Clinical Insights and Therapeutic Alternatives

2021 ◽  
Vol 11 (10) ◽  
pp. 1021
Author(s):  
Rajan Singh ◽  
Hannah Zogg ◽  
Seungil Ro
Keyword(s):  
Barrier Function ◽  
Molecular Mechanisms ◽  
Intestinal Barrier ◽  
Cell Types ◽  
Enteric Neurons ◽  
Intestinal Barrier Function ◽  
Pathophysiological Mechanisms ◽  
Mrna Targets ◽  
Therapeutic Alternatives ◽  
Brain Interactions

Disorders of gut–brain interactions (DGBIs) are heterogeneous in nature and intertwine with diverse pathophysiological mechanisms. Regular functioning of the gut requires complex coordinated interplay between a variety of gastrointestinal (GI) cell types and their functions are regulated by multiple mechanisms at the transcriptional, post-transcriptional, translational, and post-translational levels. MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate gene expression by binding to specific mRNA targets to repress their translation and/or promote the target mRNA degradation. Dysregulation of miRNAs might impair gut physiological functions leading to DGBIs and gut motility disorders. Studies have shown miRNAs regulate gut functions such as visceral sensation, gut immune response, GI barrier function, enteric neuronal development, and GI motility. These biological processes are highly relevant to the gut where neuroimmune interactions are key contributors in controlling gut homeostasis and functional defects lead to DGBIs. Although extensive research has explored the pathophysiology of DGBIs, further research is warranted to bolster the molecular mechanisms behind these disorders. The therapeutic targeting of miRNAs represents an attractive approach for the treatment of DGBIs because they offer new insights into disease mechanisms and have great potential to be used in the clinic as diagnostic markers and therapeutic targets. Here, we review recent advances regarding the regulation of miRNAs in GI pacemaking cells, immune cells, and enteric neurons modulating pathophysiological mechanisms of DGBIs. This review aims to assess the impacts of miRNAs on the pathophysiological mechanisms of DGBIs, including GI dysmotility, impaired intestinal barrier function, gut immune dysfunction, and visceral hypersensitivity. We also summarize the therapeutic alternatives for gut microbial dysbiosis in DGBIs, highlighting the clinical insights and areas for further exploration. We further discuss the challenges in miRNA therapeutics and promising emerging approaches.

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