scholarly journals Probiotics Prevents Sensitization to Oral Antigen and Subsequent Increases in Intestinal Tight Junction Permeability in Juvenile–Young Adult Rats

2019 ◽  
Vol 7 (10) ◽  
pp. 463 ◽  
Author(s):  
Tulyeu ◽  
Kumagai ◽  
Jimbo ◽  
Watanabe ◽  
Yokoyama ◽  
...  
Keyword(s):  
Food Allergy ◽  
Young Adult ◽  
Gut Microbiota ◽  
Tight Junction ◽  
Intestinal Permeability ◽  
Lactobacillus Reuteri ◽  
Intestinal Barrier ◽  
Mucosal Inflammation ◽  
Adult Rats ◽  
Epithelial Barrier Function

Increased intestinal permeability is thought to underlie the pathogenesis of food allergy. We explore the mechanism responsible for changes in the morphology and function of the intestinal barrier using a rat model of food allergy, focusing on the contribution of intestinal microbiota. Juvenile–young adult rats were sensitized with ovalbumin and treated with antibiotics or probiotics (Clostridium butyricum and Lactobacillus reuteri), respectively. The serum ovalbumin-IgE levels, intestinal permeability, histopathological features, tight junction (TJ)-associated proteins, Th2 cytokines, and gut microbiota in feces were analyzed in each group. Sensitized rats showed an increase in ovalbumin-IgE levels and intestinal permeability with gut mucosal inflammation, whereas rats that received probiotics were only mildly affected. Rats given ovalbumin, but not those given probiotics, showed a reduction in both TJ-related protein expression and localization. Th2 cytokine levels were increased in the sensitized rats, but not in those given probiotics. TJs in rats treated with ovalbumin and antibiotics were disrupted, but those in rats administered probiotics were undamaged. Clostridiaceae were increased in the probiotics groups, especially Alkaliphilus, relative to the ovalbumin-sensitized group. Gut microbiota appears to play a role in regulating epithelial barrier function, and probiotics may help to prevent food sensitization through the up-regulation of TJ proteins.

scholarly journals Antibiotic-Induced Gut Microbiota Dysbiosis Damages the Intestinal Barrier, Increasing Food Allergy in Adult Mice

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3315
Author(s):  
Qiuyu Zhang ◽  
Lei Cheng ◽  
Junjuan Wang ◽  
Mengzhen Hao ◽  
Huilian Che
Keyword(s):  
Food Allergy ◽  
Inflammatory Response ◽  
Gut Microbiota ◽  
Tight Junction ◽  
Intestinal Barrier ◽  
Later Life ◽  
Food Allergies ◽  
Tight Junction Proteins ◽  
Gut Microbiota Dysbiosis ◽  
Junction Proteins

(1) Background: The use of antibiotics affects the composition of gut microbiota. Studies have suggested that the colonization of gut microbiota in early life is related to later food allergies. Still, the relationship between altered intestinal microbiota in adulthood and food allergies is unclear. (2) Methods: We established three mouse models to analyze gut microbiota dysbiosis’ impact on the intestinal barrier and determine whether this effect can increase the susceptibility to and severity of food allergy in later life. (3) Results: The antibiotic-induced gut microbiota dysbiosis significantly reduced Lachnospiraceae, Muribaculaceae, and Ruminococcaceae, and increased Enterococcaceae and Clostridiales. At the same time, the metabolic abundance was changed, including decreased short-chain fatty acids and tryptophan, as well as enhanced purine. This change is related to food allergies. After gut microbiota dysbiosis, we sensitized the mice. The content of specific IgE and IgG1 in mice serum was significantly increased, and the inflammatory response was enhanced. The dysbiosis of gut microbiota caused the sensitized mice to have more severe allergic symptoms, ruptured intestinal villi, and a decrease in tight junction proteins (TJs) when re-exposed to the allergen. (4) Conclusions: Antibiotic-induced gut microbiota dysbiosis increases the susceptibility and severity of food allergies. This event may be due to the increased intestinal permeability caused by decreased intestinal tight junction proteins and the increased inflammatory response.

scholarly journals A Polysaccharide Isolated from Dictyophora indusiata Promotes Recovery from Antibiotic-Driven Intestinal Dysbiosis and Improves Gut Epithelial Barrier Function in a Mouse Model

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 1003 ◽  
Author(s):  
Sadia Kanwal ◽  
Thomson Patrick Joseph ◽  
Lawrence Owusu ◽  
Ren Xiaomeng ◽  
Li Meiqi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Tight Junction ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Illumina Miseq ◽  
Intestinal Barrier Function ◽  
Protective Effects ◽  
Necrosis Factor Alpha ◽  
Epithelial Barrier Function ◽  
Associated Proteins

Despite the tremendous biological activity of polysaccharides from the mushroom Dictyophora indusiata, its role in the restoration of gut microbiota has not yet been explored. The present study aimed to investigate whether D. indusiata polysaccharide (DIP) could modulate the recovery of gut microbiota composition and intestinal barrier function after broad-spectrum antibiotic-driven dysbiosis. Alteration and restoration in the microbial communities were elucidated by the Illumina MiSeq platform. Colon histology, expression of tight-junction associated proteins, and serum/tissue endotoxin and cytokine levels were evaluated. Two-week daily oral administration of clindamycin and metronidazole resulted in reduced bacterial diversity and richness, and perturbed the microbial flora at various taxonomic levels (altered Firmicutes/Bacteroidetes ratio and increased relative abundance of harmful flora (Proteobacteria, Enterococcus, and Bacteroides)), whereas DIP administration reversed the dysbiosis and increased beneficial flora, including Lactobacillaceae (lactic acid-producing bacteria), and Ruminococaceae (butyrate-producing bacteria). In addition, it resulted in the reduction of endotoxemia (through lipopolysaccharides (LPSs)) and pro-inflammatory cytokine (tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β)) levels, with the increased expression of tight-junction associated proteins (claudin-1, occludin, and zonula occludens-1). These findings not only suggested a comprehensive understanding of the protective effects of a DIP in the restoration of gut microbiota but also highlighted its role in the enhancement of gut barrier integrity, reduction of inflammation and lowering of endotoxin levels in mice.

scholarly journals Tight joints and zonulin in the formation of oral tolerance and food allergy

2019 ◽  
pp. 5-9
Author(s):  
N. G. Prikhodchenko ◽  
T. A. Shumatova ◽  
L. A. Grigoryan ◽  
A. V. Gordeets
Keyword(s):  
Food Allergy ◽  
Intestinal Permeability ◽  
Oral Tolerance ◽  
Intestinal Barrier ◽  
Molecular Entity ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Pathological Conditions ◽  
Diagnostic Criterion

Summary: The study represents a review of publications covering molecular entity of intestinal permeability and changes causing its disorders. The current concepts on intestinal barrier, tight joints (TJ) and intestinal permeability under normal and pathological conditions are covered. Special attention has been given to molecular unions of tight joints; a role of dysregulation of the components of the TJ complex in the formation of oral tolerance and food allergy is disclosed. It is shown that the assessment of the intestinal epithelial barrier condition can be a significant diagnostic criterion to control the disease and to assess the effectiveness of treatment.

scholarly journals Qingchang Wenzhong Decoction Accelerates Intestinal Mucosal Healing Through Modulation of Dysregulated Gut Microbiome, Intestinal Barrier and Immune Responses in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhongmei Sun ◽  
Junxiang Li ◽  
Wenting Wang ◽  
Yuyue Liu ◽  
Jia Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Mucosal Healing ◽  
Intestinal Stem Cells ◽  
Mucosal Inflammation ◽  
Protective Effects ◽  
Fecal Microbiome ◽  
Epithelial Regeneration

Inflammatory bowel disease (IBD), a group of multifactorial and inflammatory infirmities, is closely associated with dysregulation of gut microbiota and host metabolome, but effective treatments are currently limited. Qingchang Wenzhong Decoction (QCWZD) is an effective and classical traditional herbal prescription for the treatment of IBD and has been proved to attenuate intestinal inflammation in a model of acute colitis. However, the role of QCWZD in recovery phase of colitis is unclear. Here, we demonstrated that mice treated with QCWZD showed a faster recovery from dextran sulfate sodium (DSS)-induced epithelial injury, accompanied by reduced mucosal inflammation and attenuated intestinal dysbiosis using bacterial 16S rRNA amplicon sequencing compared to those receiving sterile water. The protective effects of QCWZD are gut microbiota dependent, as demonstrated by fecal microbiome transplantation and antibiotics treatment. Gut microbes transferred from QCWZD-treated mice displayed a similar role in mucosal protection and epithelial regeneration as QCWZD on colitis in mice, and depletion of the gut microbiota through antibiotics treatments diminished the beneficial effects of QCWZD on colitis mice. Moreover, metabolomic analysis revealed metabolic profiles alternations in response to the gut microbiota reprogrammed by QCWZD intervention, especially enhanced tryptophan metabolism, which may further accelerate intestinal stem cells-mediated epithelial regeneration to protect the integrity of intestinal mucosa through activation of Wnt/β-catenin signals. Collectively, our results suggested that orally administrated QCWZD accelerates intestinal mucosal healing through the modulation of dysregulated gut microbiota and metabolism, thus regulating intestinal stem cells-mediated epithelial proliferation, and hold promise for novel microbial-based therapies in the treatment of IBD.

scholarly journals Wheat gluten intake increases the severity of experimental colitis and bacterial translocation by weakening of the proteins of the junctional complex

2018 ◽  
Vol 121 (4) ◽  
pp. 361-373 ◽  
Author(s):  
Penélope L. R. Menta ◽  
Maria E. R. Andrade ◽  
Paola C. L. Leocádio ◽  
Júlia R. Fraga ◽  
Melissa T. S. Dias ◽  
...  
Keyword(s):  
Intestinal Permeability ◽  
Bacterial Translocation ◽  
Wheat Gluten ◽  
Intestinal Barrier ◽  
Mucosal Inflammation ◽  
Intestinal Barrier Function ◽  
Junctional Complex ◽  
Standard Diet ◽  
Colonic Injury ◽  
Adhesion Junctions

AbstractGluten is only partially digested by intestinal enzymes and can generate peptides that can alter intestinal permeability, facilitating bacterial translocation, thus affecting the immune system. Few studies addressed the role of diet with gluten in the development of colitis. Therefore, we investigate the effects of wheat gluten-containing diet on the evolution of sodium dextran sulphate (DSS)-induced colitis. Mice were fed a standard diet without (colitis group) or with 4·5 % wheat gluten (colitis + gluten) for 15 d and received DSS solution (1·5 %, w/v) instead of water during the last 7 d. Compared with the colitis group, colitis + gluten mice presented a worse clinical score, a larger extension of colonic injury area, and increased mucosal inflammation. Both intestinal permeability and bacterial translocation were increased, propitiating bacteria migration for peripheral organs. The mechanism by which diet with gluten exacerbates colitis appears to be related to changes in protein production and organisation in adhesion junctions and desmosomes. The protein α-E-catenin was especially reduced in mice fed gluten, which compromised the localisation of E-cadherin and β-catenin proteins, weakening the structure of desmosomes. The epithelial damage caused by gluten included shortening of microvilli, a high number of digestive vacuoles, and changes in the endosome/lysosome system. In conclusion, our results show that wheat gluten-containing diet exacerbates the mucosal damage caused by colitis, reducing intestinal barrier function and increasing bacterial translocation. These effects are related to the induction of weakness and disorganisation of adhesion junctions and desmosomes as well as shortening of microvilli and modification of the endocytic vesicle route.

Vasoactive intestinal peptide ameliorates intestinal barrier disruption associated withCitrobacter rodentium-induced colitis

2009 ◽  
Vol 297 (4) ◽  
pp. G735-G750 ◽  
Author(s):  
V. S. Conlin ◽  
X. Wu ◽  
C. Nguyen ◽  
C. Dai ◽  
B. A. Vallance ◽  
...  
Keyword(s):  
Tight Junction ◽  
Myosin Light Chain ◽  
Intestinal Barrier ◽  
Paracellular Permeability ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Epithelial Barrier Function ◽  
Junction Proteins

Attaching and effacing bacterial pathogens attach to the apical surface of epithelial cells and disrupt epithelial barrier function, increasing permeability and allowing luminal contents access to the underlying milieu. Previous in vitro studies demonstrated that the neuropeptide vasoactive intestinal peptide (VIP) regulates epithelial paracellular permeability, and the high concentrations and close proximity of VIP-containing nerve fibers to intestinal epithelial cells would support such a function in vivo. The aim of this study was to examine whether VIP treatment modulated Citrobacter rodentium-induced disruption of intestinal barrier integrity and to identify potential mechanisms of action. Administration of VIP had no effect on bacterial attachment although histopathological scoring demonstrated a VIP-induced amelioration of colitis-induced epithelial damage compared with controls. VIP treatment prevented the infection-induced increase in mannitol flux a measure of paracellular permeability, resulting in levels similar to control mice, and immunohistochemical studies demonstrated that VIP prevented the translocation of tight junction proteins: zonula occludens-1, occludin, and claudin-3. Enteropathogenic Escherichia coli (EPEC) infection of Caco-2 monolayers confirmed a protective role for VIP on epithelial barrier function. VIP prevented EPEC-induced increase in long myosin light chain kinase (MLCK) expression and myosin light chain phosphorylation (p-MLC). Furthermore, MLCK inhibition significantly attenuated bacterial-induced epithelial damage both in vivo and in vitro. In conclusion, our results indicate that VIP protects the colonic epithelial barrier by minimizing bacterial-induced redistribution of tight junction proteins in part through actions on MLCK and MLC phosphorylation.

scholarly journals Dexmedetomidine protects against burn-induced intestinal barrier injury via the MLCK/p-MLC signalling pathway

2020 ◽  
Author(s):  
Chao Qin ◽  
Yi Jiang ◽  
Xing Chen ◽  
Yingxue Bian ◽  
Yaoqi Wang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Intestinal Permeability ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Burn Injury ◽  
Intestinal Barrier ◽  
Signalling Pathway ◽  
Tight Junction Proteins ◽  
Anti Inflammatory ◽  
Junction Proteins

Abstract Background Dexmedetomidine, a potent α2-adrenoceptor agonist with analgesic, sedative, anti-inflammatory, and anti-apoptotic effects, is commonly used in patients with critical illness in intensive care units. Accumulating evidence indicates that dexmedetomidine can protect against intestinal dysfunction. However, the specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. Here, we aimed to explore the possible positive effects of dexmedetomidine on burn-induced intestinal barrier injury and the role of the myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signalling pathway in an experimental model of burn injury.Methods In this study, the intestinal permeability of burn-induced intestinal barrier damage was assessed by estimating the plasma concentration of 4.4 kDa fluorescein isothiocyanate-labelled dextran (FITC-dextran). Histological changes were evaluated using haematoxylin and eosin (HE) staining. Tight junction proteins were evaluated by western blot and immunofluorescence analyses to assess the structural integrity of intestinal tight junctions. The level of inflammation was determined by enzyme-linked immunosorbent assay (ELISA).Results Our findings demonstrated that the increase in intestinal permeability caused by burn injury is accompanied by histological damage to the intestine, decreases in the expression of the tight junction proteins Zonula Occludens-1 (ZO-1) and Occludin, increases in inflammatory cytokine levels and elevation of both MLCK protein expression and MLC phosphorylation. After dexmedetomidine treatment, the burn-induced changes were ameliorated.Conclusions In conclusion, dexmedetomidine exerted an anti‑inflammatory effect and protected tight junction complexes against burn‑induced intestinal barrier damage by inhibiting the MLCK/p-MLC signalling pathways, suggesting that it may be an effective drug in the treatment of burn-induced intestinal injury.Trial registration Not appliance.

scholarly journals Increased intestinal permeability and gut dysbiosis in the R6/2 mouse model of Huntington’s disease

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tiberiu Loredan Stan ◽  
Rana Soylu-Kucharz ◽  
Stephen Burleigh ◽  
Olena Prykhodko ◽  
Ling Cao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tight Junction ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Intestinal Permeability ◽  
Intestinal Barrier ◽  
Systemic Circulation ◽  
Intestinal Lumen ◽  
Protein Levels ◽  
Junction Proteins

Abstract Huntington’s disease (HD) is a progressive, multifaceted neurodegenerative disease associated with weight loss and gut problems. Under healthy conditions, tight junction (TJ) proteins maintain the intestinal barrier integrity preventing bacterial translocation from the intestinal lumen to the systemic circulation. Reduction of TJs expression in Parkinson’s disease patients has been linked with increased intestinal permeability—leaky gut syndrome. The intestine contains microbiota, most dominant phyla being Bacteroidetes and Firmicutes; in pathogenic or disease conditions the balance between these bacteria might be disrupted. The present study investigated whether there is evidence for an increased intestinal permeability and dysbiosis in the R6/2 mouse model of HD. Our data demonstrate that decreased body weight and body length in R6/2 mice is accompanied by a significant decrease in colon length and increased gut permeability compared to wild type littermates, without any significant changes in the protein levels of the tight junction proteins (occludin, zonula occludens). Moreover, we found an altered gut microbiota in R6/2 mice with increased relative abundance of Bacteroidetes and decreased of Firmicutes. Our results indicate an increased intestinal permeability and dysbiosis in R6/2 mice and further studies investigating the clinical relevance of these findings are warranted.

scholarly journals Lactobacillus reuteri LR1 Improved Expression of Genes of Tight Junction Proteins via the MLCK Pathway in IPEC-1 Cells during Infection with Enterotoxigenic Escherichia coli K88

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Hongbo Yi ◽  
Li Wang ◽  
Yunxia Xiong ◽  
Zhilin Wang ◽  
Yueqin Qiu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Tight Junction ◽  
Lactobacillus Reuteri ◽  
Transcript Abundance ◽  
Enterotoxigenic Escherichia Coli ◽  
Epithelial Barrier ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Intestinal Epithelial Barrier ◽  
Epithelial Barrier Function

Intestinal epithelial barrier damage disrupts immune homeostasis and leads to many intestinal disorders. Lactobacillus reuteri strains have probiotic functions in their modulation of the microbiota and immune system in intestines. In this study, the effects of L. reuteri LR1, a new strain isolated from the feces of weaning piglets, on intestinal epithelial barrier damage in IPEC-1 cells caused by challenge with enterotoxigenic Escherichia coli (ETEC) K88 were examined. It was found that L. reuteri LR1, in large part, offset the ETEC K88-induced increase in permeability of IPEC-1 cell monolayers and decreased the adhesion and invasion of the coliform in IPEC-1 cells. In addition, L. reuteri LR1 increased transcript abundance and protein contents of tight junction (TJ) proteins zonula occluden-1 (ZO-1) and occludin in ETEC K88-infected IPEC-1 cells, whereas it had no effects on claudin-1 and F-actin expression. Using colloidal gold immunoelectron microscopy, these effects of L. reuteri LR1 on ZO-1 and occludin content in IPEC-1 cells were confirmed. By using ML-7, a selective inhibitor of myosin light-chain kinase (MLCK), the beneficial effect of L. reuteri LR1 on contents of ZO-1 and occludin was shown to be dependent on the MLCK pathway. In conclusion, L. reuteri LR1 had beneficial effects on epithelial barrier function consistent with increasing ZO-1 and occludin expression via a MLCK-dependent manner in IPEC-1 cells during challenge with ETEC K88.

scholarly journals Alleviation Effects of GQD, a Traditional Chinese Medicine Formula, on Diabetes Rats Linked to Modulation of the Gut Microbiome

2021 ◽  
Vol 11 ◽  
Author(s):  
Jiaxing Tian ◽  
Bingbing Bai ◽  
Zezheng Gao ◽  
Yingying Yang ◽  
Haoran Wu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Gut Microbiota ◽  
Protective Effect ◽  
Intestinal Permeability ◽  
Barrier Function ◽  
Pathogenic Bacteria ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Rrna Gene ◽  
Islet Function

Gegen Qinlian Decoction (GQD) is a Chinese herbal medicine that has been reported to significantly decrease blood glucose levels, which is suggested to be related to interactions with the gut microbiota. However, the protective effect of GQD on intestinal barrier function with regard to its influence on the gut microbiota has not been explored to date. In this study, we investigated the role of the gut microbiota in mediating the hypoglycemic mechanism of GQD in type 2 diabetes mellitus (T2DM) rats induced by a single intraperitoneal injection of streptozotocin after 4 weeks of high-fat diet feeding. The T2DM rats were randomly allocated to receive GQD, metformin (Met), or saline for 12 consecutive weeks, and changes in metabolic parameters, intestinal barrier function, and inflammation were investigated. Gut microbiota was analyzed using 16S rRNA gene sequencing from fecal samples, and statistical analyses were performed to correlate microbiota composition with phenotypes of the T2DM rats. GQD administration decreased the levels of blood glucose and inflammatory cytokines, and increased the levels of tight junction proteins. Besides, GQD had a protective effect on islet function, restoring intestinal permeability, and inhibiting inflammation, as evidenced by increases in the levels of serum C-peptide, occludin, and claudin-1 in the colon, and also improved the expression of serum inflammatory factors. In addition, GQD regulated the structure of the gut microbiota by increasing the proportions of short-chain fatty acids-producing and anti-inflammatory bacteria, and decreasing the proportions of conditioned pathogenic bacteria associated with the diabetic phenotype. Overall, these findings suggest that GQD could ameliorate hyperglycemia and protect islet function by regulating the structure of the gut microbiota, thereby restoring intestinal permeability and inhibiting inflammation in T2DM rats. Our study thus suggests that the hypoglycemic mechanism of GQD is mediated by its modulation of the gut microbiota.

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