scholarly journals Algal Oil Rich in n-3 PUFA Alleviates DSS-Induced Colitis via Regulation of Gut Microbiota and Restoration of Intestinal Barrier

2020 ◽  
Vol 11 ◽  
Author(s):  
Zhenxia Xu ◽  
Hu Tang ◽  
Fenghong Huang ◽  
Zhixian Qiao ◽  
Xu Wang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Intestinal Microbiota ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Neutrophil Infiltration ◽  
Tight Junction Proteins ◽  
Mice Model ◽  
Colonic Inflammation ◽  
Algal Oil ◽  
Junction Proteins

Algal oil is rich in docosahexaenoic acid (DHA) and has various health benefits against human metabolic disorders and disease. This study aimed to investigate the effects of DHA algal oil on colonic inflammation and intestinal microbiota in dextran sulfate sodium (DSS)-induced colitis mice model. Male C57BL/6 mice was induced colitis by 2.5% DSS and followed by 2 weeks of treatment with algal oil (250 or 500 mg/kg/day). The colonic inflammation was assessed by colon macroscopic damage scores, and the degree of neutrophil infiltration was evaluated by measuring tissue-associated myeloperoxidase (MPO) activity in colonic mucosa. Tight junction proteins in the colonic tissue were measured by real-time PCR and western blot. Moreover, the intestinal microbiota and shot chain fatty acids (SCFAs) were estimated by bioinformatic analysis and GC, respectively. Colonic damage due to DSS treatment was significantly ameliorated by algal oil supplementation. In addition, algal oil significantly inhibited the increases of malondialdehyde (MDA) content, MPO activity, pro-inflammatory cytokines level and tight junction proteins expression in DSS-treated mice. Furthermore, supplementation of algal oil modulated the intestinal microbiota structure in DSS induced colitis mice by increasing the proportion of the unidentified_S24_7 and decreasing the relative abundance of unidentified_Ruminococcaceae, Clostridium and Roseburia. On the analysis of SCFAs, the caecal content of acetic acid, propionic acid, isobutyric acid, buturic, and the total SCFAs showed a significant increase in algal oil-administered mice. Together, these results suggested that algal oil rich in DHA inhibited the progress of DSS-induced colitis in mice by modulating the intestinal microbiota and metabolites and repairing the intestinal barrier, which may be applied in the development of therapeutics for intestinal inflammation.

Protection of Intestinal Barrier in Uremic Mice by Electroacupuncture via Regulating the Cannabinoid 1 Receptor of the Intestinal Glial Cells

2021 ◽  
Vol 17 (11) ◽  
pp. 2210-2218
Author(s):  
Feng Li ◽  
Guangjian Zhang ◽  
Jing Liang ◽  
Yu Ma ◽  
Jian Huang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Glial Cells ◽  
Cannabinoid Receptor ◽  
Intestinal Barrier ◽  
Mice Model ◽  
Jnk Pathway ◽  
Cannabinoid 1 Receptor ◽  
Junction Protein ◽  
Receptor Signaling Pathway ◽  
Junction Proteins

Intestinal barrier injuries are common in uremia, which aggravates uremia. The goal of this study is to learn moreabout how electroacupuncture regulates gastrointestinal function, as well as to identify the importance of microglia in electroacupuncture regulation and the cannabinoid receptor signaling pathway in controlling the activity of intestinal glial cells. The mice were arbitrarily assigned to four groups: control, CKD, electroacupuncture stimulation, or AM251 (CB1 receptor antagonist). The mice model of uremia was established by adenine gavage. Western blotting revealed the development of tight junction proteins ZO-1, cannabinoid 1 receptor, glial specific GFAP, occludin, S100 β, claudin-1, and JNK. GFAP and CB1R protein expression and co-localization of the intestinal glial cells were observed by double-labeled fluorescence. The expression of cannabinoid 1 receptor CB1R in the intestinal glial cells was increased after electroacupuncture. The expression of tight junction protein, GFAP, S100 β, and CB1R protein was up-regulated after electroacupuncture, and the dysfunction of the intestinal barrier in uremia was corrected. Nevertheless, AM251, a CB1R antagonist, reversed the effect of electroacupuncture. Electroacupuncture can protect the intestinal barrier through the intestinal glial cell CB1R, and the effect is achieved by inhibiting the JNK pathway.

scholarly journals The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction

2010 ◽  
Vol 298 (5) ◽  
pp. G625-G633 ◽  
Author(s):  
Wei Zhong ◽  
Craig J. McClain ◽  
Matthew Cave ◽  
Y. James Kang ◽  
Zhanxiang Zhou
Keyword(s):  
Oxidative Stress ◽  
Tight Junction ◽  
Zinc Deficiency ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Alcohol Exposure ◽  
Epithelial Barrier ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Junction Proteins

Disruption of the intestinal barrier is a causal factor in the development of alcoholic endotoxemia and hepatitis. This study was undertaken to determine whether zinc deficiency is related to the deleterious effects of alcohol on the intestinal barrier. Mice were pair fed an alcohol or isocaloric liquid diet for 4 wk, and hepatitis was detected in association with elevated blood endotoxin level. Alcohol exposure significantly increased the permeability of the ileum but did not affect the barrier function of the duodenum or jejunum. Reduction of tight-junction proteins at the ileal epithelium was detected in alcohol-fed mice although alcohol exposure did not cause apparent histopathological changes. Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species. Caco-2 cell culture demonstrated that alcohol exposure increases the intracellular free zinc because of oxidative stress. Zinc deprivation caused epithelial barrier disruption in association with disassembling of tight junction proteins in the Caco-2 monolayer cells. Furthermore, minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. In conclusion, epithelial barrier dysfunction in the distal small intestine plays an important role in alcohol-induced gut leakiness, and zinc deficiency attributable to oxidative stress may interfere with the intestinal barrier function by a direct action on tight junction proteins or by sensitizing to the effects of alcohol.

Adalimumab prevents barrier dysfunction and antagonizes distinct effects of TNF-α on tight junction proteins and signaling pathways in intestinal epithelial cells

2013 ◽  
Vol 304 (11) ◽  
pp. G970-G979 ◽  
Author(s):  
Andreas Fischer ◽  
Markus Gluth ◽  
Ulrich-Frank Pape ◽  
Bertram Wiedenmann ◽  
Franz Theuring ◽  
...  
Keyword(s):  
Tight Junction ◽  
Inflammatory Bowel Diseases ◽  
Intestinal Barrier ◽  
Model Systems ◽  
Tight Junction Proteins ◽  
Barrier Dysfunction ◽  
Tnf Α ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Junction Proteins

Intestinal barrier dysfunction is pivotal in the etiology of inflammatory bowel diseases. Combined clinical and endoscopic remission (“mucosal healing”) in patients who received anti-TNF-α therapies suggests restitution of the intestinal barrier, but the mechanisms involved are largely unknown. We therefore investigated the impact of the anti-TNF-α antibody adalimumab on barrier function in two in vitro models. Combined stimulation of Caco-2 and T-84 cells with interferon-γ and TNF-α resulted in a significant decrease of transepithelial electrical resistance (TEER) within 6 h that was prevented by adalimumab in concentrations down to 100 ng/ml. Adalimumab furthermore antagonized the appearance of irregular membrane undulations and prevented internalization of tight junction proteins upon cytokine exposure. In addition, TNF-α induced a downregulation of claudin-1, claudin-2, claudin-4, and occludin as well as activation of phosphatidylinositol 3-kinase signaling in T-84 but not Caco-2 cells, which was reversed by adalimumab. At the signaling level, adalimumab prevented increased phosphorylation of myosin light chain as well as activation of p38 MAPK and NF-κB accompanying the decline in TEER in both model systems. Pharmacological inhibition of NF-κB signaling partially prevented the TNF-α-induced TEER loss, whereas inhibition of p38 worsened barrier dysfunction in Caco-2 but not T-84 cells. Taken together, these data demonstrate that adalimumab prevents barrier dysfunction induced by TNF-α both functionally and structurally as well as at the level of signal transduction. Barrier protection might therefore constitute a novel mechanism how anti-TNF-α therapy contributes to epithelial restitution and tissue repair in inflammatory bowel diseases.

scholarly journals The Role of β-Carotene in Colonic Inflammation and Intestinal Barrier Integrity

2021 ◽  
Vol 8 ◽  
Author(s):  
Junrui Cheng ◽  
Emilio Balbuena ◽  
Baxter Miller ◽  
Abdulkerim Eroglu
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Signaling Pathway ◽  
Tight Junction Proteins ◽  
Colonic Epithelial Cells ◽  
Colonic Inflammation ◽  
Tlr4 Signaling Pathway ◽  
Β Carotene ◽  
Junction Proteins

Background: Carotenoids are naturally occurring pigments accounting for the brilliant colors of fruits and vegetables. They may display antioxidant and anti-inflammatory properties in humans besides being precursors to vitamin A. There is a gap of knowledge in examining their role within colonic epithelial cells. We proposed to address this research gap by examining the effects of a major dietary carotenoid, β-carotene, in the in vitro epithelial cell model.Methods: We examined the function of β-carotene in the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway. We conducted western blotting assays to evaluate expressions of TLR4 and its co-receptor, CD14. We also examined NF-κB p65 subunit protein levels in the model system. Furthermore, we studied the impact of β-carotene on the tight junction proteins, claudin-1, and occludin. We further carried out immunocytochemistry experiments to detect and visualize claudin-1 expression.Results: β-Carotene reduced LPS-induced intestinal inflammation in colonic epithelial cells. β-Carotene also promoted the levels of tight junction proteins, which might lead to enhanced barrier function.Conclusions: β-Carotene could play a role in modulating the LPS-induced TLR4 signaling pathway and in enhancing tight junction proteins. The findings will shed light on the role of β-carotene in colonic inflammation and also potentially in metabolic disorders since higher levels of LPS might induce features of metabolic diseases.

scholarly journals Effects of multi-strain probiotic supplementation on intestinal microbiota, tight junctions, and inflammation in young broiler chickens challenged with Salmonella enterica subsp. enterica

2020 ◽  
Vol 33 (11) ◽  
pp. 1797-1808
Author(s):  
Chi Huan Chang ◽  
Po Yun Teng ◽  
Tzu Tai Lee ◽  
Bi Yu
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Intestinal Microbiota ◽  
Broiler Chickens ◽  
Infected Group ◽  
Tight Junction Proteins ◽  
Probiotic Supplementation ◽  
Mucin 2 ◽  
Ifn Γ ◽  
Junction Proteins

Objective: This study assessed the effects of probiotics on cecal microbiota, gene expression of intestinal tight junction proteins, and immune response in the cecal tonsil of broiler chickens challenged with Salmonella enterica subsp. enterica.Methods: One-day-old broiler chickens (n = 240) were randomly allocated to four treatments: negative control (Cont), multi-strain probiotic-treated group (Pro), Salmonella-infected group (Sal), and multi-strain probiotic-treated and Salmonella-infected group (ProSal). All chickens except those in the Cont and Pro groups were gavaged with 1×10<sup>8</sup> cfu/mL of S. enterica subsp. enterica 4 days after hatching.Results: Our results indicated that body weight, weight gain, and feed conversion ratio of birds were significantly reduced (p<0.05) by Salmonella challenge. Chickens challenged with Salmonella decreased cecal microbial diversity. Chickens in the Sal group exhibited abundant Proteobacteria than those in the Cont, Pro, and ProSal groups. Salmonella infection downregulated gene expression of Occludin, zonula occludens-1 (ZO1), and Mucin 2 in the jejunum and Occludin and Claudin in the ileum. Moreover, the Sal group increased gene expression of interferon-γ (IFN-γ), interleukin-6 (IL-6), IL-1β, and lipopolysaccharide-induced tumor necrosis factor-alpha factor (LITAF) and reduced levels of transforming growth factor-β4 and IL-10 compared with the other groups (p<0.05). However, chickens receiving probiotic diets increased Lactobacillaceae abundance and reduced Enterobacteriaceae abundance in the ceca. Moreover, supplementation with probiotics increased the mRNA expression of Occludin, ZO1, and Mucin 2 in the ileum (p<0.05). In addition, probiotic supplementation downregulated the mRNA levels of IFN-γ (p<0.05) and LITAF (p = 0.075) and upregulated IL-10 (p = 0.084) expression in the cecal tonsil.Conclusion: The administration of multi-strain probiotics modulated intestinal microbiota, gene expression of tight junction proteins, and immunomodulatory activity in broiler chickens.

Red wine extract preserves tight junctions in intestinal epithelial cells under inflammatory conditions: implications for intestinal inflammation

2019 ◽  
Vol 10 (3) ◽  
pp. 1364-1374 ◽  
Author(s):  
Carla Nunes ◽  
Víctor Freitas ◽  
Leonor Almeida ◽  
João Laranjinha
Keyword(s):  
Red Wine ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Epithelial ◽  
Tight Junction Proteins ◽  
Inflammatory Conditions ◽  
Inflammatory Stimuli ◽  
Wine Polyphenols ◽  
Red Wine Polyphenols ◽  
Junction Proteins

Red wine polyphenols protect the intestinal barrier against inflammatory stimuli by modulating the gene expression of key tight junction proteins.

MO445BRAIN AND GUT AXIS IN CHRONIC KIDNEY DISEASE: FOCUS ON SPECIFIC BIOMARKERS, AND TIGHT JUNCTION PROTEINS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Leah Hernandez ◽  
Liam Ward ◽  
Thomas Ebert ◽  
Samsul Arefin ◽  
Olof Heimbürger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tight Junction ◽  
Kidney Transplant ◽  
Subcutaneous Fat ◽  
Intestinal Barrier ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Tight Junction Proteins ◽  
Junction Proteins

Abstract Background and Aims Chronic kidney disease (CKD) is a progressive systemic disease that affect the microvascular permeability of the blood-brain barrier (BBB) and intestinal barrier leading to increased morbidity, mortality and central nervous system symptoms. In this study we examined the relationship of blood brain and intestinal barrier dysfunction in relation to uraemic environment and increased risk of developing neurologic complications and mortality. In addition, potential proteins conferring the junctional communications were assessed. Method The study included serum samples from 216 prevalent haemodialysis (HD), 80 peritoneal dialysis (PD) and 80 healthy subjects. Permeability of the BBB was evaluated by measuring serum concentrations for brain-specific biomarkers S100B, NSE (neuron specific enolase), BDNF (brain-derived neurotrophic factor), GFAP (glial fibrillary acidic protein) using ELISA. TMAO (trimethylamine-N-Oxide) as a surrogate of gut generated uraemic toxins was analysed by mass spectrophotometry. Subcutaneous fat tissues with identified microvessels from 10 kidney transplant recipients and 11 donors were examined for expression of tight junction proteins claudin-5, occludin and JAM-1 (junction adhesion molecule-1) by immunohistochemical staining. Results HD and PD groups showed elevated cholesterol, triglyceride, creatinine, hsCRP and lower BMI, and P-albumin compared to healthy controls. BDNF serum concentrations were lower in both HD (14.0 ng/mL, IQR 8.7-19.2) and PD (17.9 ng/mL, IQR 14.4-23.4) vs controls (20.2 ng/mL, IQR 16.7-25.7). Similarly, S100B serum concentrations were lower in both HD (31.6 pg/mL, IQR 9.4-186) and PD (49.4 pg/mL, IQR 9.8-118) vs control (87.3 pg/mL, IQR 13.3-749). Conversely, NSE serum concentrations were higher in both HD (5.3 ng/mL, IQR 4.4-6.6) and PD (4.0 ng/mL, IQR 3.6-4.7) vs controls (3.5 ng/mL, IQR 2.9-4.3). Finally, TMAO serum concentration were also higher in both HD (6.4 ng/μL, IQR 4.0-11.2) and PD (3.8 ng/μL, IQR 2.2-6.3) vs controls (0.4 ng/μL, IQR 0.3-0.6). No significant sex differences in biomarker concentration were found, except for TMAO in healthy controls. Immunohistochemistry studies of endothelial tight junction proteins in microvessels, within the subcutaneous fat tissues, showed reduced expression of claudin-5 (5%), occludin (6%) and JAM-1 (5%) in kidney transplant patients vs donors (7%, 8% and 8%, respectively), and ongoing studies are indicating a trend for altered expression of tight junction proteins after ex vivo stimulation with TMAO. Conclusion We report that CKD5 patients showed disruption of BBB and intestinal barrier resulting in altered circulating serum levels of brain-specific biomarkers, secondary to a disruption in the tight junction protein markers in microvasculature of adipose tissue. These findings imply that it is important to continuously monitor cognitive function(s) in CKD. Further studies are needed to assess direct effect of TMAO on tight junction proteins which confer vascular permeability.

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