scholarly journals Yogurt inhibits intestinal barrier dysfunction in Caco-2 cells by increasing tight junctions

2017 ◽  
Vol 8 (1) ◽  
pp. 406-414 ◽  
Author(s):  
Kelley K. Putt ◽  
Ruisong Pei ◽  
Heather M. White ◽  
Bradley W. Bolling
Keyword(s):  
Tight Junctions ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction

Yogurt improves inflammation-disrupted intestinal barrier function in differentiated Caco-2 cells.

scholarly journals OP0245 MICROBIOTA-INDUCED INTESTINAL BARRIER DYSFUNCTION PRECEDES THE ONSET OF ARTHRITIS AND ALLOWS THE SHUTTLING OF IMMUNE CELLS FROM THE GUT THE JOINTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 154.2-154
Author(s):  
M. Zaiss ◽  
N. Taijc ◽  
K. Sarter ◽  
V. Azizov ◽  
L. Bucci ◽  
...  
Keyword(s):  
Tight Junction ◽  
Tight Junctions ◽  
Immune Cells ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Microbial Dysbiosis ◽  
Intestinal Dysbiosis

Background:While it is known that microbial dysbiosis is associated with the onset of rheumatoid arthritis, mechanistic insights how it facilitates the development of arthritis remained largely elusive to date. It is especially interesting how microbial dysbiosis affects the transition from asymptomatic autoimmunity to arthritis. We speculated that a breakdown of intestinal barrier function caused by microbial dysbiosis allows immune cells to shuttle from the gut to the joints.Objectives:To test whether intestinal barrier function is impaired before the onset of human RA and experimental arthritis and to seek for evidence that immune cells from the gut migrate to the joints.Methods:In a longitudinal cohort of RA-at risk individuals markers of disturbed intestinal barrier function, such as zonulin, were analysed and linked to RA onset. Furthermore, new-onset RA patients were assessed for gut leakiness and their intestinal biopsies for the expression of tight junction proteins and immune cell infiltration. In the murine model of collagen-induced arthritis, sequential analysis of intestinal dysbiosis, intestinal barrier function and arthritis onset was carried out. Additionally, barrier function was assessed on intestinal organoids exposed to faecal supernatants from eu- and dysbiotic mice with and without inhibition of zonulin. Furthermore, three types of interventions restoring intestinal barrier function were carried out for testing their effects on the inhibition of arthritis onset. Finally, photo- converted cells from the gut were traced in the joints to test for cellular trafficking from one to the other compartment.Results:Zonulin, a potent regulator for intestinal tight junctions, was elevated in autoimmune mice and men before the onset of arthritis and predicted the onset of human RA. Intestinal barrier functions as well as epithelial tight junctions were decreased before the onset of experimental arthritis and at onset of human RA. In mice, induction of autoimmunity was followed by rapid intestinal dysbiosis followed by gut leakiness before arthritis started. Faecal supernatants of arthritic mice induce epithelial barrier dysfunction in intestinal organoids in zonulin dependent manner. Restoration of the intestinal barrier in the pre-phase of arthritis using butyrate, CB1R agonist or zonulin antagonist larazotide inhibited the development of arthritis. Finally, using photoconvertible mice, gut-borne immune cells were identified that homed to the joints when barrier function was impaired.Conclusion:In summary, these data show the intestinal barrier dysfunction precedes the onset of RA and allows the trafficking of immune cells from the gut to the joints. Targeting of intestinal tight junction function may therefore allow preventing the onset of RA.Acknowledgments:Funded by the DFG-FOR2886 PANDORA, DFG–CRC118, Staedtler foundation, Johannes und Frieda Marohn-Stiftung, Else Kröner-Fresenius foundation, Interdisciplinary Centre for Clinical Research, Erlangen (IZKF), BMBF-MASCARA and the IMI funded projectRTCure.Disclosure of Interests:Mario Zaiss: None declared, Narges Taijc: None declared, Kerstin Sarter: None declared, Vugar Azizov: None declared, laura Bucci: None declared, Yubin Luo: None declared, Juan de Dios Cañete: None declared, francesco ciccia Grant/research support from: pfizer, novartis, roche, Consultant of: pfizer, novartis, lilly, abbvie, Speakers bureau: pfizer, novartis, lilly, abbvie, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB

scholarly journals Anthocyanins and intestinal barrier function: a review

2019 ◽  
Vol 5 ◽  
pp. 18-30 ◽  
Author(s):  
Jonathan C. Valdez ◽  
Bradley W. Bolling
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Berry Anthocyanins ◽  
Chronic Intestinal Inflammation

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.

scholarly journals Curcumin improves intestinal barrier function: modulation of intracellular signaling, and organization of tight junctions

2017 ◽  
Vol 312 (4) ◽  
pp. C438-C445 ◽  
Author(s):  
Jing Wang ◽  
Siddhartha S. Ghosh ◽  
Shobha Ghosh
Keyword(s):  
Type 2 Diabetes ◽  
Tight Junctions ◽  
Barrier Function ◽  
Intracellular Signaling ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Oral Supplementation

Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as type 2 diabetes and atherosclerosis) has shifted the focus from high-fat high-cholesterol containing Western-type diet (WD)-induced changes in gut microbiota per se to release of gut bacteria-derived products (e.g., LPS) into circulation due to intestinal barrier dysfunction as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. We demonstrated earlier that oral supplementation with curcumin attenuates WD-induced development of type 2 diabetes and atherosclerosis. Poor bioavailability of curcumin has precluded the establishment of a causal relationship between oral supplementation and it is in vivo effects. We hypothesized that curcumin attenuates WD-induced chronic inflammation and associated metabolic diseases by modulating the function of intestinal epithelial cells (IECs) and the intestinal barrier function. The objective of the present study was to delineate the underlying mechanisms. The human IEC lines Caco-2 and HT-29 were used for these studies and modulation of direct as well as indirect effects of LPS on intracellular signaling as well as tight junctions were examined. Pretreatment with curcumin significantly attenuated LPS-induced secretion of master cytokine IL-1β from IECs and macrophages. Furthermore, curcumin also reduced IL-1β-induced activation of p38 MAPK in IECs and subsequent increase in expression of myosin light chain kinase involved in the phosphorylation of tight junction proteins and ensuing disruption of their normal arrangement. The major site of action of curcumin is, therefore, likely the IECs and the intestinal barrier, and by reducing intestinal barrier dysfunction, curcumin modulates chronic inflammatory diseases despite poor bioavailability.

scholarly journals Protective Effects of Let-7b on the Expression of Occludin by Targeting P38 MAPK in Preventing Intestinal Barrier Dysfunction

2018 ◽  
Vol 45 (1) ◽  
pp. 343-355 ◽  
Author(s):  
Zhihua Liu ◽  
Yinghai Tian ◽  
Yanqiong Jiang ◽  
Shihua Chen ◽  
Ting Liu ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Conditional Knockout ◽  
Intestinal Barrier Function ◽  
Control Group ◽  
Protective Effects ◽  
Barrier Dysfunction ◽  
Entire Study ◽  
Intestinal Barrier Dysfunction

Background/Aims: Let-7b was dramatically reduced after a dicer knockout of mice with intestinal barrier function injuries. This paper aims to investigate the molecular mechanism of let-7b by targeting p38 MAPK in preventing intestinal barrier dysfunction. Methods: A total of 186 patients were enrolled, with 93 in the control group and 93 in the PRO group. Only 158 patients completed the entire study, whereas the others either did not meet the inclusion criteria or refused to participate. To further verify the role of let-7b, intestinal epithelial conditional knockout (IKO) mice of mmu-let-7b model were established. Serum let-7b, zonulin, IL-6, and TNF-α concentrations were measured by ELISA or quantitative RT-PCR. Permeability assay was done by ussing chamber. The apoptotic cells were identified using an In Situ Cell Death Detection Kit. Protein was detected by western blot. Results: Probiotics can lower infection-related complications, as well as increase the serum and tissue let-7b levels. P38 MAPK was identified as the target of let-7b, as verified by NCM460 cells. P38 MAPK expression was increased, whereas tight-junction (TJ) proteins were significantly decreased in let-7b IKO mice (both P<0.05). Negative regulation of p38 MAPK molecular signaling pathways was involved in the protective effects of let-7b on intestinal barrier function. Conclusion: Let-7b was identified as a novel diagnosis biomarker or a potential treatment target for preventing intestinal barrier dysfunction.

scholarly journals Mesenchymal stem cell-derived microvesicles improve intestinal barrier function by restoring mitochondrial dynamic balance in sepsis rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Danyang Zheng ◽  
Henan Zhou ◽  
Hongchen Wang ◽  
Yu Zhu ◽  
Yue Wu ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Intestinal Epithelial Cells ◽  
Dynamic Balance ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Barrier Dysfunction ◽  
Mitochondrial Dynamic ◽  
Intestinal Barrier Dysfunction

Abstract Background Sepsis is a major cause of death in ICU, and intestinal barrier dysfunction is its important complication, while the treatment is limited. Recently, mesenchymal stem cell-derived microvesicles (MMVs) attract much attention as a strategy of cell-free treatment; whether MMVs are therapeutic in sepsis induced-intestinal barrier dysfunction is obscure. Methods In this study, cecal ligation and puncture-induced sepsis rats and lipopolysaccharide-stimulated intestinal epithelial cells to investigate the effect of MMVs on intestinal barrier dysfunction. MMVs were harvested from mesenchymal stem cells and were injected into sepsis rats, and the intestinal barrier function was measured. Afterward, MMVs were incubated with intestinal epithelial cells, and the effect of MMVs on mitochondrial dynamic balance was measured. Then the expression of mfn1, mfn2, OPA1, and PGC-1α in MMVs were measured by western blot. By upregulation and downregulation of mfn2 and PGC-1α, the role of MMVs in mitochondrial dynamic balance was investigated. Finally, the role of MMV-carried mitochondria in mitochondrial dynamic balance was investigated. Results MMVs restored the intestinal barrier function by improving mitochondrial dynamic balance and metabolism of mitochondria. Further study revealed that MMVs delivered mfn2 and PGC-1α to intestinal epithelial cells, and promoted mitochondrial fusion and biogenesis, thereby improving mitochondrial dynamic balance. Furthermore, MMVs delivered functional mitochondria to intestinal epithelial cells and enhanced energy metabolism directly. Conclusion MMVs can deliver mfn2, PGC-1α, and functional mitochondria to intestinal epithelial cells, synergistically improve mitochondrial dynamic balance of target cells after sepsis, and restore the mitochondrial function and intestinal barrier function. The study illustrated that MMVs might be a promising strategy for the treatment of sepsis.

scholarly journals BAFF Blockade Attenuates Inflammatory Responses and Intestinal Barrier Dysfunction in a Murine Endotoxemia Model

2020 ◽  
Vol 11 ◽  
Author(s):  
Runze Quan ◽  
Chaoyue Chen ◽  
Wei Yan ◽  
Ying Zhang ◽  
Xi Zhao ◽  
...  
Keyword(s):  
Barrier Function ◽  
Intestinal Inflammation ◽  
Inflammatory Responses ◽  
Survival Rates ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Barrier Dysfunction ◽  
Protein Levels ◽  
Lps Challenge ◽  
Endotoxemia Model

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.

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 Trifostigmanoside I, an Active Compound from Sweet Potato, Restores the Activity of MUC2 and Protects the Tight Junctions through PKCα/β to Maintain Intestinal Barrier Function

2020 ◽  
Vol 22 (1) ◽  
pp. 291
Author(s):  
Amna Parveen ◽  
Seungho Choi ◽  
Ju-Hee Kang ◽  
Seung Hyun Oh ◽  
Sun Yeou Kim
Keyword(s):  
Tight Junctions ◽  
Sweet Potato ◽  
Barrier Function ◽  
Intestinal Barrier ◽  
Human Colon ◽  
Underlying Mechanism ◽  
Intestinal Barrier Function ◽  
Isolation And Identification ◽  
Human Colon Cancer ◽  
Mucin Production

Sweet potato (Ipomoea batata) is considered a superfood among vegetables and has been consumed for centuries. Traditionally, sweet potato is used to treat several illnesses, including diarrhea and stomach disorders. This study aimed to explore the protective effect of sweet potato on intestinal barrier function, and to identify the active compounds of sweet potato and their underlying mechanism of action. To this purpose, bioactivity-guided isolation, Western blotting, and immunostaining assays were applied. Interestingly, our bioactivity-guided approach enabled the first isolation and identification of trifostigmanoside I (TS I) from sweet potato. TS I induced mucin production and promoted the phosphorylation of PKCα/β in LS174T human colon cancer cells. In addition, it protected the function of tight junctions in the Caco-2 cell line. These findings suggest that TS I rescued the impaired abilities of MUC2, and protected the tight junctions through PKCα/β, to maintain intestinal barrier function.

scholarly journals Bifidobacteria Stabilize Claudins at Tight Junctions and Prevent Intestinal Barrier Dysfunction in Mouse Necrotizing Enterocolitis

2013 ◽  
Vol 182 (5) ◽  
pp. 1595-1606 ◽  
Author(s):  
Kelly R. Bergmann ◽  
Shirley X.L. Liu ◽  
Runlan Tian ◽  
Anna Kushnir ◽  
Jerrold R. Turner ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Necrotizing Enterocolitis ◽  
Intestinal Barrier ◽  
Barrier Dysfunction ◽  
Intestinal Barrier Dysfunction
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