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 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 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.

Abstract 645: Curcumin Modulates the Function(s) of Intestinal Epithelial Cells: Role in the Development of Diet-Induced Metabolic Diseases

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jing Wang ◽  
Siddhartha S Ghosh ◽  
Shobha Ghosh
Keyword(s):  
Epithelial Cells ◽  
Barrier Function ◽  
Metabolic Diseases ◽  
Intestinal Epithelial Cells ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Epithelial ◽  
Oral Supplementation ◽  
Pre Treatment ◽  
Induced Changes

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 into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. We demonstrated earlier that WD-induced changes in intestinal barrier function increases the release of LPS into systemic circulation and oral supplementation with curcumin not only reduces the levels of systemic LPS but also attenuates the subsequent development of glucose intolerance and atherosclerosis. Although curcumin is reported to exert potent anti-inflammatory effects in vitro , its poor bioavailability has raised doubts about a causal relationship between oral supplementation and the in vivo effects. It is hypothesized that curcumin attenuates WD-induced chronic inflammation and associated metabolic diseases by modulating the function of intestinal epithelial cells (IECs) and the objective of the present study was to delineate the underlying mechanisms. Human IEC lines, Caco-2, HT-29 and T-84 were used for these studies and modulation of direct as well as indirect effects of LPS on tight junctions as well as intracellular signaling were examined. Pre-treatment with Curcumin prevented LPS-induced disruption of tight junctions. LPS-induced secretion of master cytokine IL-1β was also dramatically reduced by pre-treatment with curcumin. Furthermore, curcumin also attenuated IL-1β induced activation of p-38 MAPK involved in the phosphorylation of tight junction proteins and subsequent disruption of their normal arrangement. Based on these data, the sites of curcumin actions leading to preservation of intestinal barrier function are shown in the Figure (activation and inhibition denoted by + and - symbols in green circles).

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 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 The Potential of Gut Commensals in Reinforcing Intestinal Barrier Function and Alleviating Inflammation

Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 988 ◽  
Author(s):  
Kaisa Hiippala ◽  
Hanne Jouhten ◽  
Aki Ronkainen ◽  
Anna Hartikainen ◽  
Veera Kainulainen ◽  
...  
Keyword(s):  
Barrier Function ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Intestinal Health ◽  
Beneficial Effects ◽  
Beneficial Action ◽  
Anti Inflammatory ◽  
Major Factors ◽  
Extracellular Structures

The intestinal microbiota, composed of pro- and anti-inflammatory microbes, has an essential role in maintaining gut homeostasis and functionality. An overly hygienic lifestyle, consumption of processed and fiber-poor foods, or antibiotics are major factors modulating the microbiota and possibly leading to longstanding dysbiosis. Dysbiotic microbiota is characterized to have altered composition, reduced diversity and stability, as well as increased levels of lipopolysaccharide-containing, proinflammatory bacteria. Specific commensal species as novel probiotics, so-called next-generation probiotics, could restore the intestinal health by means of attenuating inflammation and strengthening the epithelial barrier. In this review we summarize the latest findings considering the beneficial effects of the promising commensals across all major intestinal phyla. These include the already well-known bifidobacteria, which use extracellular structures or secreted substances to promote intestinal health. Faecalibacterium prausnitzii, Roseburia intestinalis, and Eubacterium hallii metabolize dietary fibers as major short-chain fatty acid producers providing energy sources for enterocytes and achieving anti-inflammatory effects in the gut. Akkermansia muciniphila exerts beneficial action in metabolic diseases and fortifies the barrier function. The health-promoting effects of Bacteroides species are relatively recently discovered with the findings of excreted immunomodulatory molecules. These promising, unconventional probiotics could be a part of biotherapeutic strategies in the future.

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