scholarly journals Intestinal Barrier Function – a Novel Target to modulate Diet-induced Metabolic Diseases

2020 ◽  
Vol 1 (3) ◽  
Keyword(s):  
Barrier Function ◽  
Metabolic Diseases ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Novel Target

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.

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.

Butyrate as a Potential Preventive Therapy for Obesity

2019 ◽  
Vol 56 (4) ◽  
pp. 439
Author(s):  
P. Meena Kumari ◽  
S. P. Muthukumar
Keyword(s):  
Barrier Function ◽  
Inflammatory Mediator ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Low Grade ◽  
Metabolic Risk ◽  
Metabolic Complications ◽  
Anti Inflammatory

Due to its grave pathological role of obesity, comprehensive research is being continued to find out the causative factors involved in it. Recent advances in this field are increasingly recognized that there is a connection between diet, gut microbiota, intestinal barrier function and the low-grade inflammation that characterize the progression from obesity to metabolic disturbances, making dietary strategies to modulate the intestinal environment is important. In this context, the ability of some Gram-positive anaerobic bacteria to produce the shortchain fatty acid butyrate is impressive. A lower abundance of butyrate-producing bacteria has been associated with metabolic risk in humans. Recent studies suggest that butyrate might have been linked with metabolic risk in humans, and recommend that butyrate might have an anti-inflammatory mediator in metabolic diseases, and the potential of butyrate can alleviate obesity-related metabolic complications, possibly due to its ability to enhance the intestinal barrier function. Endogenous butyrate synthesis, delivery, and absorption by colonocytes have been well studied. Butyrate exerts its function by serving as a histone deacetylase (HDAC) inhibitor or signaling through several G Protein-Coupled Receptors (GPCRs). Latterly butyrate has gained selective attention for its favorable effects on intestinal homeostasis and energy metabolism. With anti-inflammatory properties, butyrate improves intestinal barrier function and mucosal immunity. Growing proof has highlighted the influence of butyrate on obesity. In this review the current knowledge on the features of butyrate, especially its potential effects and mechanisms involved in intestinal health and obesity. Here we review and discuss the potentials of butyrate as an anti-inflammatory mediator in obesity and the potential for dietary interventions increasing intestinal availability of butyrate.

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).

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 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 Somatization in patients with predominant diarrhoea irritable bowel syndrome: the role of the intestinal barrier function and integrity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Laura Prospero ◽  
Giuseppe Riezzo ◽  
Michele Linsalata ◽  
Antonella Orlando ◽  
Benedetta D’Attoma ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Barrier Function ◽  
Rating Scale ◽  
Psychological Symptoms ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Fatty Acid Binding ◽  
Gastrointestinal Symptom Rating Scale ◽  
Gi Symptoms ◽  
Irritable Bowel

Abstract Background Irritable bowel syndrome (IBS) is characterised by gastrointestinal (GI) and psychological symptoms (e.g., depression, anxiety, and somatization). Depression and anxiety, but not somatization, have already been associated with altered intestinal barrier function, increased LPS, and dysbiosis. The study aimed to investigate the possible link between somatization and intestinal barrier in IBS with diarrhoea (IBS-D) patients. Methods Forty-seven IBS-D patients were classified as having low somatization (LS = 19) or high somatization (HS = 28) according to the Symptom Checklist-90-Revised (SCL-90-R), (cut-off score = 63). The IBS Severity Scoring System (IBS-SSS) and the Gastrointestinal Symptom Rating Scale (GSRS) questionnaires were administered to evaluate GI symptoms. The intestinal barrier function was studied by the lactulose/mannitol absorption test, faecal and serum zonulin, serum intestinal fatty-acid binding protein, and diamine oxidase. Inflammation was assessed by assaying serum Interleukins (IL-6, IL-8, IL-10), and tumour necrosis factor-α. Dysbiosis was assessed by the urinary concentrations of indole and skatole and serum lipopolysaccharide (LPS). All data were analysed using a non-parametric test. Results The GI symptoms profiles were significantly more severe, both as a single symptom and as clusters of IBS-SSS and GSRS, in HS than LS patients. This finding was associated with impaired small intestinal permeability and increased faecal zonulin levels. Besides, HS patients showed significantly higher IL-8 and lowered IL-10 concentrations than LS patients. Lastly, circulating LPS levels and the urinary concentrations of indole were higher in HS than LS ones, suggesting a more pronounced imbalance of the small intestine in the former patients. Conclusions IBS is a multifactorial disorder needing complete clinical, psychological, and biochemical evaluations. Trial registration: https://clinicaltrials.gov/ct2/show/NCT03423069.

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