Regulation of TWlK-related potassium channel- 1 （Trek1） restitutes intestinal epithelial barrier function

The disruption of epithelial barrier integrity is an important factor in the pathogenesis of various immune disorders. However, the restitution of the compromised barrier functions is difficult. This study investigates the regulation of TWIK-related potassium channel-1 （Trek1） in the restitution of intestinal epithelial barrier functions. The human colon epithelial cell line T84 was cultured in monolayers and used to observe epithelial barrier functions in vitro. An intestinal allergy mouse model was created. Cytokine levels were determined by enzyme-linked immunosorbent assay and western blotting. The results showed that Trek1 deficiency induced T84 monolayer barrier disruption. Allergic responses markedly suppressed the expression of Trek1 in the intestinal epithelia via activating the mitogen-activated protein kinase pathways and increasing the expression of histone deacetylase-1. The inhibition of histone deacetylase-1 by sodium butyrate or the administration of a butyrate-producing probiotic （Clostridium butyricum） restored the intestinal epithelial barrier functions and markedly enhanced the effect of antigen-specific immunotherapy. The data suggest that Trek1 is required for the maintenance of intestinal epithelial barrier integrity. Allergic responses induce an insufficiency of Trek1 expression in the intestinal epithelia. Trek1 expression facilitates the restoration of intestinal epithelial barrier functions in an allergic environment.

Role of omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes on intestinal barrier integrity and immunity in animals

The gastrointestinal tract of livestock and poultry is prone to challenge by feedborne antigens,pathogens,and other stress factors in the farm environment.Excessive physiological inflammation and oxidative stress that arises firstly disrupts the intestinal epithelial barrier followed by other components of the gastrointestinal tract.In the present review,the interrelationship between intestinal barrier inflammation and oxidative stress that contributes to the pathogenesis of inflammatory bowel disease was described.Further,the role of naturally existing immunomodulatory nutrients such as the omega-3 polyunsaturated fatty acids,citrus pectin,and milk-derived exosomes in preventing intestinal barrier inflammation was discussed.Based on the existing evidence,the possible molecular mechanism of these bioactive nutrients in the intestinal barrier was outlined for application in animal diets.

Lonicera caerulea polyphenols inhibit fat absorption by regulating Nrf2-ARE pathway mediated epithelial barrier dysfunction and special microbiota

Scope:High-fat diet(HFD)induces imbalance in the small intestine environment,where fat digestion and absorption mainly take place.This study aimed to elucidate the mechanisms by which Lonicera caerulea polyphenols(LCP)might inhibit fat absorption,from the perspective of small intestine microbiota and epithelial barrier integrity.Methods and results:Male Sprague-Dawley rats were given HFD with or without co-administration of LCP for 8 weeks.The results showed that LCP supplementation significantly decreased the levels of serum triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C),and increased the contents of fecal sterols,in HFD rats.LCP also inhibited the dysfunction of the small intestine epithelial barrier,via alleviating the oxidative stress activated by Nrf2-ARE pathway,and by modulating the expressions of pro-inflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),cyclooxygenase-2(COX-2),nuclear factor kappa-B p65(NF-κB p65)and inducible nitric oxide synthase(iNOS)in the small intestine.Additionally,LCP administration restored the balance in small intestine microbiota and increased the abundance of the specific bacteria,such as Lactobacillus,involved in fat absorption.Conclusion:Our results demonstrated that LCP may be beneficial to inhibit fat absorption.The mechanism seems to be associated with the protection of the epithelial barrier integrity and the modulation of specific bacteria in the small intestine.

Research progress on the relationship between intestinal microecology and intestinal bowel disease

Intestinal microecology is the main component of human microecology.Intestinal microecology consists of intestinal microbiota,intestinal epithelial cells,and intestinal mucosal immune system.These components are interdependent and establish a complex interaction network that restricts each other.According to the impact on the human body,there are three categories of symbiotic bacteria,opportunistic pathogens,and pathogenic bacteria.The intestinal microecology participates in digestion and absorption,and material metabolism,and inhibits the growth of pathogenic microorganisms.It also acts as the body’s natural immune barrier,regulates the innate immunity of the intestine,controls the mucosal barrier function,and also participates in the intestinal epithelial cells’physiological activities such as hyperplasia or apoptosis.When the steady-state balance of the intestinal microecology is disturbed,the existing core intestinal microbiota network changes and leads to obesity,diabetes,and many other diseases,especially irritable bowel syndrome,inflammatory bowel disease(IBD),and colorectal malignancy.Intestinal diseases,including tumors,are particularly closely related to intestinal microecology.This article systematically discusses the research progress on the relationship between IBD and intestinal microecology from the pathogenesis,treatment methods of IBD,and the changes in intestinal microbiota.

Multispecies probiotic protects gut barrier function in experimental models

AIM: To investigate the effect of the probiotic combination Lactibiane Tolerance® (LT) on epithelial barrier function in vitro and in vivo.

Regulatory effects of the p38 mitogen-activated protein kinase-myosin light chain kinase pathway on the intestinal epithelial mechanical barrier and the mechanism of modified Pulsatilla decoction(加味白头翁汤)in the treatment of ulcerative colitis

OBJECTIVE:To investigate the mechanism of the protective effect of modified Pulsatilla decoction(加味白头翁汤,MPD)on the mechanical barrier of the ulcerative colitis(UC)intestinal epithelium in vitro and in vivo.METHODS:We established an intestinal epithelial crypt cell line-6 cell barrier injury model by using lipopolysaccharide(LPS).The model was then treated with p38 mitogen-activated protein kinase-myosin light chain kinase(p38MAPK-MLCK)pathway inhibitors,p38MAPK-MLCK pathway silencing genes(si-p38MAPK,si-NF-κB,and si-MLCK),and MPD respectively.Transepithelial electronic resistance(TEER)measurements and permeability assays were performed to assess barrier function.Immunofluorescence staining of tight junctions(TJ)was performed.In in vivo experiment,dextran sodium sulfate-induced colitis rat model was conducted to evaluate the effect of MPD and mesalazine on UC.The rats were scored using the disease activity index based on their clinical symptoms.Transmission electron microscopy and hematoxylineosin staining were used to examine morphological changes in UC rats.Western blotting and real-time quantitative polymerase chain reaction were performed to examine the gene and protein expression of significant differential molecules.RESULTS:In in vitro study,LPS-induced intestinal barrier dysfunction was inhibited by p38MAPK-MLCK pathway inhibitors and p38MAPK-MLCK pathway gene silencing.Silencing of p38MAPK-MLCK pathway genes decreased TJ expression.MPD treatment partly restored the LPSinduced decreased in TEER and increase in permeability.MPD increased the gene and protein expression of TJ,while down-regulated the LPS-induced high expression of p-p38MAPK and p-MLC.In UC model rats,MPD could ameliorate body weight loss and disease activity index,relieve colonic pathology,up-regulate TJ expression as well as decrease the expression of p-p38MAPK and pMLC in UC rat colonic mucosal tissue.CONCLUSIONS:The p38MAPK-MLCK signaling pathway can affect mechanical barrier function and TJ expression in the intestinal epithelium.MPD restores TJ expression and attenuates intestinal epithelial barrier damage by suppressing the p38MAPK-MLCK pathway.

Isolation and characterization of novel peptides from fermented products of Lactobacillus for ulcerative colitis prevention and treatment

Ulcerative colitis(UC)is an incurable and highly complex digestive disease affecting millions of people worldwide.Compared to the current therapeutic drugs,bioactive peptides are more promising and safe substances as functional foods or drugs for the prevention and treatment of UC.The alcohol-soluble components from fermentation broth by fresh wheat germ and apple(AC-WGAF)were found to be effective in UC prevention in dextran sulfate sodium-induced mice in vivo.Herein,4 novel peptides are identifi ed from AC-WGAF by membrane ultrafi ltration,recycling preparative high-performance liquid chromatography,and matrix-assisted laser desorption–ionization time-of-fl ight/time-of-fl ight mass spectrometry,possessing anticolitis activity via using an in vitro model.One of those peptides named T24(PVLGPVRGPFPLL)exhibited the most remarkable anti-colitis activity by preventing tight junction protein loss,maintaining epithelial barrier integrity,and promoting cell proliferation during in vitro and in vivo studies by regulating mitogen-activated protein kinase signaling pathways.Thus,T24 is a promising peptide as a functional food or novel drug for UC prevention and treatment.

Loss of T-cell protein tyrosine phosphatase in the intestinal epithelium promotes local inflammation by increasing colonic stem cell proliferation

T-cell protein tyrosine phosphatase(TC-PTP)has a critical role in the development of the immune system and has been identified as a negative regulator of inflammation.Single-nucleotide polymorphisms in the TC-PTP locus have been associated with increased susceptibility to inflammatory bowel diseases(IBDs)in patients.To further understand how TC-PTP is related to IBDs,we investigated the role of TC-PTP in maintaining the intestinal epithelial barrier using an in vivo genetic approach.Intestinal epithelial cell(IEC)-specific deletion of TC-PTP was achieved in a mouse model at steady state and in the context of dextran sulphate sodium(DSS)-induced colitis.Knockout(KO)of TC-PTP in IECs did not result in an altered intestinal barrier.However,upon DSS treatment,IECspecific TC-PTP KO mice displayed a more severe colitis phenotype with a corresponding increase in the immune response and inflammatory cytokine profile.The absence of TC-PTP caused an altered turnover of IECs,which is further explained by the role of the tyrosine phosphatase in colonic stem cell(CoSC)proliferation.Our results suggest a novel role for TC-PTP in regulating the homeostasis of CoSC proliferation.This supports the protective function of TC-PTP against IBDs,independently of its previously demonstrated role in intestinal immunity.