Alcoholic liver disease and the gut-liver axis

Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.

Co-fermented defatted rice bran alters gut microbiota and improves growth performance,antioxidant capacity,immune status and intestinal permeability of finishing pigs

Based on preparation of co-fermented defatted rice bran(DFRB)using Bacillus subtilis,Saccharomyces cerevisiae,Lactobacillus plantarum and phytase,the present study aimed to evaluate the effects of cofermented DFRB on growth performance,antioxidant capacity,immune status,gut microbiota and permeability in finishing pigs.Ninety finishing pigs(85.30±0.97 kg)were randomly assigned to 3treatments(3 replicates/treatment)with a basal diet(Ctrl),a basal diet supplemented with 10% unfermented DFRB(UFR),and a basal diet supplemented with 10% fermented DFRB(FR)for 30 d.Results revealed that the diet supplemented with FR notably(P<0.05)improved the average daily gain(ADG),gain to feed ratio(G:F)and the digestibility of crude protein,amino acids and dietary fiber of finishing pigs compared with UFR.Additionally,FR supplementation significantly(P<0.05)increased total antioxidant capacity,the activities of superoxide dismutase and catalase,and decreased the content of malonaldehyde in serum.Furthermore,FR remarkably(P<0.05)increased serum levels of Ig G,antiinflammatory cytokines(IL-22 and IL-23)and reduced pro-inflammatory cytokines(TNF-α,IL-1β and INF-γ).The decrease of serum diamine oxidase activity and serum D-lactate content in the FR group(P<0.05)suggested an improvement in intestinal permeability.Supplementation of FR also elevated the content of acetate and butyrate in feces(P<0.05).Moreover,FR enhanced gut microbial richness and the abundance of fiber-degrading bacteria such as Clostridium butyricum and Lactobacillus amylovorus.Correlation analyses indicated dietary fiber in FR was associated with improvements in immune status,intestinal permeability and the level of butyrate-producing microbe C.butyricum,which was also verified by the in vitro fermentation analysis.These findings provided an experimental and theoretical basis for the application of fermented DFRB in finishing pigs.

Gracilaria fisheri oligosaccharides ameliorate inflammation and colonic epithelial barrier dysfunction in mice with acetic acid-induced colitis

Objective:To investigate the effect of Gracilaria fisheri oligosaccharides(GFO)on inflammation and colonic epithelial barrier dysfunction in colitis mice.Methods:The animals were treated by oral gavage with distilled water,1000 mg/kg inulin,100,500,or 1000 mg/kg GFO for 14 d,or treated with 50 mg/kg mesalamine for 5 d after colitis induction(on day 10).Histopathology,inflammatory cytokines,colonic permeability,and tight junction proteins were investigated by hematoxylin and eosin staining,immunohistochemical staining,Ussing chamber technique,and Western blotting assays,respectively.Results:GFO ameliorated histological damage in colitis mice when compared to untreated colitis mice.Treatments with 100,500,and 1000 mg/kg GFO reduced TNF-αexpression,while IL-1βwas significantly reduced in colitis mice treated with 500 and 1000 mg/kg.Compared to untreated colitis mice,GFO increased transepithelial electrical resistance,reduced fluorescein isothiocyanate-dextran paracellular flux,and modulated tight junction proteins(occludin and claudin 2)in colitis mice.Conclusions:GFO has anti-inflammatory activity and could modulate colonic epithelial barrier dysfunction in acetic acid-induced colitis mice.Furthermore,GFO could modulate the expression of tight junction proteins that play important roles in colonic barrier function.

Intestinal mucosal barrier in functional constipation:Dose it change?

BACKGROUND The intestinal mucosal barrier is the first line of defense against numerous harmful substances,and it contributes to the maintenance of intestinal homeostasis.Recent studies reported that structural and functional changes in the intestinal mucosal barrier were involved in the pathogenesis of several intestinal diseases.However,no study thoroughly evaluated this barrier in patients with functional constipation(FC).AIM To investigate the intestinal mucosal barrier in FC,including the mucus barrier,intercellular junctions,mucosal immunity and gut permeability.METHODS Forty FC patients who fulfilled the Rome IV criteria and 24 healthy controls were recruited in the Department of Gastroenterology of China-Japan Friendship Hospital.The colonic mucus barrier,intercellular junctions in the colonic epithelium,mucosal immune state and gut permeability in FC patients were comprehensively examined.Goblet cells were stained with Alcian Blue/Periodic acid Schiff(AB/PAS)and counted.The ultrastructure of intercellular junctional complexes was observed under an electron microscope.Occludin and zonula occludens-1(ZO-1)in the colonic mucosa were located and quantified using immunohistochemistry and quantitative real-time polymerase chain reaction.Colonic CD3+intraepithelial lymphocytes(IELs)and CD3+lymphocytes in the lamina propria were identified and counted using immunofluorescence.The serum levels of D-lactic acid and zonulin were detected using enzyme-linked immunosorbent assay.RESULTS Compared to healthy controls,the staining of mucus secreted by goblet cells was darker in FC patients,and the number of goblet cells per upper crypt in the colonic mucosa was significantly increased in FC patients(control,18.67±2.99;FC,22.42±4.09;P=0.001).The intercellular junctional complexes in the colonic epithelium were integral in FC patients.The distribution of mucosal occludin and ZO-1 was not altered in FC patients.No significant differences were found in occludin(control,5.76E-2±1.62E-2;FC,5.17E-2±1.80E-2;P=0.240)and ZO-1(control,2.29E-2±0.93E-2;FC,2.68E-2±1.60E-2;P=0.333)protein expression between the two groups.The mRNA levels in occludin and ZO-1 were not modified in FC patients compared to healthy controls(P=0.145,P=0.451,respectively).No significant differences were observed in the number of CD3+IELs per 100 epithelial cells(control,5.62±2.06;FC,4.50±2.16;P=0.070)and CD3+lamina propria lymphocytes(control,19.69±6.04/mm^(2);FC,22.70±11.38/mm^(2);P=0.273).There were no significant differences in serum D-lactic acid[control,5.21(4.46,5.49)mmol/L;FC,4.63(4.31,5.42)mmol/L;P=0.112]or zonulin[control,1.36(0.53,2.15)ng/mL;FC,0.94(0.47,1.56)ng/mL;P=0.185]levels between FC patients and healthy controls.CONCLUSION The intestinal mucosal barrier in FC patients exhibits a compensatory increase in goblet cells and integral intercellular junctions without activation of mucosal immunity or increased gut permeability.