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.

Vitamin A deficiency suppresses CEACAM1 to impair colonic epithelial barrier function via downregulating microbial-derived short-chain fatty acids

Vitamin A (VA) plays an essential role in modulating both the gut microbiota and gut barrier function.Short-chain fatty acids (SCFAs),as metabolites of the gut microbiota,protect the physiological intestinal barrier;however,they are compromised when VA is deficient.Thus,there is an urgent need to understand how and which SCFAs modulate colonic epithelial barrier integrity in VA deficiency (VAD).Herein,compared with normal VA rats (VAN),at the beginning of pregnancy,we confirmed that the colonic desmosome junction was impaired in the VAD group,and the amounts of acetate,propionate,and butyrate declined because of the decreased abundance of SCFA-producing bacteria (Romboutsia ,Collinsella ,and Allobaculum ).The differentially expressed genes correlated with the gut barrier and the histone deacetylase complex between the VAD and VAN groups were enriched by RNA sequencing.In the VAD group,the expression levels of colonic CEA cell adhesion molecule 1 (CEACAM1) were down-regulated,and the levels of histone deacetylase 1 (HDAC1) and HDAC3 were up-regulated.Intriguingly,the above changes in the VAD groups were rescued by VA supplementation in the early postnatal period.Further study indicated that in Caco-2 cells,butyrate treatment significantly repressed the enrichment of HDAC3 on the promoter of the CEACAM1 gene to induce its expression.Our findings support that butyrate intervention can alleviate the impairment of colonic barrier function caused by VAD,and timely postnatal VA intervention may reverse the damage caused by VAD on gut barrier integrity during pregnancy.