The epithelial barrier is the first innate defense of the gastrointestinal tract and selectively regulates transport from the lumen to the underlying tissue compartments, restricting the transport of smaller molecules across the epithelium and almost completely prohibiting epithelial macromolecular transport. This selectivity is determined by the mucous gel layer, which limits the transport of lipophilic molecules and both the apical receptors and tight junctional protein complexes of the epithelium. In vitro cell culture models of the epithelium are convenient, but as a model, they lack the complexity of interactions between the microbiota, mucous-gel, epithelium and immune system. On the other hand, in vivo assessment of intestinal absorption or permeability may be performed, but these assays measure overall gastrointestinal absorption, with no indication of site specificity. Ex vivo permeability assays using "intestinal sacs" are a rapid and sensitive method of measuring either overall intestinal integrity or comparative transport of a specific molecule, with the added advantage of intestinal site specificity. Here we describe the preparation of intestinal sacs for permeability studies and the calculation of the apparent permeability (Papp)of a molecule across the intestinal barrier. This technique may be used as a method of assessing drug absorption, or to examine regional epithelial barrier dysfunction in animal models of gastrointestinal disease. 相似文献
Trillions of microbes reside in the human body and participate in multiple physiological and pathophysiological processes that affect host health throughout the life cycle. The microbiome is hallmarked by distinctive compositional and functional features across different life periods.Accumulating evidence has shown that microbes residing in the human body may play fundamental roles in infant development and the maturation of the immune system. Gut microbes are thought to be essential for the facilitation of infantile and childhood development and immunity by assisting in breaking down food substances to liberate nutrients, protecting against pathogens, stimulating or modulating the immune system, and exerting control over the hypothalamic–pituitary–adrenal axis.This review aims to summarize the current understanding of the colonization and development of the gut microbiota in early life, highlighting the recent findings regarding the role of intestinal microbes in pediatric diseases. Furthermore, we also discuss the microbiota-mediated therapeutics that can reconfigure bacterial communities to treat dysbiosis. 相似文献
Intestinal cancer is a disease with high morbidity and high mortality in China. Previous studies have shown that Codonopsis foetens can inhibit cellular autophagy and promote the apoptosis of intestine cancer cells. Based on metabolomics method coupled with liquid chromatography-mass spectrometry (LC-MS) technology, we aimed to analyze intestinal small molecule metabolites in the intestinal cancer model group and the Codonopsis foetens treated group. Principal component analysis (PCA) and Partial Least Squares (PLS-DA) were used to identify the pattern of the data. And the metabolic characteristics of the cancer model group were explored based on the metabolic differences between the groups. Multivariate statistical analysis revealed that metabolites presented with differences included: Acetamide, Phosphoric acid, Hydrogen sulfite, Pyruvic acid, Cytosine, 2-Hydroxypyridine, Phosphoric acid, Uracil, Gamma-Aminobutyric acid, Glycerol alpha-monochlorohydrin, Thiosulfic acid, L-Valine, Cysteamine, Taurine, Creatine, Homocysteine, Hypoxanthine, Se-Methylselenocysteine, 5-Hydroxymethyluracil, Oxoglutaric acid, LysoPC(20:0), LysoPC(22:4(7Z,10Z,13Z,16Z)), LysoPC(18:2(9Z,12Z)), LysoPC(16:1(9Z)), LysoPE(0:0/16:0), LysoPE(0:0/18:2(9Z,12Z)), LysoPE(18:0/0:0), LysoPE(20:1(11Z)/0:0), etc. Combined with metabolic pathway analysis, pathways presented with differences included: Citrate cycle (TCA cycle), ABC transporters, 2-Oxocarboxylic acid metabolism, Taurine and hypotaurine metabolism, Butanoate metabolism), Phenylalanine, tyrosine and tryptophan biosynthesis, Biosynthesis of amino acids, Protein digestion and absorption, Aminoacyl-tRNA biosynthesis, C5-Branched dibasic acid metabolism, GABAergic synapse, Proximal tubule bicarbonate reclamation, Mineral absorption, Phenylalanine metabolism. The results showed that the proliferation of intestinal cancer cells caused cell metabolism disorders, manifesting as changes in metabolic pathways and resulting in changes in metabolites. 相似文献
The contribution of colostrum to passive immunity transfer and intestinal protection in newborn ruminants is well known; however, it is currently unclear how colostrum intake affects intestinal innate immunity. We investigated the effects of bovine colostrum intake on ileal morphology, expression of genes involved in intestinal innate immunity, and serum concentrations of inflammatory cytokines in newborn lambs. Twenty-seven newborn male Hu lambs were used, of which 18 were bottle-fed either bovine colostrum (C24h; n = 9) or bovine mature milk (M24h; n = 9) within the first 2 h after birth at an intake of approximately 8% of BW; the remaining nine lambs did not receive any feeding (N24h). Blood and ileal tissue samples were collected after the lambs were slaughtered at 24 h after birth. Ileal villus height and villus height-to-crypt depth ratio were significantly higher in C24h than those in N24h and M24h lambs (P < 0.01). Messenger RNA (mRNA) abundance of toll-like receptor (TLR)-2, TLR3, TLR4, TLR6, TLR7, TLR8 and tumour necrosis factor alpha in the ileum was lower in C24h than that in N24h lambs (P < 0.05). Moreover, C24h lambs had a lower TLR3 mRNA abundance (P < 0.01) and a trend of lower TLR6 (P = 0.06) and interleukin 1 beta (P = 0.08) expression compared with those in M24h lambs. We also observed strong positive correlations of tumour necrosis factor alpha expression with that of TLR2 (r = 0.71; P < 0.001), TLR4 (r = 0.88; P < 0.001) and TLR8 (r = 0.83; P < 0.001). Interestingly, the expression of barrier-related molecules, including mucin-13, lysozyme, claudin (CLDN)-1, CLDN2, CLDN4, CLDN7, CLDN12, occludin, zonula occluden-1 and junctional adhesion molecule-1, was consistently lower in C24h lambs than that in N24h and M24h lambs (P < 0.05). These results indicated that the beneficial roles of colostrum intake on intestinal protection in newborn lambs were associated with low TLR expression, which was reflected by improved intestinal development and reduced inflammatory response. Further studies using fluorescence in situ hybridisation and immunohistochemical methods are needed to further explore the mechanisms underlying the lower expression of intestinal barrier-related molecules due to colostrum feeding. 相似文献
Abstract To quantitate ammonia production by the intestinal flora, ammonia levels in arterial blood and the venous effluent of the small and large bowel of conventional, selectively decontaminated, germ-free and gnotobiotic rats were measured. When the anaerobic flora was removed by decontamination a significant decrease in ammonia levels was observed in the effluent of both the small and large intestine. Decontamination of aerobic flora did not result in depression of ammonia production. Gnotobiotic rats colonised with an anaerobic flora or with a mixed aerobic and anaerobic flora, showed a slight increase in ammonia levels. No increase in ammonia production was observed when rats were colonised with aerobic flora. These results indicate that the Enterobacteriaceae were not responsible for ammonia generation. The increase in ammonia levels after colonisation with anaerobic or mixed anaerobic/aerobic flora did not completely restore ammonia levels, despite reaching bacterial counts which were comparable to those in conventional rats. This may be explained by the limited number of species with which the rats were colonized. The finding that aerobic flora does not significantly contribute to ammonia production suggests that neomycin, known to be exclusively effective against aerobic flora, must have other effects to explain improvement of hepatic encephalopathy. 相似文献