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, 1 000 mg/kg inulin, 100, 500, or 1 000 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 1 000 mg/kg GFO reduced TNF-α expression, while IL-1β was significantly reduced in colitis mice treated with 500 and 1 000 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.

Effect of nuciferine on gut microbiota and inflammatory response in obese model mice / 中国中药杂志

The aim of this study was to elucidate the mechanism of nuciferine on alleviating obesity based on modulating gut microbiota, ameliorating chronic inflammation, and improving gut permeability. In this study, the obese model mice were induced by high-fat diet and then randomly divided into model group, and nuciferine group; some other mice of the same week age were fed with normal diet as normal group. In the modeling process, the mice were administered intragastrically(ig) for 12 weeks. In the course of both modeling and treatment, the body weight and food intake of mice in each group were measured weekly. After modeling and treatment, the Lee's index, weight percentage of inguinal subcutaneous fat, and the level of blood lipid in each group were measured. The pathological changes of adipocytes were observed by HE staining to evaluate the efficacy of nuciferine treatment in obese model mice. 16 S rRNA sequencing analysis was conducted to study the changes in diversity and abundance of gut microbiota after nuciferine treatment. Enzyme-linked immunosorbent assay(ELISA) and quantitative Real-time polymerase chain reaction(qPCR) were used to detect the levels of inflammatory factors interleukin-6(IL-6), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α) and the expression of related genes in adipose tissue of mice in each group, so as to evaluate the effect of nuciferine on chronic inflammation of mice in obese model group. qPCR was used to detect the expression of occludin and tight junction protein 1(ZO-1)gene in colon tissure, so as to evaluate the effect of nuciferine on intestinal permeability of mice in obese group. Nuciferine decreased the body weight of obese mice, Lee's index, weight percentage of inguinal subcutaneous fat(P<0.05), and reduced the volume of adipocytes, decreased the level of total cholesterol(TC), triglyceride(TG), and low density lipoprotein cholesterol(LDL-C)(P<0.05) in serum, improved dysbacteriosis, increased the relative abundance of Alloprevotella, Turicibacter, and Lactobacillus, lowered the relative abundance of Helicobac-ter, decreased the expression of inflammatory cytokines IL-6, IL-1β, and TNF-α genes in adipose tissue(P<0.01), decreased the levels of inflammatory cytokines IL-6, IL-1β, and TNF-α in serum(P<0.05), and increased the expression of occludin and ZO-1 genes related to tight junction in colon tissue(P<0.01). Nuciferine could treat obesity through modulating gut microbiota, decreasing gut permeability and ameliorating inflammation.

Probiotics as Complementary Treatment for Metabolic Disorders

Over the past decade, growing evidence has established the gut microbiota as one of the most important determinants of metabolic disorders such as obesity and type 2 diabetes. Indeed, obesogenic diet can drastically alter bacterial populations (i.e., dysbiosis) leading to activation of pro-inflammatory mechanisms and metabolic endotoxemia, therefore promoting insulin resistance and cardiometabolic disorders. To counteract these deleterious effects, probiotic strains have been developed with the aim of reshaping the microbiome to improve gut health. In this review, we focus on benefits of widely used probiotics describing their potential mechanisms of action, especially their ability to decrease metabolic endotoxemia by restoring the disrupted intestinal mucosal barrier. We also discuss the perspective of using new bacterial strains such as butyrate-producing bacteria and the mucolytic Akkermansia muciniphila, as well as the use of prebiotics to enhance the functionality of probiotics. Finally, this review introduces the notion of genetically engineered bacterial strains specifically developed to deliver anti-inflammatory molecules to the gut.

A study of mesenchymal stem cells decreasing intestinal permeability induced by mesenteric ischemia/reperfusion / 肠外与肠内营养

Objective: To investigate the effect of bone marrow mesenchymal stem cells (MSC) on the variation of intestinal permeability damaged by superior mesenteric artery ischemia and reperfusion. Methods: Bone marrow mesenchymal stem cells were isolated from cavity of tibias and femurs of male Sprague Dawley rat in a sterile condition, and were cultured and proliferated in plastic dishes. 10 week old female Sprague Dawley rats were randomly divided into three groups:group A (sham group), group B (MSC group) and group C (saline group). In group B and group C, the superior mesenteric artery (SMA) of the animals were seperated and occluded by non-invasive vascular clamp for 45 minutes. Immediately after removing the vascular clamp,1×10~7 MSC suspended in 0.5 ml sterile L-DMEM and the same volume of normal saline was submucosally injected into the small intestine at ten different points in group B and group C, respectively. In group A, the animals were only underwent laparotomy without clamping the SMA. 3 days and 6 days after the operation, 100 mg lactulose and 50mg mannitol dissolved in 2 ml distilled water were administrated by oral gavage and urine during 6 h experiment was collected for assaying the L/M ratio before sacrificing the animals. The donor derived MSC was identified by Y chromosome in situ hybridization in ileum tissue, and the serum D-lactate level was determined. Results: The donor derived MSC could home to the ischemia/reperfusion injured intestinal mucosa, and the intestinal permeability was much lower in group B (MSC group) than that in group C (saline group)(P<0.05). Conclusion: Mesenchymal stem cells can reduce the small intestinal mucosal permeability impaired by ischemia/reperfusion, and can participate in the preservation of integrity of the damaged gut mucosal mechanical barrier.