Celiac disease (CD) is a chronic immune-mediated disorder, characterized by enhanced paracellular permeability across the intestinal epithelium. The complex system of intercellular junctions, including tight junctions (TJs) and adherens junctions (AJs), seals together the epithelial cells to form a continuous layer. The improvements in barrier integrity have been related to modifications in intercellular junction protein expression. Polyamines (spermidine, spermine, and putrescine) actively participate in the modulation of the AJ expression. Both in vitro and in vivo studies have demonstrated that also probiotics can promote the integrity and the function of the intestinal barrier. On these bases, the present work investigated the protective effects exerted by Lactobacillus rhamnosus GG (L.GG) against the pepsin-trypsin-digested gliadin (PTG)-induced enteropathy in jejunal tissue samples of Wistar rats. In particular, the probiotic effects have been evaluated on the intestinal mucosal architecture, polyamine metabolism and intercellular junction protein expression (ZO-1, Occludin, Claudin-1, β-catenin and E-cadherin). The results from this study indicate that L.GG protects the intestinal mucosa of rats from PTG-induced damage, by preventing the reduction of the expression of the intercellular junction proteins. Consequently, a role for L.GG in the therapeutic management of the gluten-related disorders in humans could be hypothesized.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation associated with an increased intestinal permeability. Several studies have shown that microRNAs (miRNAs) are involved in the IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of intestinal permeability and barrier function. We identified 18 dysregulated miRNAs in intestinal epithelial cells (IECs) from the ulcerative colitis (UC) mice model and control mice. Among them, down-regulated miR-195-5p targeted claudin-2 (CLDN2) and was involved in impaired barrier function. CLDN2 expression levels were increased in UC mice models and negatively correlated with miR-195-5p expression. We demonstrated that gain-of-function of miR-195-5p in colonic epithelial cell lines decreased the CLDN2 levels. This modulation, in turn, downregulated claudin-1 (CLDN1) expression at protein level but not that of occludin. Our data support a previously unreported role of miR-195-5p in intestinal tight junctions’ regulation and suggest a potential pharmacological target for new therapeutic approaches in IBD.

(1) Background: Colorectal cancer (CRC) is among the best examples of the relationship between inflammation and increased cancer risk. (2) Methods: To examine the effects of spontaneous low-grade chronic inflammation on the pathogenesis of CRC, we developed a new murine model of colitis-associated cancer (CAC) by crossing Mucin 2 mutated mice (Winnie) with Apc^Min/+ mice. (3) Results: The resulting Winnie-Apc^Min/+ model combines an inflammatory background with a genetic predisposition to small intestinal polyposis. Winnie-Apc^Min/+ mice show an early occurrence of inflammatory signs and dysplastic lesions in the distal colon with a specific molecular signature. (4) Conclusion: The Winnie-Apc^Min/+ model is a perfect model to demonstrate that chronic inflammation represents a crucial risk factor for the onset and progression of tumoral lesions in individuals genetically predisposed to CRC.

The statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and orlistat, an inhibitor of fatty acid synthase (FAS), inhibit tumor cell growth by restricting cholesterol and fatty acid synthesis, respectively. We previously demonstrated that an omega (ω)-3 polyunsaturated fatty acid (PUFA)- or olive oil-enriched diet reduced the polyp number and volume in ApcMin/+ mice. This phenomenon was associated with a significant inhibition of FAS and HMGCoAR, as well as an increase in the estrogen receptor (ER)β/α ratio. Herein, we evaluated the effect of lovastatin and orlistat on polyp development and ER expression in ApcMin/+ mice, in order to confirm previous data obtained with ω‑3-PUFAs and olive oil. As expected, the use of lovastatin and orlistat significantly reduced HMGCoAR and FAS enzymatic activities and gene expression in colonic tissues, but did not affect the number of intestinal polyps, while there was a statistically significant reduction in polyp volume only in the mouse group treated with lovastatin. In the mice receiving orlistat, we observed a significant increase in cell proliferation in the polyp tissue, as well as enhanced expression of ERα. Moreover, the overexpression of ERα was associated with a statistically significant increase in PES1, Shh and Gli1 protein levels, considered ERα-related molecular targets.