Phenotyping of Fecal Microbiota of Winnie, a Rodent Model of Spontaneous Chronic Colitis, Reveals Specific Metabolic, Genotoxic, and Pro-inflammatory Properties

Abstract Winnie, a mouse carrying a missense mutation in the MUC2 mucin gene, is a valuable model for inflammatory bowel disease (IBD) with signs and symptoms that have multiple similarities with those observed in patients with ulcerative colitis. MUC2 mucin is present in Winnie, but is not firmly compacted in a tight inner layer. Indeed, these mice develop chronic intestinal inflammation due to the primary epithelial defect with signs of mucosal damage, including thickening of muscle and mucosal layers, goblet cell loss, increased intestinal permeability, enhanced susceptibility to luminal inflammation-inducing toxins, and alteration of innervation in the distal colon. In this study, we show that the intestinal environment of the Winnie mouse, genetically determined by MUC2 mutation, selects an intestinal microbial community characterized by specific pro-inflammatory, genotoxic, and metabolic features that could imply a direct involvement in the pathogenesis of chronic intestinal inflammation. We report results obtained by using a variety of in vitro approaches for fecal microbiota functional characterization. These approaches include Caco-2 cell cultures and Caco-2/THP-1 cell co-culture models for evaluation of geno-cytotoxic and pro-inflammatory properties using a panel of 43 marker RNAs assayed by RT-qPCR, and cell-based phenotypic testing for metabolic profiling of the intestinal microbial communities by Biolog EcoPlates. While adding a further step towards understanding the etiopathogenetic mechanisms underlying IBD, the results of this study provide a reliable method for phenotyping gut microbial communities, which can complement their structural characterization by providing novel functional information

Special Olympics swimming: positive effects on young people with Down syndrome

Purpose: The positive effects of sport and physical activity on health and well-being are worldwide recognized, while people with intellectual disabilities are often physically inactive. The aim of this study was to examine the perception of well-being, social integration, and emotional problems of Down syndrome (DS) subjects, who participated in Special Olympic (SO) training and competitions, and to investigate whether parents and their Down children have the same opinion on the problems caused by DS. Methods: Ninety-three participants with DS were recruited for this study: 58 swimmers (aged 16.31 ± 1.55), 35 DS sedentary subjects (aged 16.06 ± 1.39), and their parents (n = 93). Two versions of the Strengths and Difficulties Questionnaires (SDQ) were individually administered: the Self-reported version (SDQ-SR), completed by the DS participants, and the Parental version (SDQ-P), completed by their parents. Results: Results showed significant differences between sportive vs. non-sportive groups in the overall domain scores (p < 0.01), with better results for the sportive group. Parents of DS non-sportive participants underestimated their children problems in 6 of the 8 domains (p < 0.05). Conclusions: Participation in SO competition can be recommended to improve general well-being perception and social skills in young individuals with DS

The biochemical properties of the mitochondrial thiamine pyrophosphate carrier from Drosophila melanogaster

The mitochondrial carriers are a family of transport proteins that shuttle metabolites, nucleotides and cofactors across the inner mitochondrial membrane. The genome of Drosophila melanogaster encodes at least 46 members of this family. Only five of these have been characterized, whereas the transport functions of the remainder cannot be assessed with certainty. In the present study, we report the functional identification of two D. melanogaster genes distantly related to the human and yeast thiamine pyrophosphate carrier (TPC) genes as well as the corresponding expression pattern throughout development. Furthermore, the functional characterization of the D. melanogaster mitochondrial thiamine pyrophosphate carrier protein (DmTpc1p) is described. DmTpc1p was over-expressed in bacteria, the purified protein was reconstituted into liposomes, and its transport properties and kinetic parameters were characterized. Reconstituted DmTpc1p transports thiamine pyrophosphate and, to a lesser extent, pyrophosphate, ADP, ATP and other nucleotides. The expression of DmTpc1p in Saccharomyces cerevisiae TPC1 null mutant abolishes the growth defect on fermentable carbon sources. The main role of DmTpc1p is to import thiamine pyrophosphate into mitochondria by exchange with intramitochondrial ATP and ⁄ or ADP