Browsing by Author "Saavedra, Nicolas"
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Publication Characterization of microbial communities from gut microbiota of hypercholesterolemic and control subjects(2022) Morales, Cristian; Rojas, Gabriel; Rebolledo, Camilo; Rojas, Marcelo; Arias, Raúl; Cuadros, Sara; Maracaja, Vinicius; Saavedra, Kathleen; Leal, Pamela; Lanas, Fernando; Salazar, Luis; Saavedra, NicolasIntroduction: In recent years, several studies have evidenced the importance of the microbiome to host physiology as metabolism regulator, along with its potential role in triggering various diseases. In this study, we analyzed the gut microbiota in hypercholesterolemic (cases) and normocholesterolemic (controls) individuals to identify characteristic microbial signature for each condition. Methods: Stool samples were obtained from 57 adult volunteers (27 hypercholesterolemic and 30 controls). The taxonomic profiling of microbial communities was performed using high-throughput sequencing of 16S rRNA V3-V4 amplicons, followed by data analysis using Quantitative Insights Into Microbial Ecology 2 (QIIME2) and linear discriminant analysis (LDA) effect size (LEfSe). Results: Significant differences were observed in weight, height, body mass index (BMI) and serum levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol (LDL-C) between the groups (p<0.05). LEfSe showed differentially abundant prokaryotic taxa (α=0.05, LDA score > 2.0) in the group of hypercholesterolemic individuals (Methanosphaera, Rothia, Chromatiales, Clostridiales, Bacillaceae and Coriobacteriaceae) and controls (Faecalibacterium, Victivallis and Selenomonas) at various taxonomic levels. In addition, through the application of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2), the predominance of pathways related to biosynthesis in hypercholesterolemic patients was established, compared to controls in which degradation pathways were predominant. Finally, in the analysis of co-occurrence networks, it was possible to identify associations between the microorganisms present in both studied groups. Conclusion: Our results point out to unique microbial signatures, which likely play a role on the cholesterol metabolism in the studied population.Item Evaluation of the chemopreventive potentials of ezetimibeand aspirin in a novel mouse model of gallbladderpreneoplasia(2020) Rosa, Lorena; Lobos-González, Lorena; Munoz Durango, Natalia; Garcıa, Patricia; Bizama, Carolina; Gomez, Natalia; Gonzalez, Ximena; Wichmann, Ignacio A.; Saavedra, Nicolas; Guevara, Francisca; Villegas, Jaime; Arrese, Marco; Ferreccio, Catterina; Alexis M. Kalergis, Alexis M.; Miquel, Juan Francisco; Espinoza, Jaime A.; Roa, Juan C.Gallbladder stones (cholecystolithiasis) are the main risk factor for gallbladder cancer (GBC), a lethal biliary malignancy with poor survival rates worldwide. Gallbladder stones are thought to damage the gallbladder epithelium and trigger chronic inflammation. Preneoplastic lesions that arise in such an inflammatory microenvironment can eventually develop into invasive carcinoma, through mechanisms that are not fully understood. Here, we developed a novel gallbladder preneoplasia mouse model through the administration of two lithogenic diets (a low- or a high-cholesterol diet) in wild-type C57BL/6 mice over a period of 9 months. Additionally, we evaluated the chemopreventive potentials of the anti-inflammatory drug aspirin and the cholesterol absorption inhibitor ezetimibe. Both lithogenic diets induced early formation of gallbladder stones, together with extensive inflammatory changes and widespread induction of metaplasia, an epithelial adaptation to tissue injury. Dysplastic lesions were presented only in mice fed with high-cholesterol diet (62.5%) in late stages (9th month), and no invasive carcinoma was observed at any stage. The cholesterol absorption inhibitor ezetimibe inhibited gallbladder stone formation and completely prevented the onset of metaplasia and dysplasia in both lithogenic diets, whereas aspirin partially reduced metaplasia development only in the low-cholesterol diet setting. This model recapitulates several of the structural and inflammatory findings observed in human cholecystolithiasic gallbladders, making it relevant for the study of gallbladder carcinogenesis. In addition, our results suggest that the use of cholesterol absorption inhibitors and anti-inflammatory drugs can be evaluated as chemopreventive strategies to reduce the burden of GBC among high-risk populations.