Begomovirus quasispecies adapt to hosts by exploring different sequence space without changing their consensus sequences

Geminiviruses possess single-stranded circular DNA genomes that depend on cellular polymerases for replication in the host nucleus. In plant hosts, geminivirus populations behave as ensembles of mutant and recombinant genomes. This favours the emergence of new geminivirus strains able to produce new diseases or overcome the genetic resistance of cultivars. In warm and temperate areas several whitefly-transmitted geminiviruses of the genus Begomovirus cause the tomato yellow leaf curl disease (TYLCD) with important economic consequences. TYLCD is frequently controlled in commercial tomato production using the Ty-1 resistance gene. Over a 45 day period we studied the evolution of infectious clones from three TYLCD-associated begomoviruses: Tomato yellow leaf curl Sardinia virus, Tomato yellow leaf curl virus and the recombinant Tomato yellow leaf curl Axarquia virus. The evolution of their viral progeny was examined in susceptible tomato (ty1/ty1), resistant tomato (Ty1/ty1), common bean, and the wild reservoir Solanum nigrum. We found that in addition to affecting viral accumulation kinetics, the host influenced the sequence space explored by these begomoviruses. In tomato, viral dynamics was not influenced by the presence of the Ty-1 gene. Interestingly, positive adaptation of the coat protein gene was only observed in the common bean and S. nigrum, which correlates with these plants having viral quasispecies with the highest degree of complexity and heterogeneity. Our results underline the importance of analysing the mutant spectra of begomovirus infections, especially in wild reservoirs, which have the potential to give rise to large numbers of emergent variants in spite of the invariance of their consensus sequences.Junta de Andalucía proyecto: P10-CVI-6561. Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Flavonoids and Related Compounds in Non-Alcoholic Fatty Liver Disease Therapy

P. 2991-3012Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is one of the most common chronic liver diseases, which may progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD is characterized by the accumulation of lipids in the liver arising from multiple factors: increased fatty acid uptake, increased de novo lipogenesis, reduced fatty acid oxidation and very low density lipoproteins (VLDL) secretion. Most therapeutic approaches for this disease are often directed at reducing body mass index and improving insulin resistance through lifestyle modifications, bariatric surgery and pharmacological treatments. Nevertheless, there is increasing evidence that the use of natural compounds, as polyphenols, exert multiple benefits on the disorders associated with NAFLD. These molecules seem to be able to regulate the expression of genes mainly involved in de novo lipogenesis and fatty acid oxidation, which contributes to their lipid-lowering effect in the liver. Their antioxidant, anti-inflammatory, antifibrogenic and antilipogenic properties seem to confer on them a great potential as strategy for preventing NAFLD progression. In this review, we summarized the effects of these compounds, especially flavonoids, and their mechanisms of action, that have been reported in several studies carried out in in vitro and in vivo models of NAFL

Intestinal microbiota modulation in obesity-related non-alcoholic fatty liver disease

[EN] Obesity and associated comorbidities, including non-alcoholic fatty liver disease (NAFLD), are a major concern to public well-being worldwide due to their high prevalence among the population, and its tendency on the rise point to as important threats in the future. Therapeutic approaches for obesity-associated disorders have been circumscribed to lifestyle modifications and pharmacological therapies have demonstrated limited efficacy. Over the last few years, different studies have shown a significant role of intestinal microbiota (IM) on obesity establishment and NAFLD development. Therefore, modulation of IM emerges as a promising therapeutic strategy for obesity-associated diseases. Administration of prebiotic and probiotic compounds, fecal microbiota transplantation (FMT) and exercise protocols have shown a modulatory action over the IM. In this review we provide an overview of current approaches targeting IM which have shown their capacity to counteract NAFLD and metabolic syndrome features in human patients and animal models.SIThis work was supported by grants to JG-G and SS-C from Ministerio de Economía y Competitividad/FEDER (BFU2017- 87960-R) and Junta de Castilla y León (LE063U16 and GRS 1888/A/18). DP was supported by a fellowship from Junta de Castilla y León co-financed by the European Social Fund. EN was supported by Fundación de Investigación Sanitaria of León. MG-M was supported by CIBERehd contracts. CIBERehd is funded by the Instituto de Salud Carlos III, Spain

Intestinal microbiota transplantation to germ-free mice in a in vivo model of nafld associated with a quercetin treatment

15 p.To select mice donors for intestinal microbiota transplantation based on its metabolic phenotype in response to a high fat diet (HFD) and quercetin treatment (Q). Intestinal microbiota. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Intestinal Microbiota Transplantation From HFD-fed and Quercetin Treated Donors Results in a Complex Metabolic Phenotype Transfer that Modulates Obesity-Related NAFLD in Germ Free Mice

2 p.Intestinal microbiota imbalance and related gut-liver axis activation have been identified as key mechanisms in nonalcoholic fatty liver disease (NAFLD) development. Modulation of intestinal microbiota, through administration of prebiotics or faecal microbiota transplantation, is a promising therapeutic approach for obesity associated diseases including NAFLD. The aim of the present study is to evaluate the benefits of gut microbiota transplantation from donors to germ free mice (GFm) following an experimental treatment with the flavonoid quercetin in a high fat diet (HFD)-based NAFLD model. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation

60 p.Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-B signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid metabolism gene expression deregulation. Our results support the suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory, antioxidant and prebiotic integrative response.Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-B signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid metabolism gene expression deregulation. Our results support the suitability of quercetin as a therapeutic approach for obesity-associated NAFLD via its anti-inflammatory, antioxidant and prebiotic integrative respons

Akkermansia spp. mediates protection from obesity-associated NAFLD development in germ free mice following intestinal microbiota transplantation from high fat diet and quercetin treated donors

1 p.Dysbiosis and gut-liver axis alteration have been pointed as important contributors to obesity and non-alcoholic fatty liver disease (NAFLD) development. Modulation of intestinal microbiota (IM) emerge as a promising therapeutic strategy for obesity-associated NAFLD. This study aims to determine the effect of IM transplantation and quercetin supplementation in a high fat diet (HFD)-based NAFLD model in germ free mice (GFm). Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Metabolic Phenotype Transfer Through Gut Microbiota Transplantation from HFD-Fed and Quercetin Treated Donors Modulates Obesity-Related NAFLD in Germ-Free Mice

1 p.Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Strategies to modulate it, including faecal transplantation and administration of prebiotics as quercetin, are actively being examined. The present study aims to investigate benefits of experimental gut microbiota transfer from donors to germ-free mice (GFm) in a high-fat diet (HFD)-based NAFLD model. Resumen de un trabajo resultado del proyecto de investigación financiado por la Consejería de Educación de la Junta de Castilla y León (referencia LE063U16)S

Vascular Calcification and Oxidative DNA Damage as Nontraditional Cardiovascular Risk Factors in Chronic Renal Disease

The number of CKD sufferers that require renal replacement techniques (RRTs) is increasing. The severity of cardiovascular disease (CVD) is disproportionate in these kinds of patients and contributes considerably to mortality in CKD patients. We evaluated the association between oxidative DNA damage, antioxidant activity and vascular calcification (VC) in CKD. An analytical cross-sectional study was performed. Two simple plaques were taken for each patient (pelvis-hip, and hands-wrists). The presence of VC was scored as presence (1) and absence (0). Oxidative stress was determined by activity of catalase, superoxide dismutase (SOD) and oxidative DNA damage by determination of 8-OHdG marker. Eighty-one patients were included. The RRT type was similar for hemodialysis (HD) and peritoneal dialysis (PD). Thirty-eight patients (47%) presented VC (p < 0.01); in 61%, the VC was severe (≥3 points). VC prevalence in women was significantly higher, (67%) (p < 0.001), and (29%) men. Sixty four percent of the patients submitted to HD presented VC and 27% to PD (p < 0.001). The activity of the catalase enzyme was significantly decreased in CKD vs. the healthy control (HC) (p < 0.0001). The oxidative DNA damage in CKD was greater vs. HC (p < 0.0001). In conclusion, the VC was frequent (47%) in CKD, and decreased catalase activity and greater oxidative DNA damage