Effects of radio-frequency fields on bacterial cell membranes and nematode temperature-sensitive mutants

Membrane-related bioeffects have been reported in response to both radio-frequency (RF) and extremely low-frequency (ELF) electromagnetic fields (EMFs), particularly in neural cells. We have tested whether RF fields might cause inner membrane leakage in ML35 E. coli cells, which express β-galactosidase (lacZ) constitutively, but lack the lacY permease required for substrate entry. The activity of lacZ (indicating substrate leakage through the inner cell membrane) was increased only slightly by RF exposure (1 GHz, 0.5 W) over 45 min. Since lacZ activity showed no further increase with a longer exposure time of 90 min, this suggests that membrane permeability per se is not significantly affected by RF fields, and that slight heating (≤ 0.1°C) could account for this small difference. Temperature-sensitive (ts) mutants of the nematode, Caenorhabditis elegans, are wild-type at 15°C but develop the mutant phenotype at 25°C; an intermediate temperature of 21°C results in a reproducible mixture of both phenotypes. For two ts mutants affecting transmembrane receptors (TRA-2 and GLP-1), RF exposure for 24 h during the thermocritical phase strongly shifts the phenotype mix at 21°C towards the mutant end of the spectrum. For ts mutants affecting nuclear proteins, such phenotype shifts appear smaller (PHA-1) or non-significant (LIN-39), apparently confirming suggestions that RF power is dissipated mainly in the plasma membrane of cells. However, these phenotype shifts are no longer seen when microwave treatment is applied at 21°C in a modified exposure apparatus that minimises the temperature difference between sham and exposed conditions. Like other biological effects attributed to microwaves in the C. elegans system, phenotype shifts in ts mutants appear to be an artefact caused by very slight heating

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

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

Protective effect of quercetin treatment on HFD-induced intestinal dysbiosis and barrier dysfunction in an in vivo model of non-alcoholic fatty liver disease

1 p.Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Quercetin may have the ability to modulate the intestinal microbiota composition, suggesting therapeutic potential in NAFLD. The present study aims to investigate the beneficial effect of quercetin treatment on dysbiosis, intestinal barrier dysfunction and gut-liver axis alteration in high-fat diet (HFD)-fed mice. 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 Treatment on Gut Microbiota Imbalance in Obesity-Associated NAFLD in Patients and in HFD-FED Mice

2 p.Gut microbiota is involved in obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Quercetin may modulate the intestinal microbiota composition, suggesting therapeutic potential in NAFLD. The present study aims to establish the role of gut microbiota imbalance in obesity-related NAFLD development in patients and in an in vivo model and to investigate benefits of experimental treatment with quercetin. 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

Functional Interactions between Gut Microbiota Transplantation, Quercetin, and High‐Fat Diet Determine Non‐Alcoholic Fatty Liver Disease Development in Germ‐Free Mice

[EN] Scope: Modulation of intestinal microbiota has emerged as a new therapeutic approach for non-alcoholic fatty liver disease (NAFLD). Herein, it is addressed whether gut microbiota modulation by quercetin and intestinal microbiota transplantation can influence NAFLD development. Methods and results: Gut microbiota donor mice are selected according to their response to high-fat diet (HFD) and quercetin in terms of obesity and NAFLD-related biomarkers. Germ-free recipients displayed metabolic phenotypic differences derived from interactions between microbiota transplanted, diets, and quercetin. Based on the evaluation of hallmark characteristics of NAFLD, it is found that gut microbiota transplantation from the HFD-non-responder donor and the HFD-fed donor with the highest response to quercetin results in a protective phenotype against HFD-induced NAFLD, in a mechanism that involves gut–liver axis alteration blockage in these receivers. Gut microbiota from the HFD-responder donor predisposed transplanted germ-free mice to NAFLD. Divergent protective and deleterious metabolic phenotypes exhibited are related to definite microbial profiles in recipients, highlighting the predominant role of Akkermansia genus in the protection from obesity-associated NAFLD development. Conclusions: The results provide scientific support for the prebiotic capacity of quercetin and the transfer of established metabolic profiles through gut microbiota transplantation as a protective strategy against the development of obesity-related NAFLDSIM.V.G.M. and S.S.C. share senior authorship. D.P. and E.N. made equal contribution to the study. D.P., E.N., S.M.F., M.V.G.M., and S.S.C. performed most of the experiments. J.L.O. and F.J. performed statistical analysis. R.J. and J.G.G. assisted for in vivo models. S.S.C. designed the experiments and supervised the study. All the authors wrote the manuscript. The authors thank Drs. Gérard and Rabot, from MICALIS Institute (INRA), for providing germ-free mice. This work was supported by grants from Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (FEDER) (BFU2013-48141-R, BFU2017-87960-R), Junta de Castilla y León (LE135U13, GRS 1428/A/16), Junta de Castilla y León and FEDER, (LE063U16), and IIS Hospital La Fe (2017_0092_PP). D.P. was supported by a fellowship from Junta de Castilla y León co-financed by the European Social Fund. E.N. was supported by Fundación de Investigación Sanitaria of León. M.V.G.M. was supported by CIBERehd contracts. CIBERehd is funded by the Instituto de Salud Carlos III, Spai

Papel protector de Arkkemansia spp. frente al desarrollo NAFLD asociado a obesidad en ratones libres de gérmenes trasplantados con microbiota intestinal de donantes tratados con dieta rica en grasa y quercetina

El objetivo de este estudio es investigar el efecto protector del trasplante de microbiota y el uso del flavonol quercetina como prebiótico en ratones libres de gérmenes (GFm) en un modelo de NAFLD

Papel protector de Akkermansia SPP frente al desarrollo de NAFLD asociado a obesidad en ratones libres de gérmenes trasplantados con microbiata intestinal de donantes tratados con dieta rica en grasa y quercetina

2 p.Se pretende investigar el efecto protector del trasplante de microbiota y el uso del flavonol quercetina como prebiótico en ratones libres de gérmenes (GFm) en un modelo de NAFLD. 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

Efecto modulador de la quercetina sobre la disbiosis intestinal en un modelo animal de NAFLD asociada a obesidad

2 p.El estudio pretende investigar, en un modelo in vivo de NAFLD, el efecto beneficioso del tratamiento con quercetina sobre la disbiosis, la disfunción de la barrera intestinal y la alteración del eje intestinohígado inducido por una dieta rica en grasa (HFD). 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