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Project Q3134933 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | No label defined |
Project Q3134933 in Spain |
Statements
48,400.0 Euro
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96,800.0 Euro
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50.0 percent
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1 January 2018
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31 December 2020
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UNIVERSIDAD DE LEON
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24089
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LA ENFERMEDAD DE HIGADO GRASO NO ALCOHOLICO (NAFLD) ES UNA DE LAS CAUSAS MAS COMUNES DE ENFERMEDAD HEPATICA EN ESPAÑA. EN LA PATOGENESIS DE NAFLD SE COMBINAN EL ESTRES OXIDATIVO, LA DESREGULACION DEL METABOLISMO LIPIDICO, LA INFLAMACION, LA ALTERACION DE LA MICROBIOTA INTESTINAL (DISBIOSIS) Y LA ACTIVACION DEL EJE INTESTINO-HIGADO. ESTA DESCRITO QUE LA MICROBIOTA INTESTINAL ACTUA COMO UN FACTOR CLAVE EN EL DESARROLLO DE OBESIDAD, SINDROME METABOLICO Y NAFLD, CONTRIBUYENDO A LA APARICION DE DISTINTOS FENOTIPOS DE LA ENFERMEDAD, LO QUE APOYA LA UTILIDAD DE SU MODULACION MEDIANTE AGENTES PREBIOTICOS, PROBIOTICOS Y EL TRASPLANTE DE MICROBIOTA INTESTINAL, ASI COMO MEDIANTE INTERVENCIONES NUTRICIONALES Y PROTOCOLOS DE ACTIVIDAD FISICA EN EL TRATAMIENTO DE NAFLD. ASI, LA MODULACION DE LA MICROBIOTA INTESTINAL POR EL EJERCICIO FISICO PODRIA DESEMPEÑAR UN PAPEL CLAVE EN SU EFECTO BENEFICIOSO FRENTE AL DESARROLLO DE NAFLD ASOCIADA A OBESIDAD. ADEMAS, SE HA SUGERIDO LA CAPACIDAD DEL FLAVONOIDE QUERCETINA DE MODULAR LA MICROBIOTA Y LA HOMEOSTASIS INTESTINAL. DE HECHO, NUESTRO EQUIPO DE INVESTIGACION HA DEMOSTRADO QUE LA QUERCETINA EJERCE UN PAPEL PROTECTOR FRENTE A NAFLD GRACIAS A SU ACTUACION COMO AGENTE ANTIOXIDANTE, ANTIINFLAMATORIO Y PREBIOTICO, BLOQUEANDO LA DISBIOSIS Y LA ALTERACION DEL EJE INTESTINO-HIGADO EN UN MODELO DE NAFLD (DIETA RICA EN GRASA, HFD). ASIMISMO, SE HA PROPUESTO LA UTILIDAD DEL TRASPLANTE DE MICROBIOTA INTESTINAL EN EL TRATAMIENTO DE NAFLD. EN NUESTRO RECIENTE ESTUDIO, LA HFD SE ASOCIO A LA APARICION DE FENOTIPOS METABOLICOS DISTINTOS, PERMITIENDO LA SELECCION DE DONANTES RESPONDEDOR (DHFD+) Y NO RESPONDEDOR (DHFD-) A DICHA DIETA Y EN RESPUESTA A QUERCETINA (DHFDQ), CUYA MICROBIOTA INTESTINAL SE TRASPLANTO A RATONES LIBRES DE GERMENES SOMETIDOS A HFD. LOS RESULTADOS OBTENIDOS INDICAN LA TRANSFERENCIA DE FENOTIPOS METABOLICOS PROTECTORES (DHFD- Y DHFDQ) Y PREDISPONENTE (DHFD+) A NAFLD. ADEMAS, LA DISTINTA FUNCIONALIDAD OBSERVADA EN LOS RATONES TRASPLANTADOS SE ASOCIO A PERFILES DE MICROBIOTA DEFINIDOS, DESTACANDO LA PRESENCIA O AUSENCIA DEL GENERO AKKERMANSIA. POR ELLO, EL OBJETIVO GLOBAL DEL PROYECTO CONSISTE EN EL ESTUDIO DEL EFECTO DE LA MODULACION DE LA MICROBIOTA INTESTINAL POR EL EJERCICIO FISICO COMBINADO O NO CON QUERCETINA Y SU CORRELACION CON EL FENOTIPO METABOLICO EN RATONES SOMETIDOS A HFD COMO MODELO DE NAFLD. ADEMAS, SE EVALUARA EL EFECTO DE LA TRANSFERENCIA DE FENOTIPOS METABOLICOS CON FUNCIONALIDAD PROTECTORA O PREDISPONENTE A LA ENFERMEDAD MEDIANTE EL TRASPLANTE DE MICROBIOTA INTESTINAL CARACTERIZADA A RATONES LIBRES DE GERMENES SOMETIDOS A HFD, ESTABLECIENDO EL PAPEL DE AKKERMANSIA MUCINIPHILA EN EL FENOTIPO METABOLICO DERIVADO DE LA MICROBIOTA TRASPLANTADA. EN AMBOS MODELOS IN VIVO Y EN UN MODELO IN VITRO DE INTERACCION INTESTINO-HIGADO SE PROFUNDIZARA EN EL EFECTO INDIVIDUAL Y DE LA COMBINACION DE LOS DISTINTOS MODULADORES DE LA MICROBIOTA INTESTINAL EN ASPECTOS DE LA PATOGENESIS DE LA ENFERMEDAD COMO LA ACTIVACION DEL EJE INTESTINO-HIGADO ASOCIADA A DISBIOSIS Y ALTERACION DE LA BARRERA INTESTINAL Y LA DESREGULACION DEL METABOLISMO LIPIDICO, DE LOS ACIDOS BILIARES Y DE LA VIA DE SEÑALIZACION DE LA VITAMINA D EN NUESTROS MODELOS DE NAFLD ASOCIADA A OBESIDAD. LA CONSECUCION DE DICHOS OBJETIVOS PODRIA SUPONER UN PLANTEAMIENTO INNOVADOR TANTO EN LA PREVENCION COMO EN EL TRATAMIENTO DE NAFLD ASOCIADA A OBESIDAD, AL REDUCIR LA DISBIOSIS INTESTINAL INVOLUCRADA EN EL DESARROLLO DE LA ENFERMEDAD. (Spanish)
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NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS ASSOCIATED WITH OBESITY AND REPRESENTS THE LEADING CAUSE OF CHRONIC LIVER DISEASE IN THE WESTERN COUNTRIES, INCLUDING SPAIN. INTESTINAL MICROBIOTA IMBALANCE, CHRONIC ENDOTOXEMIA AND RELATED GUT-LIVER AXIS ACTIVATION HAVE BEEN IDENTIFIED AS KEY MECHANISMS IN OBESITY-ASSOCIATED NAFLD DEVELOPMENT. THERAPEUTIC APPROACHES FOR NAFLD DEVELOPMENT AND PROGRESSION VIA MODULATION OF THE GUT MICROBIOTA HAVE BEEN PROPOSED, INCLUDING PREBIOTICS, PROBIOTICS AND GUT MICROBIOTA TRANSPLANTATION, AS WELL AS NUTRITIONAL AND PHYSICAL EXERCISE INTERVENTIONS. THUS, THE MECHANISMS BY WHICH PHYSICAL ACTIVITY PLAYS ITS PROTECTIVE ACTION IN THE DEVELOPMENT OF OBESITY AND NAFLD SEEM TO INVOLVE THE MODULATION OF GUT MICROBIOTA. MOREOVER, IT HAS ALSO BEEN INDICATED THAT NATURAL COMPOUNDS AS QUERCETIN MAY HAVE THE ABILITY TO MODIFY THE GUT MICROBIAL BALANCE, SUGGESTING A PREBIOTIC-LIKE EFFECT. IN THIS RESPECT, WE RECENTLY DEMONSTRATED THAT QUERCETIN EXERTS ITS PROTECTIVE EFFECT ON HIGH-FAT DIET (HFD)-INDUCED NAFLD IN MICE BY MEANS OF INTEGRATIVE RESPONSES INVOLVING ITS ANTIOXIDANT, ANTI-INFLAMMATORY AND PREBIOTIC CAPACITIES, MODULATING INTESTINAL MICROBIOTA IMBALANCE AND RELATED GUT-LIVER AXIS ACTIVATION, REINFORCING THE ROLE OF THIS FLAVONOL AS A POTENTIAL THERAPEUTIC STRATEGY FOR PREVENTING NAFLD DEVELOPMENT AND PROGRESSION. IT HAS ALSO BEEN PROPOSED THE ROLE OF PHENOTYPE TRANSFER BY INTESTINAL MICROBIOTA TRANSPLANTATION ON NAFLD DEVELOPMENT. IN THIS RESPECT, WE SELECTED DONORS FROM A PREVIOUS STUDY CARRIED OUT IN GERM-FREE MICE COLONIZED WITH GUT MICROBIOTA FROM DONORS (DHFD- AND DHFD+, AS NON-RESPONDER AND RESPONDER TO HFD, RESPECTIVELY, AND HFD SUPPLEMENTED WITH QUERCETIN (DHFDQ)) AND FED WITH HFD. WE OBSERVED A DIFFERENT MICROBIAL COMPOSITION IN DHFD- AND DHFDQ-RECEIVER GROUPS ASSOCIATED WITH THE TRANSFER OF A COMPLEX METABOLIC PROTECTOR PHENOTYPE WITH SPECIFIC FUNCTIONALITY IN THE RECIPIENTS. ON THE CONTRARY, DHFD+-RECEIVERS REVEALED A PHYLOTYPE PREDISPOSED TO DEVELOP NAFLD ASSOCIATED WITH THE TRANSFER OF A PARTICULAR INTESTINAL MICROBIOTA, HIGHLIGHTING THE KEY ROLE OF AKKERMANSIA GENUS ON THE PROTECTIVE METABOLIC PHENOTYPE ASSOCIATED TO GUT MICROBIOTA TRANSFER. THIS RESEARCH IS AIMED TO INVESTIGATE BENEFITS OF MODULATION OF OBESITY-RELATED NAFLD BY PHYSICAL EXERCISE AND QUERCETIN AND METABOLIC PHENOTYPE TRANSFER THROUGH INTESTINAL MICROBIOTA TRANSPLANTATION FROM DONORS WITH ESTABLISHED GUT MICROBIOTA AND METABOLOMIC PROFILES RELATED TO A PROTECTIVE OR PREDISPOSING FUNCTIONAL PHENOTYPE TRANSFER WITH OR WITHOUT AKKERMANSIA MUCINIPHILA COLONIZATION IN HFD TREATED GEREM-FREE MICE. THE MECHANISMS BY WHICH PHYSICAL ACTIVITY AND QUERCETIN, AND GUT MICROBIOTA AND AKKERMANSIA MUCINIPHILA TRANSPLANTATION PLAY THEIR PROTECTIVE ACTION IN THE DEVELOPMENT OF NAFLD WILL ALSO BE STUDIED, FOCUSING PRIMARILY ON THE MODULATION OF GUT MICROBIOTA AND THE ACTIVATION OF GUT-LIVER AXIS ASSOCIATED TO ENDOTOXEMIA-DERIVED DYSBIOSIS, OXIDATIVE STRESS, INFLAMMATION AND BILE ACID AND LIPID METABOLISM DEREGULATION AND VITAMIN D RECEPTOR-RELATED PATHWAY ALTERATION IN OUR IN VITRO AND IN VIVO MODELS OF NAFLD. ACHIEVEMENT OF THE PROPOSED OBJECTIVES WOULD PROVIDE SCIENTIFIC SUPPORT FOR THE USE OF PROTOCOLS OF PHYSICAL EXERCISE AND THE PREBIOTIC QUERCETIN AS MODULATORS OF THE INTESTINAL MICROBIOTA AND THE TRANSFER OF COMPLEX METABOLIC PHENOTYPES THROUGH GUT MICROBIOTA TRANSPLANTATION IN THE MANAGEMENT OF OBESITY-RELATED NAFLD. (English)
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León
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Identifiers
BFU2017-87960-R
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