2024-03-28T23:58:33Zhttp://buleria.unileon.es/oai/requestoai:buleria.unileon.es:10612/153202023-01-17T10:58:03Zcom_10612_17col_10612_18
Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression
Juárez‐Fernández, María
Goikoetxea‐Usandizaga, Naroa
Porras, David
García Mediavilla, María Victoria
Bravo, Miren
Serrano‐Maciá, Marina
Simón, Jorge
Delgado, Teresa C.
Lachiondo‐Ortega, Sofía
Martínez‐Flórez, Susana
Lorenzo, Óscar
Rincón, Mercedes
Varela‐Rey, Marta
Abecia, Leticia
Rodríguez, Héctor
Anguita, Juan
Nistal González, Maria Esther
Martínez‐Chantar, María Luz
Sánchez Campos, Sonia
Fisiologia
Fisiología
[EN] Background and Aims: Recent studies suggest that mitochondrial dysfunction promotes progression to NASH by aggravating the gut-liver status. However, the underlying mechanism remains unclear. Herein, we hypothesized that enhanced mitochondrial activity might reshape a specific microbiota signature that, when transferred to germ-free (GF) mice, could delay NASH progression. Approach and Results: Wild-type and methylation-controlled J protein knockout (MCJ-KO) mice were fed for 6 weeks with either control or a choline-deficient, L-amino acid–defined, high-fat diet (CDA-HFD). One mouse of each group acted as a donor of cecal microbiota to GF mice, who also underwent the CDA-HFD model for 3 weeks. Hepatic injury, intestinal barrier, gut microbiome, and the associated fecal metabolome were then studied. Following 6 weeks of CDA-HFD, the absence of methylation-controlled J protein, an inhibitor of mitochondrial complex I activity, reduced hepatic injury and improved gut-liver axis in an aggressive NASH dietary model. This effect was transferred to GF mice through cecal microbiota transplantation. We suggest that the specific microbiota profile of MCJ-KO, characterized by an increase in the fecal relative abundance of Dorea and Oscillospira genera and a reduction in AF12, Allboaculum, and [Ruminococcus], exerted protective actions through enhancing short-chain fatty acids, nicotinamide adenine dinucleotide (NAD+) metabolism, and sirtuin activity, subsequently increasing fatty acid oxidation in GF mice. Importantly, we identified Dorea genus as one of the main modulators of this microbiota-dependent protective phenotype. Conclusions: Overall, we provide evidence for the relevance of mitochondria–microbiota interplay during NASH and that targeting it could be a valuable therapeutic approach.
2022-12-12
2022-12-12
info:eu-repo/semantics/article
Juárez-Fernández, M., Goikoetxea-Usandizaga, N., Porras, D., García-Mediavilla, M. V., Bravo, M., Serrano-Maciá, M., Simón, J., Delgado, T. C., Lachiondo-Ortega, S., Martínez-Flórez, S., Lorenzo, Ó., Rincón, M., Varela-Rey, M., Abecia, L., Rodríguez, H., Anguita, J., Nistal, E., Martínez-Chantar, M. L., & Sánchez-Campos, S. (2022). Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression. Hepatology. https://doi.org/10.1002/HEP.32705
0270-9139
http://hdl.handle.net/10612/15320
10.1002/hep.32705
1527-3350
info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/BFU2017- 87960- R/ES/EFECTO DEL EJERCICIO FISICO Y QUERCETINA Y DEL TRASPLANTE DE MICROBIOTA INTESTINAL PROTECTORA O PREDISPONENTE ADICIONADA CON AKKERMANSIA MUCINIPHILA EN MODELOS DE NAFLD
info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/PID2020- 120363RB- I/ES/MICROBIOTA INTESTINAL Y DAÑO HEPATICO POR FARMACOS (DILI). TRANSFERENCIA DE PERFILES ESPECIFICOS Y MODULACION DE MICROBIOTA EN MODELOS EXPERIMENTALES DE DILI POR CLAVULANATO
info:eu-repo/grantAgreement/AEI/Programa Estatal de I+D+i Orientada a los Retos de la Sociedad/PID2020-117116RB-I00/ES/DESVELANDO EL PAPEL DE LA NEDILACION EN EL ESTRES NUTRICIONAL
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Wiley-Blackwell