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Título
Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression
Autor
Facultad/Centro
Área de conocimiento
Título de la revista
Hepatology
Datos de la obra
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
Editor
Wiley-Blackwell
Fecha
2022
ISSN
0270-9139
Zusammenfassung
[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.
Materia
Palabras clave
Peer review
SI
ID proyecto
- 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
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