RT info:eu-repo/semantics/article
T1 Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression
A1 Juárez‐Fernández, María
A1 Goikoetxea‐Usandizaga, Naroa
A1 Porras, David
A1 García Mediavilla, María Victoria
A1 Bravo, Miren
A1 Serrano‐Maciá, Marina
A1 Simón, Jorge
A1 Delgado, Teresa C.
A1 Lachiondo‐Ortega, Sofía
A1 Martínez‐Flórez, Susana
A1 Lorenzo, Óscar
A1 Rincón, Mercedes
A1 Varela‐Rey, Marta
A1 Abecia, Leticia
A1 Rodríguez, Héctor
A1 Anguita, Juan
A1 Nistal González, Maria Esther
A1 Martínez‐Chantar, María Luz
A1 Sánchez Campos, Sonia
A2 Fisiologia
K1 Fisiología
K1 Mitochondrial dysfunction
K1 Nonalcoholic Steatohepatitis (NASH)
K1 2411 Fisiología Humana
AB [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.
PB Wiley-Blackwell
SN 0270-9139
LK http://hdl.handle.net/10612/15320
UL http://hdl.handle.net/10612/15320
NO 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
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 19-abr-2024