biostudies-literatureJuarez-Fernandez MJunta de Castilla y León cofunded by the European Social FundDepartamento de Industria del Gobierno VascoAyudas Ramón y Cajal de la Agencia Estatal de InvestigaciónMinisterio de Ciencia, Innovación y Universidades MICINN integrado en el Plan Estatal de Investigación Científica y Técnica y de Innovación, cofinanciado con Fondos FEDERJunta de Castilla y LeónMinisterio de Economía y Competitividad/FEDERProyecto Desarrollo Tecnologico CIBERehdBIOEF (Basque Foundation for Innovation and Health Research)Instituto de Salud Carlos III, Proyectos de Investigación en SaludJunta de Castilla y León (FEDER)Ministerio de Ciencia e Innovación, Programa Retos-ColaboraciónFundación Científica de la Asociación Española Contra el Cancer (AECC Scientific Foundation) Rare Tumor Calls 2017Ministerio de Ciencia, Innovación y UniversidadesAsociación Española contra el CáncerBerrikuntza + Ikerketa + Osasuna Eusko FundazioaMinisterio de Economía y CompetitividadLa Caixa Foundation Program1654-1669https://www.ebi.ac.uk/biostudies/studies/S-EPMC10113004biostudies-literatureUnknown77(5)<h4>Background and aims</h4>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.<h4>Approach and results</h4>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 metabolHepatology (Baltimore, Md.)Enhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.PMC10113004PID2020-120363RB-I0DTS20/00138LE063U16BFU2017-87960-RGRS2126/A/2020PID2020‐120363RB‐I0FPU18/06257LE017P20RTC2019-007125-1PID2020-117116RB-I00BFU2017‐87960‐RRY2013-13666Delgado TCRodriguez HBravo MSimon JLorenzo OGarcia-Mediavilla MVLachiondo-Ortega SSerrano-Macia MAnguita JAbecia LJuarez-Fernandez MRincon MMartinez-Chantar MLSanchez-Campos SMartinez-Florez SGoikoetxea-Usandizaga NPorras DVarela-Rey MNistal EfalseEnhanced mitochondrial activity reshapes a gut microbiota profile that delays NASH progression.<h4>Background and aims</h4>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.<h4>Approach and results</h4>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 metabol2023-01-01T00:00:00Z2023 May2025-04-04T08:28:54.988Z2025-04-04T08:28:54.988ZS-EPMC101130043592119910.1002/hep.32705