An Exploratory Study on the Pathogenic Role of Faecal Extracellular Vesicles in Metabolic Dysfunction-Associated Steatotic Liver Disease Progression and in Drug-Induced Liver Injury. - 2026
An Exploratory Study on the Pathogenic Role of Faecal Extracellular Vesicles in Metabolic Dysfunction-Associated Steatotic Liver Disease Progression and in Drug-Induced Liver Injury.
Ruiz-Malagón, Antonio J; Herraiz-Vilela, Marina; Pinazo-Bandera, Joseet al.
2026 • In Journal of Extracellular Vesicles, 15 (3), p. 70240
MASLD; faecal extracellular vesicles; idiosyncratic drug‐induced liver injury; Humans; Gastrointestinal Microbiome; Male; Female; Hep G2 Cells; Middle Aged; Disease Progression; Aged; Adult; Extracellular Vesicles/metabolism; Feces/microbiology; Chemical and Drug Induced Liver Injury/metabolism; Chemical and Drug Induced Liver Injury/microbiology; Chemical and Drug Induced Liver Injury/pathology; Fatty Liver/metabolism; Fatty Liver/microbiology; Fatty Liver/pathology
Abstract :
[en] The role of extracellular vesicles secreted by the gut microbiota present in faeces (fEVs) is not well known in metabolic dysfunction-associated steatotic liver disease (MASLD) and idiosyncratic drug-induced liver injury (DILI). We identify the microbiome profiles of fEVs in these liver diseases, and analyse the effects of fEVs from MASLD, without (F≤2) or with (F≥3) significant liver fibrosis, and DILI patients on inflammation, steatosis and mitochondrial function. DILI patients showed a consistent pattern in fEVs, characterised by a decrease in Paraprevotella and an increase in AAP99, Acinetobacter, Actinobacillus, Aerococcus and Anaeroglobus. A higher presence of 16S rDNA was observed in plasma EVs from MASLD and DILI patients. HepG2 cells treated with DILI and MASLD F≥3 fEVs increased TLR4, TLR5, IL6 and CASP3 expression, and accumulation of lipid droplets. DILI fEVs enhanced the hepatotoxic impact of diclofenac on the response to microbial components (TLR4, TLR5), inflammatory response (IL1B, IL6), accumulation of lipid droplets and mitochondrial dysfunction (OPA1, DNM1L). In conclusion, bacterial EVs enter the bloodstream and could modulate the immune response. DILI and MASLD F≥3 fEVs are drivers of the pro-inflammatory response and hepatocyte steatosis. DILI fEVs have a distinct bacterial profile that enhances the hepatotoxic potential of diclofenac.
Research Center/Unit :
FARAH. Santé publique vétérinaire - ULiège
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Ruiz-Malagón, Antonio J; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
Herraiz-Vilela, Marina; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
Pinazo-Bandera, Jose; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain
Toro-Ortiz, Juan Pedro; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
López-Gómez, Carlos; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain
Ho-Plagaro, Ailec; Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA), Granada, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de las Nieves, Granada, Spain
Garrido-Sánchez, Lourdes; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Málaga, Spain
Robles-Díaz, Mercedes; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain ; Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
Taminiau, Bernard ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Microbiologie des denrées alimentaires
Daube, Georges ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Microbiologie des denrées alimentaires
Sanabria-Cabrera, Judith; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Servicio de Farmacologia Clinica, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
Matilla-Cabello, Gonzalo; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
Lucena, Maria Isabel; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain ; Servicio de Farmacologia Clinica, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, Málaga, Spain ; UICEC IBIMA, Plataforma de Investigación Clínica del ISCIII (SCReN, Spanish Clinical Research Network), Málaga, Spain
Andrade, Raúl J; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain ; Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, Málaga, Spain
García-Fuentes, Eduardo ; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain
García-Cortes, Miren; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd), Málaga, Spain
Rodriguez-Diaz, Cristina; IBIMA Plataforma BIONAND, Instituto de Investigación Biomédica de Málaga, Málaga, Spain ; Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Málaga, Spain
An Exploratory Study on the Pathogenic Role of Faecal Extracellular Vesicles in Metabolic Dysfunction-Associated Steatotic Liver Disease Progression and in Drug-Induced Liver Injury.
EU - European Union ISCIII - Instituto de Salud Carlos III Instituto de Salud Carlos III Junta de Andalucía Junta de Andalucía. Consejería de Economía, Conocimiento, Empresas y Universidad
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