[en] Clostridioides difficile infection (CDI) appears to be associated with different liver diseases. C. difficile secretes membrane vesicles (MVs), which may be involved in the development of nonalcoholic fatty liver disease (NALFD) and drug-induced liver injury (DILI). In this study, we investigated the presence of C. difficile-derived MVs in patients with and without CDI, and analyzed their effects on pathways related to NAFLD and DILI in HepG2 cells. Fecal extracellular vesicles from CDI patients showed an increase of Clostridioides MVs. C. difficile-derived MVs that were internalized by HepG2 cells. Toxigenic C. difficile-derived MVs decreased mitochondrial membrane potential and increased intracellular ROS compared to non-toxigenic C. difficile-derived MVs. In addition, toxigenic C. difficile-derived MVs upregulated the expression of genes related to mitochondrial fission (FIS1 and DRP1), antioxidant status (GPX1), apoptosis (CASP3), glycolysis (HK2, PDK1, LDHA and PKM2) and β-oxidation (CPT1A), as well as anti- and pro-inflammatory genes (IL-6 and IL-10). However, non-toxigenic C. difficile-derived MVs did not produce changes in the expression of these genes, except for CPT1A, which was also increased. In conclusion, the metabolic and mitochondrial changes produced by MVs obtained from toxigenic C. difficile present in CDI feces are common pathophysiological features observed in the NAFLD spectrum and DILI.
Research center :
FARAH. Santé publique vétérinaire - ULiège
Disciplines :
Immunology & infectious disease
Author, co-author :
Caballano-Infantes, Estefanía ; Department of Regeneration and Cell Therapy Andalusian, Center for Molecular Biology and Regenerative Medicine (CABIMER), University of Pablo de Olavide-University of Seville-CSIC, Junta de Andalucía, 41092 Seville, Spain
Ho-Plágaro, Ailec; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
López-Gómez, Carlos ; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
Martín-Reyes, Flores ; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
Rodríguez-Pacheco, Francisca; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
Taminiau, Bernard ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Daube, Georges ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Microbiologie des denrées alimentaires
Garrido-Sánchez, Lourdes; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain ; CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28029 Madrid, Spain
Alcaín-Martínez, Guillermo; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
Andrade, Raúl J. ; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain ; Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain
García-Cortés, Miren; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain ; Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain
Lucena, M. Isabel ; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain ; Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain ; UICEC IBIMA, Plataforma SCReN (Spanish Clinical Research Network), Servicio de Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, 29010 Málaga, Spain
García-Fuentes, Eduardo ; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain ; CIBER de Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, 28029 Madrid, Spain
Rodriguez Diaz, Cristina ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) ; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina, IBIMA Plataforma BIONAND, 29010 Málaga, Spain ; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
ISCIII - Instituto de Salud Carlos III [ES] FEDER - Fonds Européen de Développement Régional [BE] Junta de Andalucía. Consejería de Economía, Conocimiento, Empresas y Universidad [ES]
Funding text :
FEDER funds (“A way to make Europe”); Nicolas Monardes program from the Consejería de Salud de Andalucía
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