RT Journal Article
T1 Membrane vesicles of toxigenic Clostridioides difficile affect the metabolism of liver hepG2 cells
A1 Caballano-Infantes, Estefanía
A1 Ho-Plágaro, Ailec
A1 López-Gómez, Carlos
A1 Martín-Reyes, Flores
A1 Rodríguez-Pacheco, Francisca
A1 Taminiau, Bernard
A1 Daube, Georges
A1 Garrido Sánchez, Lourdes
A1 Alcaín-Martínez, Guillermo
A1 Andrade-Bellido, Raúl Jesús
A1 García-Cortés, Miren
A1 Lucena-González, María Isabel
A1 García Fuentes, Eduardo
A1 Rodriguez-Diaz, Cristina
K1 Células hepáticas
K1 Metabolismo
K1 Vesícula biliar
K1 Aparato digestivo-Enfermedades
K1 Patógenos
K1 Patología celular
AB 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.
PB MDPI
YR 2023
FD 2023-03-27
LK https://hdl.handle.net/10630/26958
UL https://hdl.handle.net/10630/26958
LA eng
NO Caballano-Infantes E, Ho-Plágaro A, López-Gómez C, Martín-Reyes F, Rodríguez-Pacheco F, Taminiau B, Daube G, Garrido-Sánchez L, Alcaín-Martínez G, Andrade RJ, et al. Membrane Vesicles of Toxigenic Clostridioides difficile Affect the Metabolism of Liver HepG2 Cells. Antioxidants. 2023; 12(4):818. https://doi.org/10.3390/antiox12040818
NO Partial funding for open access charge: Universidad de Málaga
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026