Drug induced liver injury, non-alcoholic fatty liver disease; gut microbiota; liver fibrosis; metabolic pathways; metagenomic; Pharmacology
Abstract :
[en] The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liver fibrosis, and in DILI, and we identified the main associated bacterial metabolic pathways. In the NAFLD group, we found a decrease in Alistipes, Barnesiella, Eisenbergiella, Flavonifractor, Fusicatenibacter, Gemminger, Intestinimonas, Oscillibacter, Parasutterella, Saccharoferementans and Subdoligranulum abundances compared with those in both the DILI and control groups. Additionally, we detected an increase in Enterobacter, Klebsiella, Sarcina and Turicibacter abundances in NAFLD, with significant liver fibrosis, compared with those in NAFLD with no/mild liver fibrosis. The DILI group exhibited a lower microbial bacterial richness than the control group, and lower abundances of Acetobacteroides, Blautia, Caloramator, Coprococcus, Flavobacterium, Lachnospira, Natronincola, Oscillospira, Pseudobutyrivibrio, Shuttleworthia, Themicanus and Turicibacter compared with those in the NAFLD and control groups. We found seven bacterial metabolic pathways that were impaired only in DILI, most of which were associated with metabolic biosynthesis. In the NAFLD group, most of the differences in the bacterial metabolic pathways found in relation to those in the DILI and control groups were related to fatty acid and lipid biosynthesis. In conclusion, we identified a distinct bacterial profile with specific bacterial metabolic pathways for each type of liver disorder studied. These differences can provide further insight into the physiopathology and development of NAFLD and DILI.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
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
Taminiau, Bernard ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
García-García, Alberto; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain
Cueto, Alejandro; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain, Servicio de Farmacologia Clinica, Hospital Universitario Virgen de la Victoria, Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain
Robles-Díaz, Mercedes; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain, Departamento de Medicina, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 29010 Málaga, Spain
Ortega-Alonso, Aida; 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
Daube, Georges ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Sanabria-Cabrera, Judith; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain, Servicio de Farmacologia Clinica, 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
Jimenez-Perez, Miguel; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain, UGC de Enfermedades Digestivas, Hospital Regional Universitario, 29010 Málaga, Spain
Isabel Lucena, M; Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29010 Málaga, Spain, Servicio de Farmacologia Clinica, Hospital Universitario Virgen de la Victoria, Departamento de Farmacología, Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 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. Electronic address: lucena@uma.es
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, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 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, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 29010 Málaga, Spain. Electronic address: edugf1@gmail.com
García-Cortes, 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, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 29010 Málaga, Spain
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