Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma BIONAND, 29590 Málaga, Spain; UGC de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain.
Fundamental and Applied Research for Animals & Health (FARAH), Department of Food Microbiology, Faculty of Veterinary Medicine, University of Liège, 4000 Liège, Belgium.
Pharmacol Res. 2022 Aug;182:106348. doi: 10.1016/j.phrs.2022.106348. Epub 2022 Jul 8.
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.
肠道微生物群可能在非酒精性脂肪性肝病 (NAFLD) 的进展中发挥重要作用；然而，其在药物性肝损伤 (DILI) 中的相关性仍未得到探索。由于这两种肝部疾病可能具有共同的损伤途径，我们分析了伴有或不伴有显著肝纤维化的 NAFLD 以及 DILI 患者的肠道微生物群的宏基因组图谱，并确定了主要相关的细菌代谢途径。在 NAFLD 组中，与 DILI 组和对照组相比，我们发现 Alistipes、Barnesiella、Eisenbergiella、Flavonifractor、Fusicatenibacter、Gemminger、Intestinimonas、Oscillibacter、Parasutterella、Saccharoferementans 和 Subdoligranulum 的丰度降低。此外，我们还发现，与无/轻度肝纤维化的 NAFLD 患者相比，伴有显著肝纤维化的 NAFLD 患者的 Enterobacter、Klebsiella、Sarcina 和 Turicibacter 的丰度增加。与对照组相比，DILI 组的微生物细菌丰富度较低，与 NAFLD 组和对照组相比，Acetobacteroides、Blautia、Caloramator、Coprococcus、Flavobacterium、Lachnospira、Natronincola、Oscillospira、Pseudobutyrivibrio、Shuttleworthia、Themicanus 和 Turicibacter 的丰度较低。我们发现了七个仅在 DILI 中受损的细菌代谢途径，其中大多数与代谢生物合成有关。在 NAFLD 组中，与 DILI 组和对照组相比，大多数与细菌代谢途径相关的差异与脂肪酸和脂质生物合成有关。总之，我们确定了每种类型的肝部疾病所特有的不同的细菌图谱和特定的细菌代谢途径。这些差异可以为 NAFLD 和 DILI 的病理生理学和发展提供进一步的见解。
