Li Jingwei, Zhao Min, Li Jianming, Wang Miao, Zhao Chunjie
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Guangxi University of Chinese Medicine, Nanning, China.
Front Pharmacol. 2022 Aug 16;13:911356. doi: 10.3389/fphar.2022.911356. eCollection 2022.
Chemical liver injury is closely related to gut microbiota and its metabolites. In this study, we combined 16S rRNA gene sequencing, H NMR-based fecal metabolomics and GC-MS to evaluate the changes in gut microbiota, fecal metabolites and Short-chain fatty acids (SCFAs) in CCl-induced liver injury in Sprague-Dawley rats, and the therapeutic effect of Shaoyao Gancao Decoction (SGD). The results showed that CCl-induced liver injury overexpressed CYP2E1, enhanced oxidative stress, decreased antioxidant enzymes (SOD, GSH), increased peroxidative products MDA and inflammatory responses (IL-6, TNF-α), which were ameliorated by SGD treatment. H&E staining showed that SGD could alleviate liver tissue lesions, which was confirmed by the recovered liver index, ALT and AST. Correlation network analysis indicated that liver injury led to a decrease in microbiota correlation, while SGD helped restore it. In addition, fecal metabolomic confirmed the PICRUSt results that liver injury caused disturbances in amino acid metabolism, which were modulated by SGD. Spearman's analysis showed that liver injury disrupted ammonia transport, urea cycle, intestinal barrier and energy metabolism. Moreover, the levels of SCFAs were also decreased, and the abundance of Lachnoclostridium, Blautia, Lachnospiraceae_NK4A136_group, UCG-005 and Turicibacter associated with SCFAs were altered. However, all this can be alleviated by SGD. More importantly, pseudo germ-free rats demonstrated that the absence of gut microbiota aggravated liver injury and affected the efficacy of SGD. Taken together, we speculate that the gut microbiota has a protective role in the pathogenesis of liver injury, and has a positive significance for the efficacy of SGD. Moreover, SGD can treat liver injury by modulating gut microbiota and its metabolites and SCFAs. This provides useful evidence for the study of the pathogenesis of liver injury and the clinical application of SGD.
化学性肝损伤与肠道微生物群及其代谢产物密切相关。在本研究中，我们结合16S rRNA基因测序、基于核磁共振氢谱的粪便代谢组学和气相色谱-质谱联用技术，评估了四氯化碳诱导的Sprague-Dawley大鼠肝损伤中肠道微生物群、粪便代谢产物和短链脂肪酸（SCFAs）的变化，以及芍药甘草汤（SGD）的治疗效果。结果显示，四氯化碳诱导的肝损伤使CYP2E1过表达，增强了氧化应激，降低了抗氧化酶（超氧化物歧化酶、谷胱甘肽），增加了过氧化产物丙二醛和炎症反应（白细胞介素-6、肿瘤坏死因子-α），而SGD治疗可改善这些情况。苏木精-伊红染色显示，SGD可减轻肝组织损伤，这通过恢复的肝脏指数、谷丙转氨酶和谷草转氨酶得到证实。相关性网络分析表明，肝损伤导致微生物群相关性降低，而SGD有助于恢复。此外，粪便代谢组学证实了PICRUSt的结果，即肝损伤导致氨基酸代谢紊乱，而SGD可对其进行调节。斯皮尔曼分析表明，肝损伤扰乱了氨转运、尿素循环、肠道屏障和能量代谢。此外，短链脂肪酸水平也降低，与短链脂肪酸相关的梭菌属、布劳特氏菌属、毛螺菌科_NK4A136_group、UCG-005和Turicibacter的丰度发生改变。然而，所有这些都可通过SGD得到缓解。更重要的是，无菌大鼠模型表明，肠道微生物群的缺失会加重肝损伤并影响SGD的疗效。综上所述，我们推测肠道微生物群在肝损伤发病机制中具有保护作用，对SGD的疗效具有积极意义。此外，SGD可通过调节肠道微生物群及其代谢产物和短链脂肪酸来治疗肝损伤。这为肝损伤发病机制的研究及SGD的临床应用提供了有用的证据。
