Comprehensive Analysis of Fecal Microbiome and Metabolomics in Hepatic Fibrosis Rats Reveal Hepatoprotective Effects of Yinchen Wuling Powder From the Host-Microbial Metabolic Axis.

Comprehensive Analysis of Fecal Microbiome and Metabolomics in Hepatic Fibrosis Rats Reveal Hepatoprotective Effects of Yinchen Wuling Powder From the Host-Microbial Metabolic Axis.
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DOI:
10.3389/fphar.2021.713197
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发表时间:
2021
影响因子:
5.6
通讯作者:
Wang M
Wang M
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Y;Zhao M;Jiang X;Qiao Q;Liu T;Zhao C;Wang M

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肝纤维化(hepatic fibrosis,HF)是多种慢性肝病发展的典型结果,与肠道菌群组成和代谢状态密切相关。大量证据表明,中药可以通过调节肠道微生物群来治疗HF。茵陈五苓散是一个著名的传统中药方剂,几千年来一直被用来缓解肝病。YCWLP对HF具有保护作用,但其对肠道菌群改变的影响尚不清楚,其明确的治疗机制也需要进一步阐明。本研究采用16S rRNA基因测序和粪便代谢组学分析相结合的方法,探讨YCWLP对HF大鼠肠道菌群的影响以及肠道菌群与宿主代谢的相互作用。结果表明,益气活血颗粒能明显改善HF所致的多脏器指数、HF相关细胞因子及血浆内毒素水平的紊乱。Masson三色染色结果也显示YCWLP治疗能显著减轻大鼠心衰的严重程度。此外,YCWLP可以逆转与HF表型密切相关的某些属的丰度的显著变化,包括Barnesiella [Ruminococcus]和Christensenella。同时,YCWLP显著增加了与丁酸产生密切相关的双歧杆菌、粪球菌和厌氧杆菌的丰度。代谢组学和斯皮尔曼相关分析表明,YCWLP对HF大鼠精氨酸生物合成、鞘脂代谢、丙氨酸、天冬氨酸和谷氨酸代谢紊乱具有调节作用,且这种调节作用与Barnesiella、[Ruminococcus]、Christensenella、Coprococcus和Anaerostipes密切相关。通过解释上述结果的生物学意义,我们得出结论,YCWLP可能通过调节肠道微生物群的失衡,增加产丁酸菌的丰度以减少氨的产生,促进氨的降解,以及调节促炎细胞因子和免疫功能来改善HF。
Hepatic fibrosis (HF) is a typical consequence in the development of multiple chronic liver diseases, which is intimately related to the composition and metabolic status of gut microbiota. A myriad of evidence has indicated that traditional Chinese medicine can treat HF by regulating gut microbiota. Yinchen Wuling powder (YCWLP) is a famous traditional Chinese medicine prescription, which has been used to relieve liver diseases for thousands of years. YCWLP has demonstrated protective function on HF, but its effect on the alterations of gut microbiota is still unclear, and its explicit therapeutic mechanism also needs to be further elucidated. In this study, 16S rRNA gene sequencing and fecal metabolomics analysis were combined to investigate the influence of YCWLP on gut microbiota in HF rats and the interactions between gut microbiota and host metabolism. The results showed that YCWLP treatment significantly improved the disorder of multiple organ indices, HF-related cytokines and plasma LPS induced by HF. Masson’s trichrome stainings also showed that YCWLP treatment could significantly alleviate the severity of HF in rats. Additionally, YCWLP could reverse the significant changes in the abundance of certain genera closely related to HF phenotype, including Barnesiella [Ruminococcus] and Christensenella. Meanwhile, YCWLP significantly increased the abundance of Bifidobacterium, Coprococcus and Anaerostipes, which are closely related to butyrate production. Metabolomics and Spearman’s correlation analysis showed that YCWLP could regulate the disorder of arginine biosynthesis, sphingolipid metabolism and alanine, aspartate and glutamate metabolism in HF rats, and these regulations were intimately related to Barnesiella, [Ruminococcus], Christensenella, Coprococcus and Anaerostipes. By explaining the biological significance of the above results, we concluded that YCWLP might ameliorate HF by regulating the imbalance of gut microbiota, increasing the abundance of butyrate-producing bacteria to reduce ammonia production, promote ammonia degradation, and regulate pro-inflammatory cytokines and immune function.
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