益气补肾调脂方对高脂高果糖饮食诱导的非酒精性脂肪性肝炎小鼠肠道菌群的影响。
Yiqi-Bushen-Tiaozhi Recipe Attenuated High-Fat and High-Fructose Diet Induced Nonalcoholic Steatohepatitis in Mice Gut Microbiota.
机构信息
The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
The Second Central Laboratory, Key Lab of Integrative Chinese and Western Medicine for the Diagnosis and Treatment of Circulatory Diseases of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
出版信息
Front Cell Infect Microbiol. 2022 Apr 22;12:824597. doi: 10.3389/fcimb.2022.824597. eCollection 2022.
AIM
To investigate the treating effect of Yiqi-Bushen-Tiaozhi (YBT) recipe on nonalcoholic steatohepatitis (NASH) mice, determine whether the outcome was associated with gut microbiota, and clarify the regulating mechanism.
METHODS
NASH mice were induced by high-fat and high-fructose diets (HFFD). In the fifth week, mice in the YBT group were orally administrated YBT (22.12g·kg·d) daily for 12 weeks. Fresh stool of mice was collected at the 16 week for fecal 16S rDNA analysis. Hepatic pathology and biochemical indicators were used to reflect the improvement of YBT on hepatic inflammation and lipid metabolism in NASH mice. Quantitative real-time PCR (qRT-PCR) was used to verify the results of PICRUSt analysis.
RESULTS
Results of the pathological and biochemical index showed that YBT could improve NASH mice. Compared with improving inflammation and hepatocyte damage, YBT may be more focused on enhancing metabolic disorders in mice, such as increasing HDL-c level. The diversity and richness of the gut microbiota of NASH mice induced by HFFD are significantly different from the normal control (NC) group. After YBT treatment, the diversity and richness of the mice microbiota will be increased to similar NC mice. , and have the most significant changes in the class level. PICRUSt analysis was performed to predict genomic functions based on the 16S rDNA results and reference sequencing. The efficacy of YBT in the treatment of NASH can be achieved by regulating the diversity and richness of gut microbiota. PICRUSt analysis results showed that the most relevant function of the microbiota construction variations is α- Linolenic acid (ALA) metabolism. Results of qRT-PCR showed significant differences between groups in the expression of Fatty acid desaturase 1 (FADS1), Fatty acid desaturase 2 (FADS2), Acyl-CoA Oxidase 1 (ACOX1), and Acyl-CoA Oxidase 2 (ACOX2) related to ALA metabolism. The expression of the above genes will be inhibited in the liver and small intestine of the HFFD group mice, and the expression can be restored after YBT treatment.
CONCLUSION
YBT could treat NASH mice by improving the diversity and richness of gut microbiota and further the improvement of ALA metabolism.
目的
探讨益气补肾调脂方（YBT）对非酒精性脂肪性肝炎（NASH）小鼠的治疗作用，确定其疗效是否与肠道微生物群相关，并阐明其调控机制。
方法
采用高脂高果糖饲料（HFFD）诱导 NASH 小鼠。在第 5 周，YBT 组小鼠每天口服 YBT（22.12g·kg·d），共 12 周。第 16 周时收集新鲜粪便，进行粪便 16S rDNA 分析。肝组织病理学和生化指标用于反映 YBT 对 NASH 小鼠肝炎症和脂质代谢的改善作用。采用实时荧光定量 PCR（qRT-PCR）验证 PICRUSt 分析结果。
结果
病理生化指标结果表明，YBT 可改善 NASH 小鼠。与改善炎症和肝细胞损伤相比，YBT 可能更侧重于增强小鼠的代谢紊乱，如增加高密度脂蛋白胆固醇（HDL-c）水平。HFFD 诱导的 NASH 小鼠的肠道微生物多样性和丰富度与正常对照组（NC）显著不同。YBT 治疗后，小鼠的微生物多样性和丰富度增加，与 NC 小鼠相似。在属水平上， 和 变化最显著。基于 16S rDNA 结果和参考测序进行 PICRUSt 分析以预测基因组功能。YBT 治疗 NASH 的疗效可通过调节肠道微生物多样性来实现。PICRUSt 分析结果表明，微生物结构变化最相关的功能是α-亚麻酸（ALA）代谢。qRT-PCR 结果显示，ALA 代谢相关的脂肪酸去饱和酶 1（FADS1）、脂肪酸去饱和酶 2（FADS2）、酰基辅酶 A 氧化酶 1（ACOX1）和酰基辅酶 A 氧化酶 2（ACOX2）在各组间的表达存在显著差异。HFFD 组小鼠的肝脏和小肠中上述基因的表达受到抑制，YBT 治疗后可恢复表达。
结论
YBT 可通过改善肠道微生物多样性和进一步改善 ALA 代谢来治疗 NASH 小鼠。
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