Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism.

Modulation of Gut Microbiota and Metabolites by Berberine in Treating Mice With Disturbances in Glucose and Lipid Metabolism.
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小檗碱对葡萄糖和脂质代谢紊乱小鼠的肠道微生物群和代谢物的调节

DOI:
10.3389/fphar.2022.870407
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发表时间:
2022
影响因子:
5.6
通讯作者:
Tian, Jiaxing
Tian, Jiaxing
中科院分区:
医学2区
文献类型:
--
作者:
Fang, Xinyi;Wu, Haoran;Wang, Xinmiao;Lian, Fengmei;Li, Min;Miao, Runyu;Wei, Jiahua;Tian, Jiaxing

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前言:糖脂代谢紊乱已成为继肿瘤、心脑血管疾病之后的第三大疾病。新的证据表明,小檗碱可以有效地干预糖脂代谢紊乱,但其机制尚不清楚。为了研究这个问题,我们对一组正常小鼠(NC组)、糖脂代谢紊乱小鼠(MC组)和小檗碱干预后糖脂代谢紊乱小鼠(BER组)进行了宏基因组学和代谢组学分析。结果:首先,临床指标分析显示,黄连素能显著改善宿主的血糖和血脂。8周后BER组空腹血糖水平下降约30%,口服葡萄糖耐量试验显示BER组的血糖水平在任何时间均低于MC组。此外,黄连素显着降低体重,血浆总胆固醇和甘油三酯。其次,与NC组相比,我们发现MC组和BER组的微生物丰富度和多样性显著降低。第三,LDA效应量表明,小檗碱显著改变了整体肠道微生物群结构,并富集了许多细菌,包括阿克曼氏菌(p < 0.01)、真杆菌(p < 0.01)和瘤胃球菌(p < 0.01)。第四,代谢组学分析表明,各组的代谢组学特征存在显著差异。例如,异亮氨酸(p < 0.01)、苯丙氨酸(p < 0.05)和熊果苷(p < 0.05)在MC组中显著增加,黄连素干预显著降低它们。BER组的熊果苷含量甚至低于NC组。第五,通过宏基因组学和代谢组学的联合分析,我们观察到粪便代谢物减少之间存在显着的负相关性(例如,熊果苷)和富集的肠道微生物群(例如,真杆菌属和瘤胃球菌属)(p < 0.05)。最后,肠道微生物群与临床指标之间的相关性分析表明,BER组中富集的细菌与上述临床指标呈负相关(p < 0.05)。结论:总之,我们的研究结果描述了肠道菌群和代谢物的变化与小檗碱改善糖和脂质代谢紊乱有关。
Introduction: Glucose and lipid metabolism disturbances has become the third major disease after cancer and cardio-cerebrovascular diseases. Emerging evidence shows that berberine can effectively intervene glucose and lipid metabolism disturbances, but the underlying mechanisms of this remain unclear. To investigate this issue, we performed metagenomic and metabolomic analysis in a group of normal mice (the NC group), mice with disturbances in glucose and lipid metabolism (the MC group) and mice with disturbances in glucose and lipid metabolism after berberine intervention (the BER group). Result: Firstly, analysis of the clinical indicators revealed that berberine significantly improved the blood glucose and blood lipid of the host. The fasting blood glucose level decreased by approximately 30% in the BER group after 8 weeks and the oral glucose tolerance test showed that the blood glucose level of the BER group was lower than that of the MC group at any time. Besides, berberine significantly reduced body weight, total plasma cholesterol and triglyceride. Secondly, compared to the NC group, we found dramatically decreased microbial richness and diversity in the MC group and BER group. Thirdly, LDA effect size suggested that berberine significantly altered the overall gut microbiota structure and enriched many bacteria, including Akkermansia (p < 0.01), Eubacterium (p < 0.01) and Ruminococcus (p < 0.01). Fourthly, the metabolomic analysis suggested that there were significant differences in the metabolomics signature of each group. For example, isoleucine (p < 0.01), phenylalanine (p < 0.05), and arbutin (p < 0.05) significantly increased in the MC group, and berberine intervention significantly reduced them. The arbutin content in the BER group was even lower than that in the NC group. Fifthly, by combined analysis of metagenomics and metabolomics, we observed that there were significantly negative correlations between the reduced faecal metabolites (e.g., arbutin) in the BER group and the enriched gut microbiota (e.g., Eubacterium and Ruminococcus) (p < 0.05). Finally, the correlation analysis between gut microbiota and clinical indices indicated that the bacteria (e.g., Eubacterium) enriched in the BER group were negatively associated with the above-mentioned clinical indices (p < 0.05). Conclusion: Overall, our results describe that the changes of gut microbiota and metabolites are associated with berberine improving glucose and lipid metabolism disturbances.
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