中药对肠道菌群结构和功能作用的研究

doi:10.5246/jcps.2020.03.014

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (3): 161-175.DOI: 10.5246/jcps.2020.03.014

中药对肠道菌群结构和功能作用的研究

田思聪¹, 薛婧^2*, 宋辉^3*, 杜权^1*

1. 北京大学医学部药学院天然药物及仿生药物国家重点实验室, 北京 100191
2. 解放军总医院第三医疗中心, 北京 100039
3. 航空航天中心医院, 北京 100039

收稿日期:2019-12-12 修回日期:2020-01-18 出版日期:2020-03-30 发布日期:2020-02-17
通讯作者: Tel.: +86-10-82805780, E-mail: quan.du@pku.edu.cn; Tel.: +86-15600668870, E-mail: imxuej@163.com; Tel.: +86-13671337230, E-mail: songhui731@sina.com
基金资助:
The National Natural Science Foundation of China (Grant No. 31571403), Beijing Natural Science Foundation (Grant No. 2171001).

Regulatory effects of traditional Chinese medicine on intestinal flora

Sicong Tian¹, Jing Xue^2*, Hui Song^3*, Quan Du^1*

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. The Third Medical Center of Chinese People’s Liberation Army General Hospital, Beijing 100039, China
3. Aeropace Central Hospital, Beijing 100039, China

Received:2019-12-12 Revised:2020-01-18 Online:2020-03-30 Published:2020-02-17
Contact: Tel.: +86-10-82805780, E-mail: quan.du@pku.edu.cn; Tel.: +86-15600668870, E-mail: imxuej@163.com; Tel.: +86-13671337230, E-mail: songhui731@sina.com
Supported by:
The National Natural Science Foundation of China (Grant No. 31571403), Beijing Natural Science Foundation (Grant No. 2171001).

摘要/Abstract

摘要：

为了探讨中草药对肠道菌群的调节作用, 我们选择王氏保赤丸和三七总皂甙两种具有悠久应用历史的中药开展本研究。研究模型为雄性Wistar大鼠, 分为高中低三个剂量组, 连续给药28天。给药结束后, 收集大鼠的新鲜粪便进行16S rRNA测序, 以确定肠道菌群的组成谱。与对照组相比, 发现王氏保赤丸对乳酸杆菌和拟杆菌的丰度产生了平衡的调节作用, 这与其对便秘和腹泻独特的双向作用是一致的。研究进一步发现, 王氏保赤丸给药提高了短链脂肪酸生产菌Ruminiclostridium_9和Eubacterium_ventriosum的丰度, 减少了与炎症相关的Jeotgalicoccus和Bilophila属的丰度, 使大鼠肠道菌群的整体组成更加健康。对三七总皂甙给药组的研究发现, 三七总皂甙对与帕金森氏病相关的肠杆菌科, 与衰老相关的Christensenellaceae菌科、以及与高血压有关的Rikenellaceae、Christensenellaceae、Lachnospiraceae和Bacteroidaceaceae菌属均具有显著的调节作用, 这些作用与其主要的临床适应症是相符的, 三七总皂甙给药还能提高短链脂肪酸生产菌群的丰度, 包括Elusimicrobium、Anaerotruncus、Ruminococcaceae_NK4A214_group和Intestinimonas。对王氏保赤丸和三七总皂甙的研究表明, 两种中药不仅对肠道菌群具有各自特征性的调节作用, 这些调节作用还与它们独特的临床治疗效果相一致, 提示我们肠道菌群极有可能参与了王氏保赤丸和三七总皂甙对疾病的治疗过程。

关键词: 肠道菌群, 中药, 16S rRNA测序

Abstract:

Two traditional Chinese medicines (TCMs), namely WangshiBaochiwan and Panax Notoginseng Saponins (notoginsenoside),were chosen to study their effects on gut microbiota. Both of them have a long history of application in China. During a test of 28 d, different doses of the medicines were administered to male Wistar rats daily. At the end of the administration, fresh fecal samples were collected and subjected to 16S rRNA sequencing to determine the profiles of gut microbiota. In relative to the controls, effects on gut microbiota were evaluated with medicine-treated rats. Consistent with its unique bidirectional effects on constipation and diarrhea, treatment of WangshiBaochiwan led to a balanced regulation of Lactobacillus and Bacteroides. The treatment also led to increased populations of Ruminiclostridium_9 and Eubacterium_ventriosum that are the major producer of short-chain fatty acid (SCFA), and decreased populations of genus Jeotgalicoccus and Bilophila that are associated with inflammation. These changes therefore resulted in a much healthier microbiota environment in WangshiBaochiwan-treated rates. For the treatmentof notoginsenoside, effects were found with Enterobacteriaceae species that is associated with Parkinson's disease, Christensenellaceaefamily that is associated with aging, and hypertension-associated Rikenellaceae, Christensenellaceae, Lachnospiraceae and Bacteroidaceae species. In agreement with its major indications, the treatment further led to increased populations of SCFA-producingbacteria, such as Elusimicrobium, Anaerotruncus, Ruminococcaceae_NK4A214_group, and Intestinimonas. Taken together, treatment of the two TCMs led to active and distinguishable regulations of gut microbiota. Impressively, these changes were in agreement with their clinical efficacy, and suggested that they were involved in the treatment of these diseases.

Key words: Intestinal flora, Traditional Chinese medicine, Deep sequencing

中图分类号:

R962

Supporting:

Supplementary Table 1. Effect of total saponins of Panax notoginseng, JinghuaBaochi Pills and antibiotics on organ coefficient of mice (g/100g, ±s, n = 5)

The heart, liver, spleen, lung and kidney coefficient of mice were compared, and the liver weight of antibiotic group was significantly changed (^*P<0.05).The control group (group C), the low-medium-high dose group (J_low, J_middle, J_high group) of JinghuaBaochi Wan, the low-medium-high dose group of Panax notoginseng saponins (P_low, P_middle, P_high group) and the antibiotic group (A_group)

Supplementary Figure 1. Wilcoxon rank sum test of the control group and the JinghuaBaochi pill administration group. The vertical axis represents the species name at a certain classification level, each column corresponding to the species represents the average relative abundance of the species in each sample group, and the different colors indicate different groupings. The rightmost side is the P value, ^*0.01<P≤0.05, ^**0.001<P≤0.01, ^***P≤0.001.Test method wilcoxon rank sum test, two-tail test, multiple test correction fdr, significance level less than 0.05 bacteria are shown in this figure.

Supplementary Figure 2. Rank sum test of Panax notoginseng saponins group and control group. The vertical axis represents the species name at a certain classification level, each column corresponding to the species represents the average relative abundance of the species in each sample group, and the different colors indicate different groupings. The rightmost side is the P value, ^*0.01<P≤0.05, ^**0.001<P≤0.01, ^***P≤0.001. Red indicates a control group (group C), and blue indicates a drug-administered group (group P).

田思聪, 薛婧, 宋辉, 杜权. 中药对肠道菌群结构和功能作用的研究[J]. 中国药学(英文版), 2020, 29(3): 161-175.

Sicong Tian, Jing Xue, Hui Song, Quan Du. Regulatory effects of traditional Chinese medicine on intestinal flora[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(3): 161-175.

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中药对肠道菌群结构和功能作用的研究

Regulatory effects of traditional Chinese medicine on intestinal flora

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