理肠饮治疗腹泻型肠易激综合征肝郁脾虚证的临床疗效及机制研究

Clinical Efficacy and Mechanism of Lichang Beverage in the Treatment of Diarrhea-Type Irritable Bowel Syndrome with Liver Depression and Spleen Deficiency

  • 摘要:
      目的  基于菌-脑-肠轴观察理肠饮治疗腹泻型肠易激综合征(IBS-D)肝郁脾虚证的临床疗效及对血清脑肠肽、肠道菌群的影响, 探讨其可能的疗效机制。
      方法  纳入66例IBS-D肝郁脾虚证患者, 以2 ∶ 1比例随机分为中药组44例和西药组22例, 中药组予理肠饮口服, 西药组予培菲康联合得舒特口服, 疗程均为4周, 评估治疗前、治疗2周、治疗4周2组患者的IBS症状严重程度量表(IBS-SSS)评分变化, 治疗前后观察2组患者中医症状积分变化情况, 检测血清脑肠肽指标血清P物质(Substance P, SP)及5-羟色胺(Serotonin, 5-HT)表达水平及肠道菌群的组成情况。
      结果  ① 治疗2周、治疗4周, 2组IBS-SSS评分均显著降低(P < 0.01), 中药组优于西药组(P < 0.01);治疗4周后, 2组患者中医证候总积分均显著降低(P < 0.01), 中药组优于西药组(P < 0.01), 且中药组临床愈显率及总有效率均高于西药组(P < 0.05, P < 0.01)。②治疗后, 2组患者血清SP含量均明显下降(P < 0.05), 中药组血清5-HT含量显著下降(P < 0.01),2组比较无显著性差异(P>0.05)。③α多样性分析提示, 治疗后2组肠道菌群的丰富度不同程度下降(P < 0.05, P < 0.01), 西药组菌群多样性较前下降(P < 0.05), 而中药组较前无明显差异(P>0.05);PCoA分析提示2组微生物群落构成均发生明显改变(P < 0.05), 且组间比较具有显著差异(P < 0.01)。其中, 中药组治疗后有显著优势的Biomarker为Clostridium_sensu_stricto_1Bacteroides_plebeius等; 西药组治疗后有显著优势的Biomarker为ruminococcus_gnavus_group。菌群功能预测提示, 理肠饮治疗IBS-D的主要途径为糖代谢相关途径。④治疗期间2组患者均未出现与药物相关的不良反应。
      结论  中药复方理肠饮治疗IBS-D肝郁脾虚证疗效确切、安全, 其机制可能与调节血清脑肠肽水平、调整肠道菌群结构、纠正菌群失衡状态、调控糖代谢相关菌群有关。

     

    Abstract:
      OBJECTIVE  To observe the clinical efficacy of Lichang beverage in the treatment of diarrhea-type irritable bowel syndrome (IBS-D) based on the bacteria-brain-intestine axis and its effects on serum brain-gut peptide and intestinal flora, and to explore the possible mechanism of efficacy.
      METHODS  A total of 66 IBS-D patients with liver depression and spleen deficiency were randomly divided into the Chinese medicine group (44 patients) and the western medicine group (22 patients) in a 2 ∶ 1 ratio. In the Chinese medicine group, Lichang beverage was given orally. However, the patients in the western medicine group were administrated with Bifico combination with Dicetel. The treatment course lasted four weeks. Besides, the changes in the IBS-SSS scores of both groups were evaluated before treatment, as well as after two weeks and four weeks of treatment. The changes in the traditional Chinese medicine (TCM) syndrome scores of both groups were observed before and after treatment. In addition, the expression levels of serum brain-gut peptide indexes substance P (SP) and serotonin (5-HT) and the composition of intestinal flora were measured.
      RESULTS  The IBS-SSS scores of both groups were reduced significantly after two weeks and four weeks of treatment (P < 0.01), but the results in the Chinese medicine group were better than those in the western medicine group (P < 0.01). After four weeks of treatment, the total TCM syndrome scores of both groups were reduced significantly (P < 0.01), while the results in the Chinese medicine group were better than those in the western medicine group (P < 0.01). In addition, the clinical healing rate and total effective rate of the Chinese medicine group were higher than those of the western medicine group (P < 0.05, P < 0.01). After treatment, the serum SP level in both groups were reduced significantly (P < 0.05), and the serum 5-HT level in the Chinese medicine group were reduced notably (P < 0.01), but there was no significant difference between the two groups (P>0.05). The α diversity analysis indicated that the richness of intestinal flora in both groups decreased to different degrees after treatment (P < 0. 05, P < 0.01), and the diversity of flora in the western medicine group was reduced compared with that before (P < 0. 05), while there was no significant difference in the Chinese medicine group (P>0. 05). The PCoA analysis showed that the composition of microbial community in both groups changed significantly (P < 0. 05), and there were significant differences between groups (P < 0.01). Among them, the biomarkers with significant advantages after treatment in the Chinese medicine group were Clostridium_sensu_stricto_1 and Bacteroides_plebeius. However, the Biomarkers with significant advantages after treatment in the western medicine group were ruminococcus_gnavus_group. The functional prediction of the flora suggested that the main pathway of IBS-D treatment by Lichang beverage was glucose metabolism-related. Besides, no drug-related adverse reactions were observed in either group during the treatment course.
      CONCLUSION  The efficacy of Chinese herbal medicine compound — Lichang beverage in treating IBS-D with liver depression and spleen deficiency is accurate and safe. Its mechanism may be related to the regulation of serum brain-gut peptide level, adjustment of intestinal flora structure, correction of flora imbalance, and regulation of glucose metabolism-related flora.

     

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