Liang Xuejuan, Wan Dan, Li Xinliang, Peng Yanmei, Chen Linglong
Institute of Innovative Traditional Chinese Medicine, Hunan Academy of Chinese Medicine, Changsha, China.
Scientific Research Department, Hunan Academy of Chinese Medicine, Changsha, China.
Front Cell Infect Microbiol. 2025 Jan 7;14:1524327. doi: 10.3389/fcimb.2024.1524327. eCollection 2024.
This study aims to explore the therapeutic mechanism of Massa Medicata Fermentata (MMF) with different formulations on spleen deficiency constipation in mice by analyzing gastrointestinal hormones, D-xylose, intestinal microbiota, and intestinal enzyme activities.
A spleen deficiency constipation model was established using an oral administration of Sennae Folium decoction combined with controlled diet and water intake. After successful model establishment, the mice with spleen deficiency constipation were treated with MMF S1, S2, S3. Following the intervention, serum samples from each group of mice were collected to measure VIP, 5-HT, and D-xylose. Additionally, small intestine contents were analyzed for intestinal enzyme activity and subjected to 16S rRNA high-throughput sequencing.
Mice with spleen deficiency constipation showed significant decreases in body weight and fecal water content. In contrast, the body weight of the CS2 and CS3 groups returned to normal levels, and fecal water content in the CS2 and CS3 groups also returned to normal. The MMF S2 and S3 significantly increased protease and sucrase enzymes levels compared with CM group. Serum D-xylose levels were significantly reduced in the CM and CS2 group. VIP levels increased significantly in the CM group but decreased in the CS2 and CS3 groups. Additionally, 5-HT levels in the CM and CS1 groups decreased significantly, with the CS2 group returning to normal and the CS3 group showing significant increases. 16S rRNA sequencing analysis revealed that all three MMF formulations effectively restored the intestinal microbiota composition in mice. LEfSe analysis identified characteristic microbiota linked to different intervention groups. The CS3 group significantly upregulated the chloroalkane and chloroalkene degradation and vibrio cholerae pathogenic cycle pathways compared to the CM group. in the CS3 group and in the CS2 group were positive and negative correlations with 5-HT and VIP, respectively.
The three formulations of MMF significantly alleviated spleen deficiency constipation symptoms by modulating intestinal enzyme activities, D-xylose, VIP, and 5-HT levels, and restoring intestinal microbiota balance. and were identified as potential biomarkers for the treatment of spleen deficiency constipation. Different formulations of MMF have different mechanisms of regulating constipation through intestinal microbiota.
本研究旨在通过分析胃肠激素、D-木糖、肠道微生物群和肠道酶活性，探讨不同配方的六神曲对小鼠脾虚便秘的治疗机制。
采用口服番泻叶汤联合控制饮食和饮水建立脾虚便秘模型。模型成功建立后，用六神曲S1、S2、S3治疗脾虚便秘小鼠。干预后，收集每组小鼠的血清样本，检测血管活性肠肽（VIP）、5-羟色胺（5-HT）和D-木糖。此外，分析小肠内容物的肠道酶活性，并进行16S rRNA高通量测序。
脾虚便秘小鼠体重和粪便含水量显著降低。相比之下，CS2组和CS3组小鼠体重恢复至正常水平，CS2组和CS3组粪便含水量也恢复正常。与模型组相比，六神曲S2和S3显著提高了蛋白酶和蔗糖酶水平。模型组和CS2组血清D-木糖水平显著降低。模型组VIP水平显著升高，CS2组和CS3组则降低。此外，模型组和CS1组5-HT水平显著降低，CS2组恢复正常，CS3组显著升高。16S rRNA测序分析表明，三种六神曲配方均能有效恢复小鼠肠道微生物群组成。线性判别分析效应大小（LEfSe）分析确定了与不同干预组相关的特征微生物群。与模型组相比，CS3组显著上调了氯代烷烃和氯代烯烃降解以及霍乱弧菌致病周期途径。CS3组中的 与5-HT呈正相关，CS2组中的 与VIP呈负相关。
六神曲的三种配方通过调节肠道酶活性、D-木糖、VIP和5-HT水平，恢复肠道微生物群平衡，显著缓解脾虚便秘症状。 和 被确定为治疗脾虚便秘的潜在生物标志物。六神曲的不同配方通过肠道微生物群调节便秘的机制不同。
