DataSheet1_Shen-Ling-Bai-Zhu-San (SL) and SL Derived-Polysaccharide (PL) Ameliorate the Severity of Diarrhea-Induced by High Lactose via Modification of Colonic Fermentation.docx

In our previous study, we demonstrated that Shen-ling-bai-zhu-san (SL), a classical Chinese herbal formula, could alleviate lactose-induced diarrhea. However, little is known about the mechanism underlying SL action or the efficacy of the polysaccharide (PL) derived from SL. In this study, we investigated the effect of SL and PL on improving the dysregulated luminal and mucosal microbiota in rats with high lactose diet using 16S rRNA analysis. The concentrations of lactose, lactic acid in cecum and short-chain fatty acids (SCFAs) in cecum and portal vein were measured, meanwhile the expression of ion transporters were ascertained. Our data suggest that the SL, PL and cecal microbiota transplantation (CMT) significantly decreased fecal water content and water intake. In the luminal microbiota there was a significant increase in Akkermansia, Bifidobacterium and Blautia and a lower abundance of Lactobacillus, Escherichia-Shigella, and Dubosiella, while the mucosal microbiota showed a significant increase in Bifidobacterium, Akkermansia, Albaculum, Bilophila, and Coriobacteriaceae_UCG-002 and a lower abundance of Enterococcus, Helicobacter, Dubosiella, and Collinsella. Furthermore, the treatments enhanced lactose fermentation and SCFA production, which may be related to the modulation of the luminal microbial community. A lower ratio of phosphorylation Na/H exchanger3/Na/H exchanger3 (pNHE3/NHE3) and a higher sodium monocarboxylate1 (sMCT1) expression were found in the treatment group than in the model group, which may be related to the changes in the mucosal microbial community. Also, the treatments may restore the impacted metabolic pathways of gut microbiota. These results provide an important foundation for mechanism of SL action and developing PL-based treatment for lactose-induced diarrhea.

在前期的研究中，我们已证实经典中药方剂——沈灵百芷散（SL），能够缓解乳糖引起的腹泻。然而，关于SL的作用机制或从SL中提取的多糖（PL）的有效性知之甚少。在本研究中，我们采用16S rRNA分析技术，探究了SL和PL对高乳糖饮食大鼠肠腔和黏膜菌群失调的改善作用。我们测量了盲肠中乳糖、乳酸的含量以及盲肠和门静脉中的短链脂肪酸（SCFA）浓度，同时确定了离子转运蛋白的表达。我们的数据显示，SL、PL及盲肠菌群移植（CMT）显著降低了粪便水分含量和水摄入量。在肠腔菌群中，阿克曼氏菌、双歧杆菌和布劳提亚数量显著增加，而乳酸杆菌、大肠杆菌-志贺菌和都波氏菌的丰度降低；而在黏膜菌群中，双歧杆菌、阿克曼氏菌、阿巴库姆、比洛菲拉和科里奥巴菌科UCG-002的丰度显著增加，而肠球菌、幽门螺杆菌、都波氏菌和柯林斯菌的丰度降低。此外，治疗提高了乳糖发酵和SCFA的产生，这可能与肠腔微生物群的调节有关。与对照组相比，治疗组中磷酸化Na/H交换体3/Na/H交换体3（pNHE3/NHE3）的比值降低，钠单羧酸盐1（sMCT1）的表达升高，这可能与其黏膜微生物群的变化有关。此外，治疗可能恢复了受损的肠道微生物群的代谢途径。这些结果为SL的作用机制及其在乳糖引起腹泻的PL基治疗中的应用提供了重要的理论基础。