Baitouweng Tang ameliorates DSS-induced ulcerative colitis through the regulation of the gut microbiota and bile acids via pathways involving FXR and TGR5
Baitouweng Tang ameliorates DSS-induced ulcerative colitis through the regulation of the gut microbiota and bile acids via pathways involving FXR and TGR5
复制标题
白头翁汤通过涉及 FXR 和 TGR5 的途径调节肠道微生物群和胆汁酸，改善 DSS 诱导的溃疡性结肠炎
DOI：
10.1016/j.biopha.2021.111320
复制
发表时间：
2021-02-09
影响因子：
7.5
通讯作者：
Wei, Yan-Ming
中科院分区：
文献类型：
--
作者：
Hua, Yong-Li;Jia, Ya-Qian;Wei, Yan-Ming
在中国看来，白头翁汤是治疗溃疡性结肠炎(UC)的常用药物。因此，本研究旨在评价补肾益气汤对UC BALB/c小鼠的抗结肠炎作用及其机制。在BALB/c小鼠饮水中加入3.5%的DSS，诱发小鼠UC。溃疡性结肠炎诱导后，给小鼠灌胃补肾活血汤7d。观察临床症状，用UPLC-MS/MS分析UC小鼠血清、肝脏、结肠、胆汁和粪便中的胆汁酸(BAs)，采用改良的16S rDNA高通量测序方法检测粪便中的肠道微生物区系。补肾益气汤能明显改善溃疡性结肠炎小鼠的组织学损伤、结肠缩短等临床症状。此外，补肾通便汤还能显著改善结肠炎性反应。治疗后UC中UDCA、HDCA、？MCA、？MCA、CA、GLCA升高的浓度明显降低，部分BAs尤其是CA、？MCA、？MCA水平恢复正常。此外，BTWT暴露组的相对物种丰度和肠道微生物区系多样性显著高于DSS处理组。BTWT增加了UC小鼠粪便微生物区系中的相对丰度，包括细菌、变形杆菌、放线杆菌、细菌和TM7。在DSS组，类杆菌的相对丰度在BTWT治疗后升高，并恢复正常。补肾益气汤能增加FXR和TGR5在肝脏中的表达。补肾益气汤可通过提高TGR5和FXR的表达水平，改善DSS诱导的小鼠体征。这一结果是通过对底物和肠道微生物区系的调节而实现的。
In China, Baitouweng Tang (BTWT) is a commonly prescribed remedy for the treatment of ulcerative colitis (UC). Herein, the present study aims to assess the anti-colitis activity of BTWT and its underlying mechanisms in UC BALB/c mice. Induction of UC in BALB/c mice was carried out by adding 3.5% DSS in the drinking water of underlined mice. After UC induction, the mice were administrated with BTWT for 7 days. Clinical symptoms were assessed, followed by analyzing the bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice through UPLC-MS/MS. The modified 16S rDNA high-throughput sequencing was carried out to examine the gut microbiota of feces. BTWT significantly improved the clinical symptoms such as and histological injury and colon shortening in UC induced mice. Furthermore, BTWT remarkably ameliorated colonic inflammatory response. After BTWT treatment, the increased concentrations of UDCA, HDCA, ?MCA, ?MCA, CA, and GLCA in UC were decreased, and the levels of some BAs, especially CA, ?MCA, and ?MCA were normalized. Moreover, the relative species abundance and gut microbiota diversity in the BTWT-exposed groups were found to be considerably elevated than those in the DSS-treated group. BTWT increased the relative abundance of Firmicutes, Proteobacteria, Actinobacteria, Tenericutes, and TM7, which were statistically lower in the fecal microbiota of UC mice. The relative abundance of Bacteroidetes was found to be elevated in the DSS group and normalized after BTWT treatment. BTWT increased the expression of FXR and TGR5 in the liver. BTWT administration improved DSSinduced mice signs by increasing the TGR5 and FXR expression levels. This result was achieved by the regulation of the BAs and gut microbiota.