Sun Xiongjie, Zhang Yu, Cheng Gang, Zhu Tianxiang, Zhang Zhigang, Xiong Lei, Hu Haiming, Liu Hongtao
College of Basic Medical Sciences, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China; School of Pharmacy, Hubei University of Chinese Medicine, Huangjiahu West Road 16, Wuhan 430065, PR China.
Hubei Provincial Hospital of Traditional Chinese Medicine, Hubei University of Chinese Medicine, Wuhan 430061, PR China.
Biomed Pharmacother. 2023 Nov;167:115430. doi: 10.1016/j.biopha.2023.115430. Epub 2023 Sep 8.
Ulcerative colitis (UC) has been confirmed as a disease with a high incidence and low cure rate worldwide. In severe cases, UC can develop into colon cancer. Modern research has confirmed that berberine (BBR) can treat UC by inhibiting the expressions of inflammatory factors. However, the contribution of gut microbiota and flora metabolites in treating UC with BBR remains unclear. In this study, the ameliorative effects of BBR on gut microbiota dysbiosis and flora metabolites were investigated in a dextran sodium sulfate (DSS)-induced UC rodent model. We found that BBR significantly improved the pathological phenotype, attenuated intestinal barrier disruption, and mitigated colonic inflammation in DSS mice. By 16 S rDNA sequencing, BBR alleviated gut microbiota dysbiosis in UC mice. Moreover, the gut microbiota depletion experiment confirmed that the therapeutic effect of BBR was inextricably correlated with the gut microbiota. Besides, the flora metabolites (e.g., short-chain fatty acids, bile acids, and 5-hydroxytryptamine) were studied using HPLC-MS. The results suggested that BBR ameliorated the bile acid imbalance induced by DSS in the liver and gut. Furthermore, BBR treatment repaired gut barrier damage. The above results revealed that BBR alleviated DSS-induced UC in mice by restoring the disturbed gut microbiota, elevating unconjugated and secondary bile acids in the gastrointestinal tract, and activating the FXR and TGR5 signal pathway. This study provides novel insights into the mechanism of BBR in treating UC.
溃疡性结肠炎（UC）已被证实是一种在全球范围内发病率高且治愈率低的疾病。在严重情况下，UC可发展为结肠癌。现代研究证实，黄连素（BBR）可通过抑制炎症因子的表达来治疗UC。然而，肠道微生物群和菌群代谢产物在BBR治疗UC中的作用仍不清楚。在本研究中，我们在葡聚糖硫酸钠（DSS）诱导的UC啮齿动物模型中研究了BBR对肠道微生物群失调和菌群代谢产物的改善作用。我们发现，BBR显著改善了DSS小鼠的病理表型，减轻了肠道屏障破坏，并减轻了结肠炎症。通过16S rDNA测序，BBR减轻了UC小鼠的肠道微生物群失调。此外，肠道微生物群耗竭实验证实，BBR的治疗效果与肠道微生物群密切相关。此外，我们还使用高效液相色谱-质谱联用（HPLC-MS）研究了菌群代谢产物（如短链脂肪酸、胆汁酸和5-羟色胺）。结果表明，BBR改善了DSS诱导的肝脏和肠道胆汁酸失衡。此外，BBR治疗修复了肠道屏障损伤。上述结果表明，BBR通过恢复紊乱的肠道微生物群、提高胃肠道中未结合和次级胆汁酸水平以及激活FXR和TGR5信号通路，减轻了DSS诱导的小鼠UC。本研究为BBR治疗UC的机制提供了新的见解。
