Table1_Bu-Fei-Huo-Xue capsule alleviates bleomycin-induced pulmonary fibrosis in mice through modulating gut microbiota.DOCX

Introduction: Bu-Fei-Huo-Xue capsule (BFHX) has been used to treat pulmonary fibrosis (PF) in clinic. However, the mechanism of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis remains unclear. Recent studies have shown that the changes in gut microbiota were closely related to the progression of pulmonary fibrosis. Modulating gut microbiota provides new thoughts in the treatment of pulmonary fibrosis.
Methods: In this study,a mouse model of pulmonary fibrosis was induced using bleomycin (BLM) and treated with Bu-Fei-Huo-Xue capsule. We firstly evaluated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis model mice. Besides,the anti-inflammatory and anti- oxidative effects of Bu-Fei-Huo-Xue capsule were evaluated. Furthermore, 16S rRNA sequencing was used to observe the changes in gut microbiota in pulmonary fibrosis model mice after Bu-Fei-Huo-Xue capsule treatment.
Results: Our results showed that Bu-Fei-Huo-Xue capsule significantly reduced the collagen deposition in pulmonary fibrosis model mice. Bu-Fei-Huo-Xue capsule treatment also reduced the levels and mRNA expression of pro-inflammatory cytokines and inhibited the oxidative stress in lung. 16S rRNA sequencing showed that Bu-Fei-Huo-Xue capsule affected the diversity of gut microbiota and the relative abundances of gut microbiota such as Lactobacillus, Lachnospiraceae_NK4A136_group, and Romboutsia.
Conclusion: Our study demonstrated the therapeutic effects of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis. The mechanisms of Bu-Fei-Huo-Xue capsule on pulmonary fibrosis may be associated with regulating gut microbiota.

引言：补肺活血胶囊（Bu-Fei-Huo-Xue capsule, BFHX）已在临床中用于治疗肺纤维化（pulmonary fibrosis, PF），但其治疗肺纤维化的具体机制尚未明确。近期研究表明，肠道菌群（gut microbiota）的变化与肺纤维化的进展密切相关，调控肠道菌群为肺纤维化的治疗提供了新思路。
方法：本研究采用博莱霉素（bleomycin, BLM）诱导建立肺纤维化小鼠模型，并给予补肺活血胶囊干预。首先评估补肺活血胶囊对肺纤维化模型小鼠的治疗效果；其次检测补肺活血胶囊的抗炎与抗氧化作用；此外，采用16S rRNA测序（16S rRNA sequencing）分析补肺活血胶囊干预后肺纤维化模型小鼠的肠道菌群变化。
结果：本研究结果显示，补肺活血胶囊可显著减轻肺纤维化模型小鼠的胶原沉积；补肺活血胶囊治疗还可降低促炎细胞因子（pro-inflammatory cytokines）的水平及其mRNA表达，并抑制肺部氧化应激（oxidative stress）。16S rRNA测序结果表明，补肺活血胶囊可改变肠道菌群的多样性，以及乳杆菌属（Lactobacillus）、毛螺菌科_NK4A136群（Lachnospiraceae_NK4A136_group）、罗姆布茨菌属（Romboutsia）等肠道菌群的相对丰度。
结论：本研究证实了补肺活血胶囊对肺纤维化的治疗作用，其治疗肺纤维化的潜在机制可能与调控肠道菌群相关。