Sino-Jan Joint Laboratory of Natural Health Products Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 639 Longmian Road, PR China; Laboratory of Systematic Forest and Forest Products Sciences, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, Fukuoka 819-0395, Japan.
Sino-Jan Joint Laboratory of Natural Health Products Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 639 Longmian Road, PR China; National Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture, Jiangsu Kanion Pharmaceutical Co., Ltd. Lianyungang, 222001, China.
Phytomedicine. 2024 Jul;129:155699. doi: 10.1016/j.phymed.2024.155699. Epub 2024 May 1.
Pulmonary Fibrosis (PF) is a progressive lung disease characterized by the diffuse interstitial tissue, leading to severe breathing difficulties. The existing treatment methods are primarily aimed at slowing the progression of the disease, underscoring the urgent need to discover new drug interventions targeting novel sites. The "gut-lung axis" represents a complex bidirectional communication system where the gut microbiota not only influences lung immunity but also responds to lung-derived signals. Recent advances have uncovered that alterations in gut microbiota composition can significantly impact respiratory diseases, offering new insights into their pathogenesis and potential therapeutic approaches.
This study is based on the fundamental concepts of the lung-gut axis and our previous research, further exploring the potential mechanisms of 20(S)-Protopanaxadiol (PPD) in ginseng against PF. We utilized a bleomycin-induced mouse model of PF and employed metabolomics and 16S rRNA sequencing to investigate the pathways through which PPD regulates the pulmonary fibrosis process via the gut-lung axis. Finally, we employed strategies such as antibiotic-induced microbiota disruption and fecal microbiota transplantation (FMT) to provide a comprehensive perspective on how PPD regulates pulmonary fibrosis through gut microbiota.
The results of the bleomycin (BLM) mouse model of PF proved that PPD can directly act on the glycolysis- related metabolic reprogramming process in lung and the AMPK/STING pathway to improve PF. Combined the analysis of gut microbiota and related metabolites, we found that PPD can regulate the process of PF through the gut-lung axis target points G6PD and SPHK1. FMT and antibiotic-induced microbiota disruption further confirmed intermediate effect of gut microbiota in PF process and the treatment of PPD. Our study suggests that PPD can alleviate the process of pulmonary fibrosis either by directly acting on the lungs or by regulating the gut microbiota.
This study positions PPD as a vanguard in the therapeutic landscape for pulmonary fibrosis, offering a dual mechanism of action that encompasses both modulation of gut microbiota and direct intervention at molecular targets. These insights highlight the immense therapeutic potential of harnessing the gut-lung axis.
肺纤维化（PF）是一种弥漫性间质组织的进行性肺部疾病，导致严重的呼吸困难。现有的治疗方法主要旨在减缓疾病的进展，突显了迫切需要发现针对新靶点的新药物干预措施。“肠-肺轴”代表了一个复杂的双向通讯系统，其中肠道微生物群不仅影响肺免疫，而且对肺部来源的信号做出反应。最近的进展揭示了肠道微生物群组成的改变可以显著影响呼吸系统疾病，为其发病机制和潜在治疗方法提供了新的见解。
本研究基于肺-肠轴的基本概念和我们以前的研究，进一步探索 20(S)-原人参二醇（PPD）在人参防治 PF 中的潜在机制。我们利用博来霉素诱导的 PF 小鼠模型，运用代谢组学和 16S rRNA 测序技术，研究 PPD 通过肠-肺轴调节肺纤维化过程的途径。最后，我们采用抗生素诱导的微生物群破坏和粪便微生物群移植（FMT）等策略，全面探讨 PPD 通过肠道微生物群调节肺纤维化的机制。
博来霉素（BLM）诱导的 PF 小鼠模型的结果表明，PPD 可以直接作用于肺中的糖酵解相关代谢重编程过程和 AMPK/STING 通路，改善 PF。结合肠道微生物群和相关代谢物的分析，我们发现 PPD 可以通过肠-肺轴靶点 G6PD 和 SPHK1 调节 PF 过程。FMT 和抗生素诱导的微生物群破坏进一步证实了肠道微生物群在 PF 过程中的中间作用以及 PPD 的治疗作用。我们的研究表明，PPD 可以通过直接作用于肺部或调节肠道微生物群来缓解肺纤维化过程。
本研究将 PPD 定位为肺纤维化治疗领域的先锋，提供了一种双重作用机制，包括调节肠道微生物群和直接作用于分子靶点。这些发现突出了利用肠-肺轴的巨大治疗潜力。
