麻杏石甘汤通过调节肠道菌群-色氨酸代谢-ILC2轴减轻过敏性哮喘
Ma-Xing-Shi-Gan decoction alleviates allergic asthma by modulating the gut microbiota-tryptophan metabolism-ILC2 axis.
摘要(中文译文)
麻杏石甘汤（MXSG）在哮喘中显示出临床疗效，但其如何塑造肠-肺免疫——尤其是2型固有淋巴样细胞应答——仍不清楚。旨在探讨麻杏石甘汤是否通过肠道菌群-色氨酸代谢途径抑制2型固有淋巴样细胞（ILC2s）从而缓解哮喘，并鉴定菌群依赖性活性化合物。采用哮喘小鼠模型。通过流式细胞术评估肺和肠固有层中的ILC2。使用Rag1小鼠评估不依赖T细胞和B细胞的效应。进行非靶向粪便代谢组学和抗生素介导的菌群耗竭，以评估代谢和微生物的贡献。采用厌氧粪便发酵结合LC-MS/MS谱分析追踪菌群依赖性麻杏石甘汤成分，随后进行体内验证。麻杏石甘汤显著减轻肺部炎症，减少支气管肺泡灌洗液中的嗜酸性粒细胞，并改善组织病理学。它减少了肺和肠道中的ILC2群体。这些效应在Rag1小鼠中得以保留，但在抗生素预处理后被消除，表明其依赖于菌群。代谢组学揭示麻杏石甘汤重编程了色氨酸代谢，恢复了色胺并重新平衡了犬尿氨酸、吲哚和血清素相关分支。厌氧发酵和LC-MS/MS谱分析鉴定出菌群依赖性黄酮类化合物，而异鼠李素在体内部分重现了抗炎和调节ILC2的效应。麻杏石甘汤通过肠道菌群-色氨酸代谢-ILC2轴发挥其抗哮喘效应。这些发现揭示了一种以2型固有免疫和菌群来源吲哚代谢为核心的新型肠-肺机制。
Abstract
Ma-Xing-Shi-Gan decoction (MXSG) shows clinical efficacy in asthma, yet how it shapes gut-lung immunity-particularly type 2 innate lymphoid responses-remains poorly defined. To investigate whether MXSG mitigates asthma by restraining group 2 innate lymphoid cells (ILC2s) via a gut microbiota-tryptophan metabolic pathway, and to identify microbiota-dependent active compounds. An asthma mouse model was used. ILC2 in the lung and intestinal lamina propria were assessed by flow cytometry. Rag1 mice were used to assess T and B cell-independent effects. Untargeted fecal metabolomics and antibiotic-mediated microbiota depletion were conducted to evaluate metabolic and microbial contributions. Microbiota-dependent MXSG constituents were traced using anaerobic fecal fermentation coupled with LC-MS/MS profiling, followed by in vivo validation. MXSG significantly alleviated pulmonary inflammation, reduced bronchoalveolar lavage eosinophils and improved histopathology. It decreased ILC2s populations in lung and gut. These effects were preserved in Rag1 mice but abolished with antibiotics pretreatment, indicating microbiota dependence. Metabolomics revealed that MXSG reprogrammed tryptophan metabolism, restoring tryptamine and rebalancing kynurenine, indole, and serotonin-related branches. Anaerobic fermentation and LC-MS/MS profiling identified microbiota-dependent flavonoids, and isorhamnetin partially reproduced the anti-inflammatory and ILC2-modulating effects in vivo. MXSG exerts its anti-asthmatic effects via the gut microbiota-tryptophan metabolism-ILC2 axis. These findings reveal a novel gut-lung mechanism centered on type 2 innate immunity and microbiota-derived indole metabolism.
如何引用
AMA
Mengmeng Lv, Chen Wang, Yanfei Hong, Fei Ye, Xiaoyu Cao, Zhixin Zheng, et al. Ma-Xing-Shi-Gan decoction alleviates allergic asthma by modulating the gut microbiota-tryptophan metabolism-ILC2 axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158378.
APA
Mengmeng Lv, Chen Wang, Yanfei Hong, Fei Ye, Xiaoyu Cao, Zhixin Zheng, et al (2026). Ma-Xing-Shi-Gan decoction alleviates allergic asthma by modulating the gut microbiota-tryptophan metabolism-ILC2 axis.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158378
GB/T 7714
Mengmeng Lv, Chen Wang, Yanfei Hong, Fei Ye, Xiaoyu Cao, Zhixin Zheng, et al. Ma-Xing-Shi-Gan decoction alleviates allergic asthma by modulating the gut microbiota-tryptophan metabolism-ILC2 axis.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158378.
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