Gu-Ben-Fang-Xiao Decoction Ameliorated Murine Asthma in Remission Stage by Modulating Microbiota-Acetate-Tregs Axis
Gu-Ben-Fang-Xiao Decoction Ameliorated Murine Asthma in Remission Stage by Modulating Microbiota-Acetate-Tregs Axis
复制标题
固本防效汤通过调节微生物-乙酸-Tregs轴改善缓解期小鼠哮喘
DOI：
10.3389/fphar.2020.00549
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发表时间：
2020-05-04
影响因子：
5.6
通讯作者：
Ji, Jianjian
中科院分区：
文献类型：
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作者：
Dong, Yingmei;Yan, Hua;Ji, Jianjian
肠道菌群失调是哮喘发病机制中的关键因素。操纵肠道微生物群是一种有前途的哮喘治疗干预措施，正在广泛研究。固本防哮汤是治疗哮喘缓解期的有效方剂。在此，我们表明，GBFXD治疗显着减轻ARS通过改善呼吸功能和肺组织病理学。哮喘小鼠表现出肠道微生物群的生态失调，表现为肠道中拟杆菌属的丰度显著增加和厚壁菌门的丰度降低，而GBFXD治疗在门、科和属水平上逆转了哮喘小鼠的肠道生态失调。此外，我们的数据表明，GBFXD治疗增加了哮喘小鼠中短链脂肪酸（SCFA）产生细菌的丰度，如厚壁菌门（Firmicutes）、毛螺菌科（Lachnospiraceae）和双歧杆菌科（Bioproteinbacteriaceae），从而导致SCFA水平升高。此外，GBFXD治疗显著增强了哮喘小鼠中通过SCFA，特别是乙酸盐的调节性T细胞分化。更重要的是，GBFXD的保护作用被证明是通过共同住房微生物群移植在哮喘小鼠中传播的。抗生素混合物和乙酸盐补充实验也进一步证实了产生SCFA的肠道微生物群在GBFXD作用中的重要性。因此，我们首次证明了ARS中存在肠道微生物群失调。GBFXD可通过微生物-乙酸盐-乳酸盐轴改善ARS。
Dysbiosis of gut microbiota is a critical factor in the pathogenesis of asthma. Manipulating gut microbiota is a promising therapeutic intervention in asthma, and is being extensively studied. Gu-Ben-Fang-Xiao Decoction (GBFXD), derived from traditional Chinese medicine, is an effective and safe therapeutic formula for asthma in remission stage (ARS). Herein, we showed that GBFXD treatment remarkably alleviated ARS by improving respiratory function and lung histopathology. Asthmatic mice displayed a dysbiosis of gut microbiota, represented by significantly increased abundance of Bacteroidetes and decreased abundance of Firmicutes in gut, while GBFXD treatment reversed the gut dysbiosis in asthmatic mice at phylum, family, and genus levels. Moreover, our data showed that GBFXD treatment increased the abundance of short-chain fatty acid (SCFA)-producing bacteria in asthmatic mice, such as Firmicutes, Lachnospiraceae, and Bifidobacteriaceae, which consequently led to elevated levels of SCFAs. Furthermore, GBFXD treatment significantly enhanced the regulatory T cell differentiation via SCFAs, particularly acetate, in asthmatic mice. More critically, the protective effect of GBFXD was shown to be transmissible among asthmatic mice through co-housing microbiota transplantation. Antibiotic cocktail and acetate replenishment experiments also further substantiated the importance of SCFA-producing gut microbiota in GBFXD action. We, thus, demonstrated for the first time that gut microbiota dysbiosis existed in ARS. GBFXD could ameliorate ARS through the microbiota-acetate-Tregs axis.