Table_1_Mahuang Fuzi Xixin decoction ameliorates allergic rhinitis and repairs the airway epithelial barrier by modulating the lung microbiota dysbiosis.doc

BackgroundAllergic rhinitis (AR) is a common disorder, that burdens general well-being. Although the lung is connected to the upper respiratory tract, which is rich in microorganisms, no studies have reported the relationship between lung microbiota and AR. Mahuang Fuzi Xixin decoction (MFXD) is a traditional Chinese medicine (TCM) formula that is widely used to treat AR in the clinic but its underlying mechanism remains unclear.
HypothesisWe hypothesized that lung microbiota is associated with the pathogenesis of AR, and MFXD can improve AR by regulating microbiota dysbiosis.
MethodsThe ovalbumin-induced mouse AR model was used to evaluate the therapeutic effect of MFXD on AR. Then 16S rDNA amplicon sequencing, untargeted metabolomics, and other molecular biology technology were used to clarify the effects of MFXD on lung microbes dysbiosis and AR progression. Further, the human nasal epithelial cell line (HNEpCs) was used to evaluate the protective effect of MFXD on epithelial barrier damage caused by specific pathogens.
ResultsMFXD decreased plasma histamine and IgE levels, ameliorated pathological damage, and diminished the expression of tight junction proteins (ZO-1 and occludin) in lung and nasal tissues. MFXD altered AR-induced microbiota dysbiosis in the lungs and also plasma metabolites. Oral administration of MFXD altered microbiota dysbiosis in lung and AR-associated metabolic disorders. The dominant bacteria in the lungs of AR mice damaged the airway barrier, and MFXD reversed this change.
ConclusionThis study revealed the correlation between the lung microbiota and AR in the mice model. We confirmed that lung microbiota plays a vital role in AR and that MFXD reduced damage to the epithelial barrier of the lungs and nasal mucosa by regulating lung microbiota and plasma metabolism imbalances. Our research provides a reference for the effect of lung microbiota on AR and provides a new idea for the treatment of AR.

研究背景：变应性鼻炎（Allergic rhinitis, AR）是一种常见疾病，会对患者的整体健康状态造成负担。尽管肺与富含微生物群的上呼吸道相连，但目前尚无研究报道肺微生物群（lung microbiota）与变应性鼻炎之间的关联。麻黄附子细辛汤（Mahuang Fuzi Xixin decoction, MFXD）是一种临床中广泛用于治疗变应性鼻炎的中药方剂（traditional Chinese medicine, TCM），但其具体作用机制尚未明确。
研究假说：我们推测肺微生物群与变应性鼻炎的发病机制存在关联，且麻黄附子细辛汤可通过调节微生物群失调改善变应性鼻炎。
研究方法：本研究采用卵清蛋白诱导的小鼠变应性鼻炎模型，评估麻黄附子细辛汤对变应性鼻炎的治疗效果。随后通过16S rDNA扩增子测序、非靶向代谢组学及其他分子生物学技术，阐明麻黄附子细辛汤对肺微生物群失调及变应性鼻炎进展的调控作用。此外，本研究还利用人鼻上皮细胞系（Human nasal epithelial cell line, HNEpCs），评估麻黄附子细辛汤对特定病原体所致上皮屏障损伤的保护作用。
研究结果：麻黄附子细辛汤可降低血浆组胺与免疫球蛋白E（IgE）水平，减轻病理损伤，并下调肺与鼻组织中紧密连接蛋白（tight junction proteins, ZO-1和occludin）的表达。麻黄附子细辛汤可改善变应性鼻炎诱导的肺微生物群失调及血浆代谢物异常。口服给药的麻黄附子细辛汤可调节肺微生物群失衡，并改善变应性鼻炎相关的代谢紊乱。变应性鼻炎模型小鼠肺部的优势菌可破坏气道屏障，而麻黄附子细辛汤可逆转这一改变。
研究结论：本研究在小鼠模型中揭示了肺微生物群与变应性鼻炎之间的关联。我们证实，肺微生物群在变应性鼻炎的发生发展中发挥关键作用，而麻黄附子细辛汤可通过调控肺微生物群及血浆代谢失衡，减轻肺与鼻黏膜上皮屏障的损伤。本研究为肺微生物群对变应性鼻炎的影响提供了参考依据，同时为变应性鼻炎的治疗提供了全新思路。