Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA.
Thoracic Disease Research Unit, Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Respir Res. 2023 May 31;24(1):144. doi: 10.1186/s12931-023-02422-5.
The gut-lung axis is the concept that alterations of gut microbiota communities can influence immune function in the lungs. While studies have explored the relationship between intestinal bacterial dysbiosis and asthma development, less is understood about the impact of commensal intestinal fungi on asthma severity and control and underlying mechanisms by which this occurs.
Wild-type mice were treated with Cefoperazone to deplete gut bacteria and administered Candida albicans or water through gavage. Mice were then sensitized to house dust mite (HDM) and their lungs were analyzed for changes in immune response. Humans with asthma were recruited and stool samples were analyzed for Candida abundance and associations with asthma severity and control.
Mice with intestinal Candida dysbiosis had enhanced Th2 response after airway sensitization with HDM, manifesting with greater total white cell and eosinophil counts in the airway, and total IgE concentrations in the serum. Group 2 innate lymphoid cells (ILC2) were more abundant in the lungs of mice with Candida gut dysbiosis, even when not sensitized to HDM, suggesting that ILC2 may be important mediators of the enhanced Th2 response. These effects occurred with no detectable increased Candida in the lung by culture or rtPCR suggesting gut-lung axis interactions were responsible. In humans with asthma, enhanced intestinal Candida burden was associated with the risk of severe asthma exacerbation in the past year, independent of systemic antibiotic and glucocorticoid use.
Candida gut dysbiosis may worsen asthma control and enhance allergic airway inflammation, potentially mediated by ILC2. Further studies are necessary to examine whether microbial dysbiosis can drive difficult-to-control asthma in humans and to better understand the underlying mechanisms.
肠-肺轴是指肠道微生物群落的改变会影响肺部的免疫功能的概念。虽然已有研究探讨了肠道细菌失调与哮喘发展之间的关系，但对于共生肠道真菌对哮喘严重程度和控制的影响以及发生这种情况的潜在机制了解较少。
使用头孢哌酮处理野生型小鼠以耗尽肠道细菌，并通过灌胃给予白色念珠菌或水。然后使小鼠对屋尘螨（HDM）致敏，并分析其肺部免疫反应的变化。招募患有哮喘的患者，并分析粪便样本中白色念珠菌的丰度及其与哮喘严重程度和控制的关联。
肠道白色念珠菌失调的小鼠在气道致敏后具有增强的 Th2 反应，表现为气道中总白细胞和嗜酸性粒细胞计数增加，血清中总 IgE 浓度增加。即使未对 HDM 致敏，具有白色念珠菌肠道失调的小鼠肺部的 2 型固有淋巴细胞（ILC2）也更为丰富，这表明 ILC2 可能是增强的 Th2 反应的重要介质。这些作用发生时，通过培养或 rtPCR 都无法在肺部检测到白色念珠菌的增加，表明肠-肺轴相互作用是导致这些现象的原因。在患有哮喘的人群中，增强的肠道白色念珠菌负担与过去一年严重哮喘恶化的风险相关，与全身性抗生素和糖皮质激素的使用无关。
白色念珠菌肠道失调可能会使哮喘控制恶化并增强过敏性气道炎症，可能由 ILC2 介导。需要进一步研究以检查微生物失调是否会导致人类难以控制的哮喘，并更好地理解潜在机制。
