澳大利亚莫纳什大学 Benjamin J. Marsland、Tomasz P. Wypych研究组揭示了L-酪氨酸的微生物降解可防止过敏性气道炎症。该项研究成果发表在2021年1月25日出版的《自然-免疫学》上。

使用小鼠有限抗体库模型，研究人员确定了抗体-微生物相互作用在重塑细菌群落过程中增强了L-酪氨酸代谢。这种作用导致对甲酚硫酸盐（PCS）浓度升高，从而保护宿主抵抗过敏性气道炎症。由于表皮生长因子受体（EGFR）和Toll样受体4（TLR4）信号解偶联，PCS选择性降低了气道上皮细胞CCL20的产生。

这些数据共同揭示了肠道微生物衍生代谢产物的途径，该途径作用于远端气道上皮细胞从而减少过敏性气道反应，例如减弱哮喘的反应。

研究人员表示，肠道微生物组的组成由其生活环境决定，而该环境本身是由免疫压力（如粘膜IgA）形成。

附：英文原文

Title: Microbial metabolism of l -tyrosine protects against allergic airway inflammation

Author: Tomasz P. Wypych, Cline Pattaroni, Olaf Perdijk, Carmen Yap, Aurlien Trompette, Dovile Anderson, Darren J. Creek, Nicola L. Harris, Benjamin J. Marsland

Issue&Volume: 2021-01-25

Abstract: The constituents of the gut microbiome are determined by the local habitat, which itself is shaped by immunological pressures, such as mucosal IgA. Using a mouse model of restricted antibody repertoire, we identified a role for antibody–microbe interactions in shaping a community of bacteria with an enhanced capacity to metabolize L-tyrosine. This model led to increased concentrations of p-cresol sulfate (PCS), which protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells due to an uncoupling of epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4) signaling. Together, these data reveal a gut microbe–derived metabolite pathway that acts distally on the airway epithelium to reduce allergic airway responses, such as those underpinning asthma.

DOI: 10.1038/s41590-020-00856-3

Source: https://www.nature.com/articles/s41590-020-00856-3