Metabolomics dataset - Microbial metabolism of L-tyrosine protects against allergic inflammation

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 led to increased levels of p-cresol sulfate (PCS) that protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells, due to an uncoupling of EGFR and 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.肠道微生物组（gut microbiome）的组成由局部生境决定，而局部生境本身又受免疫压力塑造，例如黏膜免疫球蛋白A（IgA）。本研究采用抗体谱受限的小鼠模型，明确了抗体-微生物互作在塑造具有增强L-酪氨酸（L-tyrosine）代谢能力的细菌群落中的关键作用。这一过程使得宿主体内的对甲酚硫酸盐（p-cresol sulfate, PCS）水平升高，而PCS可保护宿主抵御过敏性气道炎症。由于表皮生长因子受体（EGFR）与Toll样受体4（TLR4）的信号通路发生解偶联，PCS可选择性抑制气道上皮细胞产生趋化因子配体20（CCL20）。综上，本研究数据揭示了一条由肠道微生物衍生的代谢物通路，该通路可远端作用于气道上皮，从而减轻过敏性气道应答——这类应答正是哮喘的核心发病基础。