Membrane glycoprotein is the most abundant protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but its role in coronavirus disease 2019 (COVID-19) has not been fully characterized. Mice intranasally inoculated with membrane glycoprotein substantially increased the interleukin (IL)-6, a hallmark of the cytokine storm, in bronchoalveolar lavage fluid (BALF), compared to mice inoculated with green fluorescent protein (GFP). The high level of IL-6 induced by membrane glycoprotein was significantly diminished in phosphodiesterase 4 (PDE4B) knockout mice, demonstrating the essential role of PDE4B in IL-6 signaling. Mycelium fermentation of Lactobacillus rhamnosus (L. rhamnosus) EH8 strain yielded butyric acid, which can down-regulate the PDE4B expression and IL-6 secretion in macrophages. Feeding mice with mycelia increased the relative abundance of commensal L. rhamnosus. Two-week supplementation of mice with L. rhamnosus plus mycelia considerably decreased membrane glycoprotein-induced PDE4B expression and IL-6 secretion. The probiotic activity of L. rhamnosus plus mycelia against membrane glycoprotein was abolished in mice treated with GLPG-0974, an antagonist of free fatty acid receptor 2 (Ffar2). Activation of Ffar2 in the gut-lung axis for down-regulation of the PDE4B-IL-6 signalling may provide targets for development of modalities including probiotics for treatment of the cytokine storm in COVID-19.

膜糖蛋白是严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 中最丰富的蛋白质，但其在 2019 冠状病毒病 (COVID-19) 中的作用尚未得到充分表征。与接种绿色荧光蛋白 (GFP) 的小鼠相比，鼻内接种膜糖蛋白的小鼠显着增加了支气管肺泡灌洗液 (BALF) 中白细胞介素 (IL)-6，这是细胞因子风暴的标志。膜糖蛋白诱导的高水平 IL-6 在磷酸二​​酯酶 4 (PDE4B) 敲除小鼠中显着降低，证明 PDE4B 在 IL-6 信号传导中的重要作用。鼠李糖乳杆菌（L. rhamnosus）的菌丝体发酵) EH8菌株产生丁酸，可以下调巨噬细胞中PDE4B的表达和IL-6的分泌。用菌丝喂养小鼠增加了共生鼠李糖乳杆菌的相对丰度。用鼠李糖乳杆菌加菌丝体补充小鼠两周可显着降低膜糖蛋白诱导的 PDE4B 表达和 IL-6 分泌。在用游离脂肪酸受体 2 (Ffar2) 拮抗剂 GLPG-0974 处理的小鼠中，鼠李糖乳杆菌加菌丝体对膜糖蛋白的益生菌活性被消除。激活肠肺轴中的 Ffar2 以下调 PDE4B-IL-6 信号传导可能为开发包括益生菌在内的治疗 COVID-19 细胞因子风暴的方式提供目标。