PDF(Pubmed)
Abstract：
Microbiota are known to modulate the host response to influenza infection, but the mechanisms remain largely unknown. Gut metabolites are the key mediators through which gut microbes play anti-influenza effect. Transferring fecal metabolites from mice with high influenza resistance into antibiotic-treated recipient mice conferred resistance to influenza infections. By comparing the metabolites of different individuals with high or low influenza resistance, we identified and validated N-acetyl-D-glucosamine (GlcNAc) and adenosine showed strong positive correlations with influenza resistance and exerted anti-influenza effects in vivo or in vitro, respectively. Especially, GlcNAc mediated the anti-influenza effect by increasing the proportion and activity of NK cells. Several gut microbes, including Clostridium sp., Phocaeicola sartorii, and Akkermansia muciniphila, were positively correlated with influenza resistance, and can upregulate the level of GlcNAc in the mouse gut by exogenous supplementation. Subsequent studies confirmed that administering a combination of the three bacteria to mice via gavage resulted in similar modulation of NK cell responses as observed with GlcNAc. This study demonstrates that gut microbe-produced GlcNAc protects the host against influenza by regulating NK cells, facilitating the elucidation of the action mechanism of gut microbes mediating host influenza resistance.
摘要：
已知微生物区系可以调节宿主对流感感染的反应，但机制在很大程度上仍然未知。肠道代谢产物是肠道微生物发挥抗流感作用的关键介质。将具有高流感抗性的小鼠的粪便代谢物转移到抗生素处理的受体小鼠中赋予对流感感染的抗性。通过比较具有高或低流感抗性的不同个体的代谢物，我们鉴定并验证了N-乙酰-D-葡糖胺（GlcNAc）和腺苷与流感耐药性呈强正相关，并在体内或体外发挥抗流感作用，分别。尤其是,GlcNAc通过增加NK细胞的比例和活性来介导抗流感作用。几种肠道微生物，包括梭菌属。,Phocaeicolasartorii,和阿克曼西亚粘虫，与流感抗性呈正相关，并且可以通过外源性补充来上调小鼠肠道中GlcNAc的水平。随后的研究证实,通过管饲法向小鼠施用三种细菌的组合导致与用GlcNAc观察到的类似的NK细胞应答调节。这项研究表明，肠道微生物产生的GlcNAc通过调节NK细胞保护宿主免受流感，有助于阐明肠道微生物介导宿主流感抗性的作用机制。
