Influenza virus infection induced severe pneumonia results in destructive lung pathological damage. A timely and proper tissue repair is essential to improve outcomes. Through shotgun metagenomic sequencing, we profiled specific gut microbial structures in severe influenza patients with depleted Faecalibacterium. prausnitzii. Combined with metabolomics, we identified Faecalibacterium. prausnitzii and its key metabolite butyrate play protective roles against influenza induced acute lung injury. Single-cell RNA sequencing results depicted immune response properties and revealed a differentiation of CD4+T cell into reparative phenotype with increased IL-22 production in lung CD4+T cell by butyrate. Mechanistically, butyrate-elicited IL-22 production is in association with monounsaturated fatty acid biosynthesis via histone acetylation-modified NR4A1 SCD1 axis. The accumulated monounsaturated fatty acid improved mitochondrial activities, which is a critical cellular process involved in IL-22 production. In an IL-22 knockout mouse model, we ascertained the non-redundant role of IL-22 in this gut-lung axis. Our findings highlight a novel regulatory role of intestinal commensal-derived butyrate in maintaining epithelial integrity through CD4+T cell intrinsic lipid metabolic remodeling and provide a promising therapeutic potential of Faecalibacterium. prausnitzii in influenza.
茅浙英(Mao zheying) (Thu,) studied this question.
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