Roles of gut microbiome-associated metabolites in pulmonary fibrosis by integrated analysis

Lung diseases often coincide with imbalances in gut microbiota, but the role of gut microbiota in pulmonary fibrosis (PF) remains unclear. This study investigates the impact of gut microbiota and their metabolites on PF. Serum and lung tissues of normal, bleomycin (BLM)- and silica-induced mice showed significant differences in gut microbiota. L-Tryptophan was upregulated within pulmonary tissue and serum metabolites both in the BLM and Silica groups. The dominant gut microbiota associated with L-tryptophan metabolism included Lachnospiraceae_NK4A136_Group, Allobaculum, Alistipes, and Candidatus_Saccharimonas. L-Tryptophan promoted BLM- and silica-induced pathological damage in PF mice. L-Tryptophan promoted TGF-β1-induced EMT and fibroblast activation in vitro via activating the mTOR/S6 pathway. In conclusion, PF mice exhibited alterations in gut microbiota and serum and lung tissue metabolites. L-Tryptophan level was associated with changes in gut microbiota, and L-tryptophan promoted PF progression in both in vivo and in vitro models, potentially through activation of the mTOR/S6 pathway.