Rosa roxburghii Fermentation Broths Attenuate Bleomycin-Induced Pulmonary Fibrosis by Activating the Nrf2/HO-1/NQO1 Signaling Pathway and Modulating Gut Microbiota

Pulmonary fibrosis (PF) is a chronic and progressive lung disease, and oxidative stress plays a critical role in its pathogenesis. Rosa roxburghii Tratt, known for its anti-inflammatory and antioxidant properties, has been shown to alleviate fibrosis. This study aimed to explore whether two Rosa roxburghii fermentation broths (RRFBs) (with different proportions) could attenuate bleomycin (BLM)-induced PF in mice and to elucidate the molecular mechanisms. The results revealed that RRFBs reduced structural lung damage, collagen deposition, and lung inflammation. RRFBs also suppressed fibrotic markers (Collagen I, Vimentin, and alpha-SMA) while enhancing epithelial marker E-cadherin expression. Additionally, RRFBs alleviated BLM-induced oxidative stress and apoptosis by activating the Nrf2/HO-1/NQO1 signaling pathway and facilitating Nrf2 nuclear translocation. Furthermore, RRFBs attenuated the BLM-induced changes in the gut microbiota; in particular, they decreased the abundance of the pathogenic bacterium Proteus and increased the abundance of the probiotics Ileibacterium and Dubosiella. Spearman correlation analysis revealed a strong association between oxidative stress inhibition and gut microbiota composition. These results indicated that RRFBs could exert lung-protective effects by inhibiting oxidative stress and alleviating intestinal disturbances.