Therapeutic potential of Ficus pumila L. in chronic obstructive pulmonary disease through modulation of the gut microbiota-SCFA-lung signaling pathway

Ficus pumila L. has been reported to alleviate pulmonary inflammation, its impact on chronic obstructive pulmonary disease (COPD) pathobiology-specifically via modulation of the gut-lung signaling pathway-has yet to be mechanistically defined. This study investigated how Ficus pumila L. polysaccharides (FP-P) and aqueous extracts (FP-E) remodel the gut microbiome-SCFA network and restore microbial metabolic function in a cigarette smoke–induced COPD mouse model. Microbiota composition was profiled by high-resolution 16S rRNA amplicon sequence variant (ASV) analysis, with concomitant quantification of caecal SCFA using targeted gas chromatography–mass spectrometry (GC–MS) and inference of metagenome function by PICRUSt2. Results demonstrated that FP-P and FP-E alleviated pulmonary pathology, reduced inflammatory cytokine secretion, and significantly restored gut microbiota α-diversity in COPD mice. At the family level, FP-P selectively expanded SCFA-producing Clostridiaceae , and Staphylococcaceae , whereas it contracted pro-inflammatory Helicobacteraceae and Campylobacteraceae . Caecal total SCFA concentration increased by 41.90 %, driven primarily by elevations in butyrate (+23.41 %) and propionate (+45.45 %), without significant changes in acetate. PICRUSt2-inferred metagenomes showed up-regulation of butanoate biosynthesis (PWY-5677), metabolism of cofactors and amino acid (P162-PWY and NAD-BIOSYNTHESIS-II), and carbohydrate degradation (P341-PWY), all of which underpin SCFA production. These functional shifts were accompanied by increased abundance of microbial genes encoding ribosomal proteins and ATP-binding cassette transporters, indicating barrier reinforcement. Collectively, FP-P and FP-E mitigate CS-induced COPD pathology through a gut microbiota-SCFA-lung signaling signaling pathway, highlighting the gut-to-lung communication within the broader gut-lung axis. These findings establish a mechanistic link between microbial metabolism and pulmonary inflammation while acknowledging that the reverse lung-to-gut feedback remains to be elucidated. Future studies will investigate this bidirectional crosstalk and the receptor-mediated signaling of SCFAs in lung tissue.