Multi-omics analysis of the alleviating effect of pectic oligosaccharides (POS) on DSS-induced colitis through the increase of unsaturated fatty acids

Ulcerative colitis (UC) represents a persistent form of intestinal inflammation, typically defined by localized rectal and colonic injury. The pathogenesis of this condition involves significant disturbances in the enteric microbial community alongside systemic immunological imbalances. Our previous study has demonstrated the anti-colitis effect of enzymatic pectin oligosaccharides (POS). This study further explored the underlying mechanism by modulating gut microbiota composition and metabolites in a dextran sulfate sodium (DSS)-induced mouse colitis model via multi-omics analysis. Our results indicated that POS alleviates colitis symptoms by reshaping the gut microbiota, facilitating the production of gut microbial-produced unsaturated fatty acids (UFA), as analyzed by metagenomics and non-targeted metabolomics. Meanwhile, transcriptomic and Spearman correlation analyses of intestinal tissues support that UFAs produced by POS regulate the expression of host genes related to tissue regeneration and immune infiltration (e.g., Areg , Cd6 ), restore gut mucosal homeostasis, and regulate cytokine secretion. These findings validate the key role of the gut microbiota – UFA - host axis, offering multi - omics evidence for the potential application of POS in the UC therapy. • POS alleviates colitis by reshaping gut microbiota and promoting UFA production. • Microbial UFAs restore intestinal mucosal homeostasis and regulate cytokines. • Gut microbiota-UFA-host axis provides multi-omics evidence for POS as a potential UC therapeutic agent.