Structural characterization and medium-chain acyl-coenzyme a dehydrogenase-mediated anti-inflammatory mechanism of a Hulless barley Monascus polysaccharide in ulcerative colitis.

Polysaccharides isolated from Hulless barley Monascus (HBM) have demonstrated remarkable potential in modulating gut microbiota and reinforcing intestinal barrier integrity. However, their precise therapeutic efficacy and mechanisms against ulcerative colitis (UC) remain unclear. In this study, we purified and structurally characterized a novel HBM polysaccharide with a molecular weight of 24.67 kDa, composed primarily of glucose, xylose, and rhamnose. In vitro experiments revealed that HBM facilitated a phenotypic switch in macrophages from a pro-inflammatory M1 state to an anti-inflammatory M2 state by enhancing fatty acid oxidation (FAO), predominantly via upregulation of the ACADM enzyme. In vivo, oral administration of HBM significantly alleviated DSS-induced UC in mice by promoting ACADM-mediated FAO, restoring immune balance. Integrated plasma metabolomics and spatial mass spectrometry imaging analyses identified that the differential metabolites were chiefly associated with fatty acid elongation and degradation pathways. Collectively, our findings demonstrate that HBM exerts protective effects against UC through ACADM-dependent FAO activation, highlighting its potential as a functional dietary supplement for UC management.