Pear peel polyphenols protect against ulcerative colitis <i>via</i> coordinated modulation of gut microbiota and mucosal immunity

Although often regarded as compromising the fruit's sensory quality, pear peel is an edible component that enhances the nutritional and functional value of pears within a whole food diet. Rich in diverse polyphenols with demonstrated bioactivity, the pear peel represents a valuable dietary source of health-promoting compounds; however, its role in ulcerative colitis (UC) remains underexplored. In this study, the protective effect of pear peel polyphenols (PPP) against UC was investigated using both <i>in vitro</i> and <i>in vivo</i> models. PPP markedly suppressed proinflammatory cytokine and enzyme expressions in lipopolysaccharide (LPS) stimulated RAW264.7 macrophages. In dextran sulfate sodium (DSS) induced colitis mice, PPP significantly mitigated UC symptoms, suppressed serum inflammatory cytokine production, and ameliorated histological damage in colon tissues. Moreover, PPP modulated the gut microbiota by reshaping the microbial diversity, enriching beneficial taxa such as <i>Akkermansia</i>, and suppressing proinflammatory taxa including <i>Bacteroides</i>, <i>Enterobacteriaceae</i>, and <i>Parabacteroides</i>. Notably, proteomic analysis further demonstrated that PPP modulated mucosal immunity, particularly by suppressing the levels of immunoglobulin-related molecules (IgM, IgD, and IgA) and attenuating antigen presentation pathways involving major histocompatibility complex (MHC) class II molecules and cluster of differentiation (Cd40) signaling. Altogether, these findings suggest that PPP exerts a protective effect against colitis through the coordinated regulation of gut microbiota and mucosal immunity, highlighting its potential as a functional food ingredient for intestinal health.