Lentinus β-Glucan Binds to Macrophages and Inhibits Colitis in a Molecular Weight-Dependent Manner

Colitis, a globally prevalent chronic gastrointestinal disorder, remains a key challenge for developing safe and effective therapies. Polysaccharide dietary fiber supplementation is a promising preventive measure. Notably, molecular weight (MW) critically determines the bioactivities of polysaccharides. Herein, we investigate the influence of Lentinus β-glucan (LBG) of distinct MWs on colitis. In our findings, LBG bound to the dectin-1 receptor on LPS-stimulated RAW264.7 macrophages and suppressed inflammatory factor secretion; orally administered LBG interacted with intestinal macrophages and alleviated colitis by reducing oxidative stress and proinflammatory factors, increasing colon length from 5.7 to 8.7 cm, restoring tissue damage, and reconstructing the intestinal mucosal barrier through upregulation of ZO-1 and Claudin-1. All these findings reversely depended on weight-average molecular weight ( M w ) within 1410–2560 kDa, and LBG-60 with an M w of 1410 kDa showed the optimal therapeutic effect, possibly associated with its binding to macrophages. This study provides evidence for LBG with desired MW as a dietary fiber for colitis prevention.