Hemp seed mitigates colonic inflammation through macrophage polarization and microbiota-barrier axis restoration

Hemp seed, historically considered a byproduct of the hemp fiber industry, has gained increasing attention for its nutritional and functional properties. Recent advances in hemp seed research have elucidated its benefits for gut health; however, its impact on colitis remains unclear. In this study, we demonstrate that hemp seed consumption reduced colonic inflammation and mitigated tissue injury in an experimental colitis mouse model. Notably, hemp seed reduced macrophage infiltration and promoted a phenotypic shift from pro-inflammatory M1 to anti-inflammatory M2 macrophages. It also enhanced intestinal barrier function by restoring goblet cells, upregulating tight junction proteins, and reducing systemic lipopolysaccharide translocation. Furthermore, hemp seed optimized gut microbiota composition by enriching beneficial taxa, particularly <i>Bifidobacterium</i>, while suppressing colitis-associated genera. Collectively, these findings indicate that hemp seed, as a whole-food dietary approach, confers protection against colitis by modulating immune responses, preserving barrier integrity, and reshaping gut microbiome. These results underscore the potential of hemp seed as a sustainable nutritional strategy for promoting gut health.