An olsalazine nanoneedle-embedded inulin hydrogel reshapes intestinal homeostasis in inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic and refractory condition characterized by disrupted epithelial barrier,dysregulated immune balance,and altered gut microbiota.Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD.Herein,we developed a combination of olsalazine(Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation.The Olsa-derived nanoneedles exhibited reactive oxygen species scavenging ability and anti-inflammatory effects in lipopolysaccharide-simulated macrophages.The composite of nanoneedles and inulin gel(Cu2(Olsa)/Gel)displayed a macroporous structure,improved bio-adhesion,and enhanced colon retention after oral administration.Mechanistically,the composite effectively downregulated pro-inflammatory cytokine levels and promoted epithelial barrier repair through anti-inflammatory and antioxidant therapies,resulting in significant alleviation of colitis in three animal models of IBD.Furthermore,analysis of gut microbiota revealed that Cu2(Olsa)/Gel treatment increased the diversity of intestinal microflora and decreased the relative abundance of pathogenic bacteria such as Proteobacteria.Overall,this study provides a self-delivering nanodrug and dietary fiber hydrogel composite for IBD therapy,offering an efficient approach to restore intestinal homeostasis.