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 ho...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.展开更多
基金supported by the National Natural Science Foundation of China(51903172,52073216)the Sichuan Science and Technology Program(2022NSFSC1939).
文摘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.
