Ulcerative colitis(UC)is driven by complex interactions between persistent gut dysbiosis and mucosal barrier compromise.Notoginsenoside R1(NGR1),a bioactive saponin with potent anti-inflammatory properties,and fecal m...Ulcerative colitis(UC)is driven by complex interactions between persistent gut dysbiosis and mucosal barrier compromise.Notoginsenoside R1(NGR1),a bioactive saponin with potent anti-inflammatory properties,and fecal microbiota transplantation(FMT),a direct strategy for ecological restoration,have emerged as promising therapeutic approaches for UC.Here,we investigated the therapeutic efficacy and underlying mechanisms of combining NGR1 with FMT in a dextran sulfate sodium(DSS)-induced colitis model,specifically targeting the“microbiota-metabolite-immune”axis.The combined intervention significantly attenuated histopathological severity and reinforced intestinal barrier integrity.These phenotypic improvements were accompanied by a rebalancing of the immune profile,characterized by the suppression of pro-inflammatory cytokines(IL-6,TNF-α;p<0.01)and the upregulation of anti-inflammatory IL-10.16S rRNA sequencing revealed distinct ecological remodeling where NGR1 monotherapy selectively enriched the mucin-degrading family Muribaculaceae,whereas FMT specifically expanded the abundance of Akkermansia,a keystone genus pivotal for barrier reinforcement.Metabolomic profiling demonstrated that the intervention reprogrammed the colonic metabolome,primarily through restoration of bile acid biosynthesis and histidine metabolic pathways.Notably,a metabolic shift favoring elevated succinyl-CoA and modulated bile acid profiles(e.g.,7-ketolithocholic acid)was significantly correlated with the resolution of inflammation.Collectively,our findings elucidate that NGR1 combined with FMT exerts synergistic therapeutic effects by facilitating a functional restoration of the gut microbiome and metabolic environment,offering a novel,precision-targeted strategy for UC treatment.展开更多
基金supported in part by grants from National Natural Sci-ence Foundation of China(32370092)National Key Research and Development Program of China(2023YFF1103600)Pharmaceutical Scientific Research Project of Gansu Province(2023GSMPA073).
文摘Ulcerative colitis(UC)is driven by complex interactions between persistent gut dysbiosis and mucosal barrier compromise.Notoginsenoside R1(NGR1),a bioactive saponin with potent anti-inflammatory properties,and fecal microbiota transplantation(FMT),a direct strategy for ecological restoration,have emerged as promising therapeutic approaches for UC.Here,we investigated the therapeutic efficacy and underlying mechanisms of combining NGR1 with FMT in a dextran sulfate sodium(DSS)-induced colitis model,specifically targeting the“microbiota-metabolite-immune”axis.The combined intervention significantly attenuated histopathological severity and reinforced intestinal barrier integrity.These phenotypic improvements were accompanied by a rebalancing of the immune profile,characterized by the suppression of pro-inflammatory cytokines(IL-6,TNF-α;p<0.01)and the upregulation of anti-inflammatory IL-10.16S rRNA sequencing revealed distinct ecological remodeling where NGR1 monotherapy selectively enriched the mucin-degrading family Muribaculaceae,whereas FMT specifically expanded the abundance of Akkermansia,a keystone genus pivotal for barrier reinforcement.Metabolomic profiling demonstrated that the intervention reprogrammed the colonic metabolome,primarily through restoration of bile acid biosynthesis and histidine metabolic pathways.Notably,a metabolic shift favoring elevated succinyl-CoA and modulated bile acid profiles(e.g.,7-ketolithocholic acid)was significantly correlated with the resolution of inflammation.Collectively,our findings elucidate that NGR1 combined with FMT exerts synergistic therapeutic effects by facilitating a functional restoration of the gut microbiome and metabolic environment,offering a novel,precision-targeted strategy for UC treatment.
