L-精氨酸缓解肠道炎症的作用及机制OA

Gut microbiota-derived metabolites play critical roles in maintaining intestinal homeostasis,yet the specific effector molecules and their anti-inflammatory mechanisms remain unclear.Our previous studies showed that two commensal intestinal bacterial strains,Dubosiella newyorkensis(Dub)and Blautia coccoides(BC),significantly alleviated dextran sodium sulfate(DSS)-induced colitis in mice.Using targeted metabolomics,we identified L-arginine(Arg)as a common metabolite significantly upregulated by both strains.To investigate whether Arg directly protects the intestinal epithelium,we employed a DSS-induced colitis mouse model fed a basal diet containing 1%Arg or a 3%Arg-supplemented diet,and further used intestinal organoids derived from germ-free mice,pigs,and humans to evaluate the direct regulatory effects of Arg on intestinal epithelial cells.Compared with the 1%Arg group,the 3%Arg group exhibited reduced body weight loss,increased colon length,ameliorated histopathological damage,elevated expression of the intestinal stem cell marker—leucine-rich repeat-containing G-protein coupled receptor 5(LGR5)and proliferation marker Ki67,restored expression of occludin and goblet cell marker mucin 2(Muc2),and decreased infiltration of interleukin-6(IL-6)-positive macrophages.In intestinal organoids derived from germ-free mice,pigs,and humans,Arg treatment significantly promoted organoid growth,dose-dependently upregulated Lgr5(mouse)and LGR5(pig and human)mRNA levels,and protected organoids from tumor necrosis factor α(TNFα)/interferon γ(IFNγ)-induced inflammatory injury by maintaining their mRNA levels.These results demonstrate that Arg directly acts on intestinal epithelial cells to enhance stem cell properties,restore barrier function,and suppress inflammatory responses,thereby alleviating intestinal inflammation,with this effect being highly conserved in intestinal organoid models derived from mice,pigs,and humans.This study reveals the role and mechanism of Arg,a common bacterial metabolite,in alleviating intestinal inflammation,providing a theoretical basis for its translational application in maintaining piglet intestinal health and preventing intestinal inflammatory disorders.