Cyclophosphamide(CTX),a widely used chemotherapeutic agent,frequently causes severe immunosuppression that limits its clinical application.Xylooligosaccharides(XOS)are well-recognized prebiotics that selectively modul...Cyclophosphamide(CTX),a widely used chemotherapeutic agent,frequently causes severe immunosuppression that limits its clinical application.Xylooligosaccharides(XOS)are well-recognized prebiotics that selectively modulate gut microbiota and enhance short-chain fatty acids(SCFAs)production.However,their protective effects against CTX-induced immunosuppression remain unknown.This study demonstrates that XOS intervention effectively attenuates CTX-induced immunosuppression in mice,restoring body weight,reversing thymic and splenic atrophy,and normalizing hematological parameters including leukocyte counts,immunoglobulin levels,and complement protein concentrations.Microbiome analysis revealed XOS-mediated restoration of microbial diversity and selective enrichment of beneficial taxa like Limosilactobacillus and Gordonibacter.Metabolomic profiling demonstrated XOS-induced increases in key SCFAs(acetic,propionic,and valeric acids)and immunoregulatory metabolites(thymine and Gly-Leu).Integrative multi-omics analysis revealed associations among Lactobacillus/Lachnospiraceae_NK4A136_group abundance,SCFAs levels,and immune markers.These findings suggest a potential link between XOS-induced microbial changes,metabolic shifts,and immune modulation.Collectively,this study provides correlative evidence supporting the role of XOS as a microbiota-targeted candidate for ameliorating chemotherapy-induced immunosuppression,highlighting a potential strategy to improve the safety and efficacy of CTX treatment.展开更多
基金supported by the Postdoctoral Fellowship Program of CPSF(GZC20230985)Jiangsu Specially-Appointed Professor program.All authors have read and approved the final manuscript.
文摘Cyclophosphamide(CTX),a widely used chemotherapeutic agent,frequently causes severe immunosuppression that limits its clinical application.Xylooligosaccharides(XOS)are well-recognized prebiotics that selectively modulate gut microbiota and enhance short-chain fatty acids(SCFAs)production.However,their protective effects against CTX-induced immunosuppression remain unknown.This study demonstrates that XOS intervention effectively attenuates CTX-induced immunosuppression in mice,restoring body weight,reversing thymic and splenic atrophy,and normalizing hematological parameters including leukocyte counts,immunoglobulin levels,and complement protein concentrations.Microbiome analysis revealed XOS-mediated restoration of microbial diversity and selective enrichment of beneficial taxa like Limosilactobacillus and Gordonibacter.Metabolomic profiling demonstrated XOS-induced increases in key SCFAs(acetic,propionic,and valeric acids)and immunoregulatory metabolites(thymine and Gly-Leu).Integrative multi-omics analysis revealed associations among Lactobacillus/Lachnospiraceae_NK4A136_group abundance,SCFAs levels,and immune markers.These findings suggest a potential link between XOS-induced microbial changes,metabolic shifts,and immune modulation.Collectively,this study provides correlative evidence supporting the role of XOS as a microbiota-targeted candidate for ameliorating chemotherapy-induced immunosuppression,highlighting a potential strategy to improve the safety and efficacy of CTX treatment.
