摘要目的:评估局部进展期直肠癌患者肠道菌群代谢物在预测新辅助放化疗联合免疫治疗疗效中的潜在价值。方法:前瞻性收集2021年10月—2022年8月在首都医科大学附属北京友谊医院行全直肠系膜切除术并经病理诊断确诊的32例局部进展期中低位、单发直肠癌患者的病历资料，其中男性18例(56.25%)，女性14例(43.75%)，年龄37～79岁，平均年龄(61.69±8.73)岁。根据肿瘤退缩分级(TRG)评估术后病理学缓解，将患者分为有疗效组(ypT 0N 0， n＝14)和无疗效组(非ypT 0N 0， n＝18)。收集患者新辅助放化疗联合免疫治疗前的粪便；采用高效液相色谱-串联质谱技术分析代谢物并富集通路；基于差异代谢物构建了随机森林模型。采用R4.4.1和SPSS26.0软件进行统计分析。 结果:通过非靶向代谢组学检测分析发现2′-脱氧肌酐、芍药内酯苷等富集在有疗效组，而山梨醇单油酸酯、2-(甲酰氨基)苯甲酸、12-羟基月桂酸等富集在无疗效组( P<0.05)；花生四烯酸代谢、色氨酸代谢等通路被富集，随机森林模型AUC值为0.976。 结论:术后病理学是否完全缓解的直肠癌患者在新辅助放化疗联合免疫治疗前肠道菌群代谢物质存在差异，所识别的差异代谢物有望成为疗效预测的潜在生物标志物。

abstractsObjective:To evaluate the potential value of gut microbiota metabolites in predicting the efficacy of neoadjuvant chemoradiotherapy combined with immunotherapy in patients with locally advanced rectal cancer.Methods:Prospectively collected case data from 32 patients with locally advanced rectal patients, who underwent total mesorectal excision at Beijing Friendship Hospital, Capital Medical University, between October 2021 and August 2022. Among these patients, 18 (56.25%) were male and 14 (43.75%) were female, with ages ranging from 37 to 79 years and a mean age of (61.69±8.73) years. Postoperative pathological response was evaluated using the Tumor Regression Grade (TRG), dividing the patients into two groups: an efficacious group (ypT 0N 0, n=14) and a non-efficacious group (non-ypT 0N 0, n=18). Stools from 14 patients in the efficacious group and 18 patients in the non-efficacious group, who had experienced neoadjuvant chemoradiotherapy combined with immunotherapy, were collected before treatment. Metabolites were analyzed using high-performance liquid chromatography-tandem mass spectrometry, and pathway enrichment analysis was performed. A random forest model was constructed based on the differential metabolites. The data were analyzed by using R4.1.1 and 26.0 software. Results:Through untargeted metabolomics analysis, 2′-Deoxyinosine and albiflorin were enriched in the responders, while Sorbitan monooleate, 2-(Formylamino) Benzoic Acid, and 12-Hydroxydodecanoic acid were enriched in the non-responders ( P<0.05); Arachidonic acid metabolism and tryptophan metabolism were enriched, and the AUC for the model was 0.976. Conclusions:Rectal cancer patients with or without complete postoperative pathological remission exhibit differences in the metabolites of their intestinal microbiome prior to undergoing neoadjuvant chemoradiotherapy combined with immunotherapy. The identified differential metabolites have the potential to serve as predictive biomarkers for treatment efficacy.