Background/Objectives: Chemotherapy-induced adverse events significantly impact cancer treatment outcomes and patient quality of life. Emerging evidence suggests that gut microbiota composition may influence individual susceptibility to chemotherapy toxicity. This study investigated associations between gut microbiome alterations and specific chemotherapy-related adverse events in breast cancer patients undergoing cancer treatment.Methods: We conducted a prospective cohort study of 81 breast cancer patients receiving chemotherapy between May 2018 and October 2022. Gut microbiome composition was analyzed using 16S rRNA sequencing across multiple taxonomic levels. Alpha diversity (Chao1 estimator) and beta diversity (PERMANOVA) analyses were performed to assess microbial richness and community structure. Linear discriminant analysis effect size (LEfSe) identified differentially abundant taxa, with Cohen’s d effect sizes calculated with 95% confidence intervals and false discovery rate correction applied for multiple comparisons.Results: Significant microbiome-toxicity associations were identified across 42 taxa (FDR q < 0.05, effect sizes d = −1.60 to +1.67). Severe anemia demonstrated the strongest associations, with large effect size enrichment of Eubacteriaceae (d = 1.38), Anaerofilum (d = 1.42), and Eubacterium (d = 1.38). Severe neutropenia was characterized by depletion of butyrate-producing bacteria, particularly Eubacterium_hallii_group (d = −1.08). Thrombocytopenia showed dramatic depletion of Eubacterium limosum (53-fold reduction, d = −1.60). Hepatotoxicity (ALT elevation) was associated with depletion of Eubacterium_hallii_group (d = −0.99) and Burkholderia-Caballeronia-Paraburkholderia (d = −1.19). Hand-foot syndrome exhibited significantly elevated microbial diversity with depletion of Lachnospiraceae taxa. Most adverse events showed enrichment rather than depletion patterns, with 54.8% of significant associations demonstrating medium to large effect sizes.Conclusions: Specific gut microbiota signatures associated with distinct chemotherapy-related adverse events, suggesting potential microbiome-based biomarkers for toxicity prediction and personalized cancer treatment strategies.
背景/目的：化疗引发的不良事件显著影响癌症治疗效果及患者生活质量。新近证据表明肠道菌群组成可能影响个体对化疗毒性的易感性。本研究探讨了接受癌症治疗的乳腺癌患者肠道微生物组改变与特定化疗相关不良事件之间的关联。 方法：我们对2018年5月至2022年10月期间接受化疗的81例乳腺癌患者进行了前瞻性队列研究。通过16S rRNA测序在多个分类学水平分析肠道微生物组组成。采用α多样性（Chao1指数）和β多样性（PERMANOVA）分析评估微生物丰富度及群落结构。通过线性判别分析效应量（LEfSe）识别差异丰度类群，计算Cohen's d效应量（95%置信区间），并对多重比较进行错误发现率校正。 结果：在42个分类群中发现显著的微生物组-毒性关联（FDR q < 0.05，效应量d = -1.60至+1.67）。重度贫血表现出最强关联性，真杆菌科（d = 1.38）、厌氧丝菌属（d = 1.42）和真杆菌属（d = 1.38）呈现大效应量富集。重度中性粒细胞减少症的特征是产丁酸盐细菌的耗竭，特别是霍氏真杆菌群（d = -1.08）。血小板减少症显示黏液真杆菌的急剧耗竭（降低53倍，d = -1.60）。肝毒性（ALT升高）与霍氏真杆菌群（d = -0.99）及伯克霍尔德菌-卡巴莱罗尼亚-副伯克霍尔德菌复合群（d = -1.19）耗竭相关。手足综合征表现为微生物多样性显著升高伴随毛螺菌科类群耗竭。多数不良事件呈现富集而非耗竭模式，54.8%的显著关联显示中至大效应量。 结论：特定肠道微生物群特征与不同化疗相关不良事件存在关联，提示基于微生物组的生物标志物在毒性预测和个体化癌症治疗策略中具有潜在应用价值。
肿瘤(癌症)患者之家