Summary description of the samples.

Breast cancer (BC) continues to be a major cause of cancer-related illness and death among women worldwide. Traditional treatments include surgery, radiation, hormone therapy, and chemotherapy, but these approaches often face challenges due to variability in patient response and adverse effects. This study investigated the relationship between gut microbiome diversity, community composition, and pathway analysis in women undergoing chemotherapy for BC (During Treatment-DT) compared to cancer-free controls (CFC). Using 16S rRNA amplicon sequencing, the study assessed alpha and beta diversity. Results showed differences in microbiome composition between DT and CFC samples, with Firmicutes being highly abundant in both groups. Core microbiome and correlation analysis at the phylum and genus levels identified significant microbiota. Specifically, the abundance of genera such as Pseudomonas and Akkermansia decreased, while Ruminococcus and Allistipes increased, as determined by statistical and machine learning approaches. Disease associations were examined based on KO abundance, identifying links to conditions such as autism spectrum disorder, Clostridium difficile infection, chronic kidney disease, and multiple sclerosis. Key KEGG pathways enriched in DT and CFC groups included the two-component system, tyrosine metabolism, and the pentose phosphate pathway. Conversely, dysbiosis or the presence of pathogenic bacteria (Ruminococcus) associated with the SOX8 gene could lead to chemoresistance, altered metabolic pathways, and increased toxicity. These findings underscore the potential implications for treatment outcomes and personalized medicine.乳腺癌（Breast Cancer, BC）仍是全球范围内导致女性癌症相关疾病与死亡的主要病因之一。传统治疗手段涵盖手术、放疗、激素治疗与化学治疗，但此类方案常因患者应答异质性及不良反应面临诸多局限。本研究针对接受乳腺癌化疗的受试者（化疗期间组，During Treatment-DT, DT）与癌症无病史对照人群（Cancer-Free Controls, CFC），探究了肠道微生物组多样性、群落组成及代谢通路特征的组间关联。本研究采用16S rRNA扩增子测序技术，对α多样性与β多样性进行了评估。研究结果显示，DT组与CFC组样本的微生物组组成存在显著差异，且厚壁菌门（Firmicutes）在两组中均呈高丰度状态。在门与属水平开展的核心微生物组分析与相关性分析，筛选出了具有统计学显著性的微生物类群。具体而言，经统计学与机器学习方法验证发现，假单胞菌属（Pseudomonas）、阿克曼氏菌属（Akkermansia）等菌属的丰度呈下降趋势，而瘤胃球菌属（Ruminococcus）、Allistipes菌属的丰度则有所上升。基于KEGG直系同源基因（KEGG Orthology, KO）丰度开展的疾病关联分析，揭示了该微生物组与自闭症谱系障碍、艰难梭菌感染、慢性肾病及多发性硬化等病症的关联。DT组与CFC组中富集的关键KEGG通路涵盖双组分系统、酪氨酸代谢以及磷酸戊糖途径。反之，与SOX8基因相关的菌群失调或致病性细菌（瘤胃球菌属，Ruminococcus）的存在，可能引发化疗耐药、代谢通路异常及毒性增强等问题。上述研究结果凸显了该发现对优化治疗结局与推动个性化医疗的潜在应用价值。