Microbiome-host genetic association.

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）仍是全球范围内女性癌症相关发病与死亡的主要诱因。传统治疗手段涵盖手术、放射治疗、激素治疗与化学治疗，但此类方案常因患者应答存在异质性且伴随不良反应而面临诸多挑战。本研究针对接受乳腺癌化疗的受试女性（化疗期间组，During Treatment-DT）与无癌对照组（Cancer-Free Controls, CFC）的肠道菌群多样性、群落组成及通路分析之间的关联展开探究。研究采用16S rRNA扩增子测序技术，对α多样性与β多样性进行评估。结果显示，化疗期间组与无癌对照组的菌群组成存在显著差异，且厚壁菌门（Firmicutes）在两组中均呈高丰度状态。本研究在门与属水平开展核心菌群及相关性分析，筛选出具有统计学意义的菌群。具体而言，通过统计学与机器学习方法分析发现，假单胞菌属（Pseudomonas）、阿克曼氏菌属（Akkermansia）等菌属的丰度显著降低，而瘤胃球菌属（Ruminococcus）、别样杆菌属（Allistipes）的丰度则显著升高。本研究基于KEGG正交（KEGG Orthology, KO）丰度开展疾病关联分析，发现菌群与自闭症谱系障碍、艰难梭菌感染、慢性肾病及多发性硬化等病症存在关联。两组富集的关键KEGG通路包括双组分调控系统、酪氨酸代谢途径及磷酸戊糖途径。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。本研究结果凸显了该发现对于优化治疗结局与推进个性化医疗的潜在应用价值。