Integrated insights into gut microbiota and metabolomic landscape in breast cancer patients undergoing adjuvant endocrine therapy

作者：Taha Majid Mahmood Sheikh, Fen Yao, Zhenyan Liu, Muhammad Shafiq, Jilong Wu, Areeba Khalid, Qingdong Xie, Xiaoyang Jiao, Wanjie Shen · 发表于：mSystems · 年份：2025 · DOI：10.1128/msystems.00879-25 · 被引用次数：9 · 研究领域：Gut microbiota and health、Metabolomics and Mass Spectrometry Studies、Diet and metabolism studies

ABSTRACT Gut microbiota and systemic metabolites are critical for breast cancer progression and therapeutic response. This study investigated gut microbiota and metabolic profiles of breast cancer patients before and after adjuvant endocrine therapy (AET). Using 16S rRNA sequencing and untargeted metabolomics, we identified significant disruptions in microbial diversity and metabolic pathways. Alpha diversity was reduced in pre-AET patients, with partial restoration observed post-AET. Key genera, such as Bifidobacterium and Coprococcus , were enriched in pre-AET patients, whereas Proteus and Methylobacterium were enriched in post-AET patients. Metabolomic analysis revealed significant reductions in the levels of vitamin B6 metabolites in both the pre-AET and post-AET groups compared to those in the healthy control (HC) group, indicating potential nutrient deficiencies or metabolic stress. Elevated cholesterol and estrogen metabolite levels in pre-AET patients reflect dysregulated lipid and hormone metabolism, with post-AET decreases in estrogen metabolites, confirming therapeutic efficacy. Correlation analysis revealed that Klebsiella_724518 was positively correlated with estrogen and vitamin B6 metabolites, whereas Proteus , Methylobacterium , Treponema_D , and Holdemanella were negatively correlated with cholesterol. Receiver operating characteristic (ROC) curve analysis identified estriol (area under the curve [AUC] = 1.000) as a strong diagnostic biomarker for distinguish...