Department of Epidemiology and Biostatistics, Key Laboratory of Molecular Cancer Epidemiology, Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China.
mSystems. 2024 Nov 19;9(11):e0064324. doi: 10.1128/msystems.00643-24. Epub 2024 Oct 18.
Gut microbiota and associated metabolites have been linked to breast carcinogenesis. Evidences demonstrate blood microbiota primarily originates from the gut and may act as a biomarker for breast cancer. We aimed to characterize the microbiota-gut microbial metabolites cross-talk in blood and develop a composite diagnostic panel for breast cancer. We performed 16S rRNA gene sequencing and metabolomics profiling on blood samples from 107 breast cancer cases and 107 age-paired controls. We found that the alpha diversity of the blood microbiota was decreased in breast cancer compared to controls. There were significantly different profiles of microbiota and gut microbial metabolites in blood between these two groups, with nine bacterial genera and four gut microbial metabolites increased in patients, while thirty-nine bacterial genera and two gut microbial metabolites increased in controls. Some breast cancer-associated gut microbial metabolites were linked to differential blood microbiota, and a composite microbiota-metabolite diagnostic panel was further developed with an area under the curve of 0.963 for breast cancer. This study underscored the pivotal role of microbiota and gut microbial metabolites in blood and their interactions for breast carcinogenesis, as well as the potential of a composite diagnostic panel as a non-invasive biomarker for breast cancer.IMPORTANCEOur integrated analysis demonstrated altered profiles of microbiota and gut microbial metabolites in blood for breast cancer patients. The extensive correlation between microbiota and gut microbial metabolites in blood assisted the understanding of the pathogenesis of breast cancer. The good performance of a composite microbiota-gut microbial metabolites panel in blood suggested a non-invasive approach for breast cancer detection and a novel strategy for better diagnosis and prevention of breast cancer in the future.
肠道微生物群及其相关代谢物与乳腺癌的发生有关。有证据表明，血液中的微生物群主要来源于肠道，可作为乳腺癌的生物标志物。我们旨在描述血液微生物群-肠道微生物代谢物的相互作用，并开发用于乳腺癌的综合诊断面板。我们对 107 例乳腺癌病例和 107 例年龄匹配的对照者的血液样本进行了 16S rRNA 基因测序和代谢组学分析。我们发现，与对照组相比，乳腺癌患者血液中的微生物群 alpha 多样性降低。这两组之间血液中的微生物群和肠道微生物代谢物的特征明显不同，患者中有 9 个细菌属和 4 种肠道微生物代谢物增加，而对照组中有 39 个细菌属和 2 种肠道微生物代谢物增加。一些与乳腺癌相关的肠道微生物代谢物与血液中不同的微生物群有关，并且进一步开发了一个具有 0.963 曲线下面积的微生物群-代谢物综合诊断面板用于乳腺癌。本研究强调了血液中微生物群和肠道微生物代谢物在乳腺癌发生中的关键作用及其相互作用，以及作为乳腺癌非侵入性生物标志物的复合诊断面板的潜力。
我们的综合分析表明，乳腺癌患者血液中的微生物群和肠道微生物代谢物的特征发生了改变。血液中微生物群和肠道微生物代谢物之间的广泛相关性有助于了解乳腺癌的发病机制。血液中复合微生物群-肠道微生物代谢物组学面板的良好性能表明，这是一种用于乳腺癌检测的非侵入性方法，也是未来更好地诊断和预防乳腺癌的新策略。
