Integrated analysis of microbiota and gut microbial metabolites in blood for breast cancer

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Abstract
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. IMPORTANCE: Our 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.

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