Abstract

Abstract The human body harbors ten times more bacterial cells than human cells - a stunning figure that suggests a likely dynamic between our bodies and the bacteria we carry, both in health and disease. In this study, we characterized and compared the gut and oral microbiota from women with invasive breast cancer, women with ductal carcinoma in situ (DCIS), and healthy women. Samples were collected prior to any systemic therapy to avoid therapy-associated effects on the microbiomes studied. Kits for collecting oral and stool swab samples were distributed to patients for self-collection. DNA was isolated from these samples and bacterial 16S rRNA was PCR amplified and sequenced. Based on the sequencing results, bacterial taxa present in the samples were enumerated. The gut microbiota of women with breast cancer demonstrated significantly lower alpha-diversity compared to the gut microbiomes of healthy women. In contrast, there was no difference in gut microbiota alpha-diversity of women with DCIS compared to healthy women. There were no differences in alpha-diversity of the oral microbiota between any of the cohorts. Discriminant analysis of principal components (DAPC) at the genus level of both the gut and oral microbiota demonstrated distinct clustering of the DCIS, breast cancer, and healthy cohorts. LEfSe analyses were performed to detect differences in relative abundance of bacterial taxa across the gut and oral samples. The genus Bacteroides was significantly enriched in breast cancer compared to healthy samples, as were the related taxa Bacteroidetes (phylum), Bacteroidia (class), Bacteroidales (order), and Bacteroidaceae (family). The genera Fusicatenibacter and Butyrivibrio, both from the phylum Firmicutes, class Clostridia, order Clostridiales, family Lachnospiraceae, were more abundant in the healthy cohort. Only 2 genera, Fusicatenibacter and Clostridium were differentially abundant between the DCIS and healthy gut samples, both being enriched in the healthy samples. Numerous taxa in the oral microbiota were found to be differentially abundant between cohorts. In particular, 7 genera (Bacteroides, Blautia, Faecalibacterium, Roseburia, Pseudobutyrivibrio, Anaerostipes, and Subdoligranulum) were all significantly enriched in the healthy oral samples compared to the DCIS and breast cancer oral samples. To determine whether the taxonomic differences we observed between the cohorts’ gut and oral microbiota corresponded to functional differences, we performed a predictive functional analysis using Piphillin which identified 35 KEGG pathways differentially present in the gut microbiota and 8 pathways differentially present in the oral samples. Understanding how gut and oral microbiomes relate to breast cancer may open up new opportunities for the development of novel markers for early detection (or markers of susceptibility) as well as new strategies for prevention and/or treatment. Citation Format: Michael J. Campbell, Emma McCune, Breanna Johnson, Tess O'Meara, Diane Heditsian, Susie Brain, Laura Esserman. Breast cancer and the human oral and gut microbiomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2830.

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