574 Background: Sulfidogenic bacteria produce hydrogen sulfide, the excess of which is genotoxic and proinflammatory and is absorbed through the GI tract into the systemic circulation. The role of sulfidogenic bacteria in BC has not been explored. In this study, we aimed to evaluate sulfidogenic bacterial abundance and diversity in BC. We hypothesized that there will be lower alpha and beta diversity in BC groups. We also hypothesized that there will be a higher relative abundance of sulfidogenic bacteria in BC vs. controls. Methods: We used high throughput sequencing of the dsrA gene in stool samples of female participants with BC and controls without BC (n=283). Controls were further delineated into normal mammogram, abnormal mammogram with no evidence of BC (e.g. cysts, etc), and controls without BC but with a first degree relative who has BC. To process the sequences, QIIME2 bioinformatics pipelines were used with taxonomy assigned using the SILVA database. We performed alpha diversity analyses with nonparametric statistics, and beta diversity analyses using the Bray-Curtis and weighted/unweighted UniFrac metrics. Differential abundance of sulfidogenic bacteria at the genus level was calculated in R using the DESeq2 package. In the same samples, we used sequencing of the V3-V4 region of the 16s rDNA gene to compare relative abundance of total sulfidogenic bacteria between BC samples and controls in R using the DESeq2 package. Results: Using the Chao1 metric, we found higher sulfidogenic alpha diversity in BC vs. all controls (p < 0.001), BC vs. controls who have a first degree relative with BC (p = 0.005). as well as within controls with a normal mammogram vs. abnormal mammogram without BC (p = 0.037). We did not find significant differences in beta diversity between BC vs. controls. When analyzed visually using PCoA of unweighted UniFrac distances, there were two clusters within all patient groups, indicative of two enterotypes across all subjects. We did not find a significant difference in the relative abundance of overall sulfidogenic bacteria as identified by the 16S rDNA gene between BC and controls. However, Desulfovibrio was enriched in BC compared to normal mammogram samples with a log fold change of 1.69 (p = 0.013). Conclusions: These results suggest altered sulfidogenic gut bacterial community composition in individuals with BC, particularly in organisms with lower relative abundance. Desulfovibrio appears as a predominating organism in BC. This is supported by prior research, which suggests Desulfovibrio becomes less abundant in participants exposed to agents that inhibit BC cell proliferation. We propose that there are two enterotypes of sulfidogenic gut bacteria in women.
Khan et al. (Wed,) studied this question.