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Microbiomes of Breast Cancer, Normal Tissue Differ

NEW YORK (GenomeWeb) – The microbiomes of breast tissue isolated from women with cancer and those from women with benign disease differ, according to a new study from a Mayo Clinic team of researchers.

Using 16S rDNA sequencing, the team examined the microbial signatures of breast tissues collected during surgery from women with breast cancer and compared it to those from skin and buccal swabs obtained at the same time. As the Mayo's Tina Hieken and her colleagues reported in Scientific Reports today, they found that the breast tissue microbiota was distinct. Further, when the researchers compared it to the microbiome of breast tissue from women with benign disease, they noticed that women with malignant disease harbored markedly different microbial communities.

"Our research found that breast tissue samples obtained in the operating room under sterile conditions contain bacterial DNA, even when there is no sign of infection," Hieken said in a statement. "Furthermore, we identified significant differences in the breast tissue microbiome of women with cancer versus women without cancer."

Hieken and her colleagues sterilely collected breast tissue from 33 patients — none of whom had evidence of an infection at the time and none of whom developed a post-operative infection — as well as overlying breast skin tissue, skin swab, and buccal swab samples. Through 16S rDNA sequencing, the researchers detected 1,460 operational taxonomic units, or about 454 OTUs per sample.

Principal coordinates analysis separated each sample type into its own cluster. Although the breast and skin tissue samples were more similar to each other than to the skin and buccal swabs, the samples were distinct, the researchers reported.

In particular, the researchers' analyses indicated that breast tissue microbiome differs from breast skin tissue microbiome in rare bacterial lineages. Hieken and her colleagues noted that breast tissue is richer in bacterial species than breast skin tissue, though their species evenness is about the same. Their β-diversity analysis showed a highly significant difference in community membership between the two microbiota, though that difference disappeared in a weighted analysis. This suggested to the researchers that the microbiomes differed in rare lineages.

They noted that differentially abundant taxa between the two included ones belonging to Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria.

Hieken and her colleagues also collected adjacent normal breast tissue samples from 13 women with benign breast disease and from 15 women with invasive cancer for microbial analysis. The normal breast tissue adjacent to invasive cancer was significantly different from normal breast tissue adjacent to benign disease, they reported.

While α- and Shannon diversity indices were similar between the two, β-diversity analysis indicated that the microbial community in normal tissue near invasive disease differs from that of normal tissue near benign disease. In particular, the researchers reported an increased relative abundance of Fusobacterium, Atopobium, Hydrogenophaga, Gluconacetobacter, and Lactobacillus.

In addition, a KEGG pathway analysis uncovered six pathways that are differentially abundant between the two groups. Patients with malignant disease had reduced inositol phosphate metabolism, while patients with benign disease had increased cysteine and methionine metabolism, glycosyltransferases, and fatty acid biosynthesis.

This, the researchers said, suggests that dybiosis of this microbial community could contribute to cancer development.

"There is mounting evidence that changes in the breast microbiome may be implicated in cancer development and the aggressiveness of cancer and that eliminating dangerous microorganisms or restoring normal microbiota may reverse this process," Mayo's Nick Chia added in a statement.

He and his colleagues cautioned, however, that their study relied on a small sample size and that all the patients had estrogen receptor-positive tumors. A larger and more diverse cohort needs to be studied to uncover any microbial signature of malignant disease, they added.