Distinct microbial communities that differ by race, stage, or breast-tumor subtype in breast tissues of non-Hispanic Black and non-Hispanic White women

Abstract

Growing evidence highlights an association between an imbalance in the composition and abundance of bacteria in the breast tissue (referred as microbial dysbiosis) and breast cancer in women. However, studies on the breast tissue microbiome have not been conducted in non-Hispanic Black (NHB) women. We investigated normal and breast cancer tissue microbiota from NHB and non-Hispanic White (NHW) women to identify distinct microbial signatures by race, stage, or tumor subtype. Using 16S rRNA gene sequencing, we observed that phylum Proteobacteria was most abundant in normal (n = 8), normal adjacent to tumor (normal pairs, n = 11), and breast tumors from NHB and NHW women (n = 64), with fewer Firmicutes, Bacteroidetes, and Actinobacteria. Breast tissues from NHB women had a higher abundance of genus Ralstonia compared to NHW tumors, which could explain a portion of the breast cancer racial disparities. Analysis of tumor subtype revealed enrichment of family Streptococcaceae in TNBC. A higher abundance of genus Bosea (phylum Proteobacteria) increased with stage. This is the first study to identify racial differences in the breast tissue microbiota between NHB and NHW women. Further studies on the breast cancer microbiome are necessary to help us understand risk, underlying mechanisms, and identify potential microbial targets.

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

“…172 We identified a unique TNBC microbial signature, with high Streptococcaceae and Ruminococcus abundance in breast tumors and tumor-adjacent breast tissue, compared to normal mammary tissue from healthy subjects. 9 We reported that microbes vary by tumor stage and subtype. Critically, we showed for the first time that abundance of microbes and microbial ratios vary by race, with African Americans displaying greater microbial dysbiosis compared to tumors from European American patients.…”

“…Critically, we showed for the first time that abundance of microbes and microbial ratios vary by race, with African Americans displaying greater microbial dysbiosis compared to tumors from European American patients. 9 Interestingly, race is one of the strongest associations for microbes, pathways, and clinical metadata according to the Human Microbiome Project Consortium study from 2012 but notably, breast was not studied. 1 The largest study to examine microbes and BC was from The Cancer Genome Atlas (TCGA) wherein Proteobacteria, Actinobacteria, and Firmicutes were shown as the most abundant phyla in breast tumors, which is consistent with our work and others, and reminiscent of the gut.…”

“…We have published that certain microbes correlate with tumor stage, tumor subtype, and race in BC patients. 9 Microbes also regulate immunological response to therapy and anti-tumor immunity with bona fide impacts on clinical outcomes. For example, Akkermansia muciniphila, which confers metabolic benefits despite colonizing the gut in low abundances, restored sensitivity to immune checkpoint blockade (ICB) therapy in murine models and correlated with ICB therapeutic response in BC patients.…”

Immunometabolism: From basic mechanisms to translation

“…Interestingly, microbial dysbiosis and specific microbes including bacteria and fungi correlate with several cancers, notably tumor subtypes, stage, or race in breast cancer. 91 Furthermore, certain microbes have been shown to impact response to immune checkpoint blockade in anti-tumor therapy in mice and correlate with therapeutic response in humans. [92][93][94] Based on these and other related studies, it is possible that immune perturbations resulting from microbiome composition and microbially modified metabolites can be targeted for therapeutic benefit.…”

Indoxylsulfate, a Metabolite of the Microbiome, Has Cytostatic Effects in Breast Cancer via Activation of AHR and PXR Receptors and Induction of Oxidative Stress

“…Several studies demonstrated oncobiosis in the distal gut [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ], the breast microbiome [ 19 , 20 , 21 , 22 , 23 , 24 ], and oral and urinary microbiomes [ 22 ] in breast cancer patients. A majority of the reports show decreased diversity in breast cancer patients compared to controls [ 1 , 2 , 3 , 4 , 5 , 8 , 9 , 12 , 13 , 14 , 15 , 18 ]. Antibiotic use can suppress diversity, and in murine experimental models of breast cancer, the combination of Vancomycin, Neomycin, Metronidazole, Amphotericin, and Ampicillin aggravated the disease [ 25 , 26 ].…”