Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study

Abstract

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case‐control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population‐based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray‐Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13‐0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen‐conjugating and immune‐related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially‐mediated mechanisms of breast disease.

The involvement of oncobiosis and bacterial metabolite signaling in metastasis formation in breast cancer

“…Multiple microbial compartments undergo oncobiotic transformation during breast cancer, including breast tissue [55,56], milk ducts [57], the inherent microbiome of the breast carcinoma [54,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72], the distal gut [51,52,[73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88][89], and the urinary microbiome [54,90]. However, no differences in the microbiome of the nipple [57,69] and the oral microbiome [54] between healthy individuals and breast cancer patients have been detected.…”

“…The gut microbiome undergoes oncobiotic transformation in breast cancer [21,51,52,[73][74][75][76][77][78][79][80][81][82]. In terms of diversity indices, Goedert and colleagues [73] and Byrd and colleagues [74] reported lower or trends towards lower diversity indices in three different cohorts, while Zhu and colleagues [75] and Bobin-Dubigeon and co-workers [84] reported increased alpha diversity indices. Howe and co-workers [76] reported increases in alpha diversity indices in a Pten-deficient mouse model backing the observations of Zhu and colleagues [75] and Bobin-Dubigeon and co-workers [84].…”

“…Goedert and colleagues provided strong evidence for the involvement of Clostridiales in estrogen reactivation in breast cancer patients [73,121,122]. The oncobiome has increased capacity to reactivate estrogens [21,50,73,74,83,[121][122][123][124] enabling their reuptake and supporting the growth of estrogen-dependent, estrogen receptor-positive (ER +) breast tumors. Of note, the capacity for estrogen reactivation was identified by pathway analysis in the breast and nipple aspirate microbiomes [57].…”

“…On the other hand, the gut microbiome plays a pivotal role in fine-tuning the host's immune system. In a large-cohort fecal microbiome study, multiple taxa immune-related functions were strongly associated with breast cancer [74]. In murine models, Lactobacillus acidophilus [39] or Helicobacter hepaticus [266] were associated with immune function in breast cancer.…”

Exercise and Prebiotic Fiber Provide Gut Microbiota-Driven Benefit in a Survivor to Germ-Free Mouse Translational Model of Breast Cancer

“…Despite medical advances in detection, diagnostics, and treatment, which have improved survival, individuals with breast cancer comprise a large population which would benefit from improved treatment and health outcomes. Breast cancer is associated with an altered gut microbial profile compared to that of healthy controls [ 27 , 28 , 29 ], and treatments such as chemotherapy can further alter the gut microbiota toward dysbiosis [ 30 , 31 , 32 , 33 ]. Multiple studies have implicated the gut microbiota, and in some cases specific microbes, in successful response to various chemotherapies [ 8 , 9 , 34 , 35 ], suggesting similar mechanisms may support successful response to common breast cancer chemotherapeutics.…”