The power of small changes: Comprehensive analyses of microbial dysbiosis in breast cancer

Abstract

Disparate occurrence of breast cancer remains an intriguing question since only a subset of women with known risk factors develop cancer. Recent studies suggest an active role of local and distant microbiota in breast cancer initiation, progression, and overall prognosis. A dysbiotic microbiota predisposes the body to develop cancer by inducing genetic instability, initiating DNA damage and proliferation of the damaged progeny, eliciting favorable immune response, metabolic dysregulation and altered response to therapy. In this review, we present our analyses of the existing datasets and discuss the local dysbiosis observed in breast cancer patients and different aspects of breast carcinogenesis that can be potentially influenced by local breast microbiota. Striking differences between microbial community compositions in breast of cancer patients compared to healthy individuals were noted. Differences in microbiome were also apparent between benign and malignant disease and between nipple aspirate fluid of healthy individuals and breast survivors. We also discuss the identification of distinct bacterial, fungal, viral as well as parasite signatures for breast cancer. These microbes are capable of producing numerous secondary metabolites that can act as signaling mediators effecting breast cancer progression. We review how microbes potentially alter response to therapy affecting drug metabolism, pharmacokinetics, anti-tumor effects and toxicity. In conclusion, breast harbors a community of microbes that can communicate with the host cells inducing downstream signaling pathways and modulating various aspects of breast cancer growth and metastatic progression and an improved understanding of microbial dysbiosis can potentially reduce breast cancer risk and improve outcomes of breast cancer patients. The human microbiome, now referred to as, the “forgotten organ” contains a metagenome that is 100-fold more diverse compared to the human genome, thereby, is critically associated with human health [ 1 , 2 ]. With the revelations of the human microbiome project and advent of deep sequencing techniques, a plethora of information has been acquired in recent years. Body sites like stomach, bladder and lungs, once thought to be sterile, are now known to harbor millions of indigenous microbial species. Approximately 80% of the healthy microbiome consists of Firmicutes and Bacteroidetes accompanied by Verrucomicrobia , Actinobacteria , Proteobacteria , Tenericutes and Cyanobacteria [ 2 – 7 ]. The role of microbiome in diabetes, obesity and even neurodegenerative diseases was greatly appreciated in the last decade [ 1 , 7 – 14 ] and now it has been established that microbiome significantly contr...

Predictive Metagenomic Profiling, Urine Metabolomics, and Human Marker Gene Expression as an Integrated Approach to Study Alopecia Areata

“…A decrease in some species such as Candidatus Aquiluna rubra and Staphylococcus epidermidis and an increase in the Neisseria genus at the dermis level revealed specific characteristics associated with AA. Interestingly, Candidatus Aquiluna rubra, a marine member of the Actinobacteria class, was previously found to be considerably less abundant in breast cancer patients than in healthy controls (Parida and Sharma, 2019). We also found an increase in gram-positive anaerobic cocci such as Anaerococcus.…”

The virome of HPV-positive tonsil squamous cell carcinoma and neck metastasis

“…NPR ("negativenode primary"), PPR ("positive-node primary"), NLN ("negative lymph node"), PLN ("positive lymph node"), CTRL ("control"), HPV (human papilloma virus), PNI (perineural invasion), LVI (lymphovascular invasion), T stage (tumor stage). literature suggest that host microbiome interactions effect oncologic outcomes [16,17,40,41]. Specifically, it has been shown that the breast microbiome interacts with host cells to impact signaling pathways, ultimately modulating breast cancer growth and metastatic progression [40].…”

“…literature suggest that host microbiome interactions effect oncologic outcomes [16,17,40,41]. Specifically, it has been shown that the breast microbiome interacts with host cells to impact signaling pathways, ultimately modulating breast cancer growth and metastatic progression [40]. Within the pancreatic cancer literature, research has demonstrated that differences in microbiome diversity and the presence of specific microbial signatures predict longterm pancreatic adenocarcinoma survival [41].…”

Microbiome and Breast Cancer: New Role for an Ancient Population

“…Local dysbiosis is observed in BC tissue compared to non-BC tissue. The analysis of published data sets with bioinformatics platform for microbial genomics revealed that the composition of microbiome community varies in patients with BC in different ethnicities; it also varies in nipple aspirate of survivors compared to those of the healthy individuals, is different in benign and malignant BC tissue, and varies in BC subtypes (17). To explain it, Urbaniak et al identified eight new species and seven bacterial phyla in breast tissue samples.…”

“…Moreover, the effects and mechanisms of microbiome on different therapeutic approaches such as hormone, chemo-, radio-, and immuno-therapy of BC were scrutinized. Although there are some reviews on microbiome and breast cancer (14)(15)(16)(17)(18), little is known about the clinical applications of the microbiome such as probiotics, microbiome genome modulation, and engineered microbiome enzymes in BC therapy, which also were discussed at the end.…”