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

Sheetal Parida, Dipali Sharma, Sheetal Parida, Dipali Sharma

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 contributes to many organ specific cancers [1,15,16].

Conflict of interest statement

Disclosure statement

All authors declare that they have no conflict of interest.

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Fig. 1.
Fig. 1.
A schematic representation of the planned analyses. Patient data from previous studies were analyzed to define common trends among their results as well as unique aspects using One Codex (a bioinformatics platform for microbial genomics).
Fig. 2.
Fig. 2.
(A) Relative abundance of major phyla. (B) Percentage of three major phyla, Firmicutes, Bacteroides and Proteobacteria. (C) Relative percentage of lactobacillus species in breast cancer compared to control. (D) Frequency of occurrence of abundant taxa in control and cancer tissue samples (SRP076038, Analysis: One Codex).
Fig. 3.
Fig. 3.
(A) Phylum distribution of local breast microbiota in cancer and nearby normal tissue samples. (B) Mean percentages of major phyla in cancer and nearby normal breast tissue samples. (C) Percentage of three major phyla, Firmicutes, Bacteroides and Proteobacteria. (D) Frequency of occurrence of abundant taxa in breast cancer and nearby normal tissue samples (PRJEB4755, Analysis: One Codex).
Fig. 4.
Fig. 4.
(A) Phylum distribution of breast ductal microbiota in Nipple aspirate fluid of breast cancer survivors and healthy volunteers. (B) Mean percentages of major phyla in nipple aspirate fluid of breast cancer survivors and healthy volunteers. (C) Percentage of three major phyla, Firmicutes, Bacteroides and Proteobacteria. (D) Frequency of occurrence of abundant taxa in NAF of breast cancer survivors and healthy volunteers (SRP071608, Analysis: One Codex).
Fig. 5.
Fig. 5.
(A) Phylum distribution in local breast microbiota of breast cancer patients having benign and malignant disease. (B) Mean percentages of major phyla in benign and malignant breast cancer tissue samples. (C) Percentage of three major phyla, Firmicutes, Bacteroides and Proteobacteria. (D) Frequency of occurrence of abundant taxa in benign and malignant breast tissue samples (PRJNA335375, EBI-ENA, Analysis: OneCodex).

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Source: PubMed

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