The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

Abstract

Regardless of the global progress in early diagnosis and novel therapeutic regimens, breast carcinoma poses a devastating threat, and the advances are somewhat marred by high mortality rates. Breast cancer risk prediction models based on the known risk factors are extremely useful, but a large number of breast cancers develop in women with no/low known risk. The gut microbiome exerts a profound impact on the host health and physiology and has emerged as a pivotal frontier in breast cancer pathogenesis. Progress in metagenomic analysis has enabled the identification of specific changes in the host microbial signature. In this review, we discuss the microbial and metabolomic changes associated with breast cancer initiation and metastatic progression. We summarize the bidirectional impact of various breast cancer-related therapies on gut microbiota and vice-versa. Finally, we discuss the strategies to modulate the gut microbiota toward a more favorable state that confers anticancer effects.

Keywords: Microbiome; anticancer; breast cancer; dysbiosis; gut microbiota; therapy.

Figure 1.

An overview on the plethora of factors that regulate the gut microbiota and, subsequently, its downstream physiological functions. The gut microbes are critical for maintaining host health as they regulate a multitude of systemic functions as well as the immune system and, thus, confer a protective role against pathogens and carcinogens. The red arrows depict the regulatory impact of the different factors on the host microbiota. The green arrows denote the effect of the gut microbiota on the various functions within the host that help to maintain health of the subject.

Figure 2.

There is a significant shift in the gut microbial composition in breast cancer subjects compared to healthy women, which is accompanied by alterations in the relative abundance of distinct microbial species and families.

Figure 3.

Reversal of microbial dysbiosis can aid in inhibition of breast tumor development and progression by mounting the immune system and rewiring the cancer-associated pathways. Consumption of probiotics and a diet rich in fibers and polyphenols is likely to enrich the beneficial gut microbiota, which can impart an anti-tumor effect in breast cancer models. The red arrow indicates the various stages in the development of breast tumor, followed by subsequent metastasis. The green arrow depicts the suppression of breast tumorigenesis, following reversal of gut dysbiosis. The application of the gut microbiota in combination with contemporary therapeutic modules is a research focus for further investigations.