Evolving concepts: how diet and the intestinal microbiome act as modulators of breast malignancy

Abstract

The intestinal microbiome plays an important role in human physiology. Next-generation sequencing technologies, knockout and gnotobiotic mouse models, fecal transplant data and epidemiologic studies have accelerated our understanding of microbiome abnormalities seen in immune diseases and malignancies. Dysbiosis is the disturbed microbiome ecology secondary to external pressures such as host diseases, medications, diet and genetic conditions often leading to abnormalities of the host immune system. Specifically dysbiosis has been shown to lower circulating lymphocytes, and increase neutrophil to lymphocyte ratio, a finding which has been associated with a decreased survival in women with breast cancers. Dysbiosis also plays a role in the recycling of estrogens via the entero-hepatic circulation, increasing estrogenic potency in the host, which is another leading cause of breast malignancy. Non-modifiable factors such as age and genetic mutations disrupt the microbiome, but modifiable factors such as diet may also lead to profound disruptions as well. A better understanding of dietary factors and how they disrupt the microbiome may lead to beneficial nutritional interventions for breast cancer patients.

Figure 1

Major phylums in children, adults, and elderly detected by pyrosequencing of 16S ribosomal RNA genes [15, 16].

Figure 2

Schematic representation of Peyer's patch organization (also known as gut-associated lymphoid tissue—GALT) shows that the bulk of the tissue is made up by B cells organized in a large and highly active domed follicle. T cells occupy the areas between the follicles. The antigen enters across a specialized epithelium made up of so-called multifenestrated (M) cells. The germinal center is located in the center of the follicle. Cross-section through the Peyer's patch shows the types of cells and the interactions between the cells of the immune system and the microbiome. M cells: multifenestrated cells; Th-17: T cell helper 17; Treg: T regulatory cells; T cells CD8+: effectors T cells; T helper: naïve CD4+ T cells; B cell; SFB: segmented filamentous bacteria.