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posted on 2023-03-31, 04:25 authored by David R. Soto-Pantoja, Mohamed Gaber, Alana A. Arnone, Steven M. Bronson, Nildris Cruz-Diaz, Adam S. Wilson, Kenysha Y.J. Clear, Manuel U. Ramirez, Gregory L. Kucera, Edward A. Levine, Sophie A. Lelièvre, Lesley Chaboub, Akiko Chiba, Hariom Yadav, Pierre-Alexandre Vidi, Katherine L. Cook Effect of PUFA on apical polarity in S1 acini. S1 cells cultured in 3D were treated following differentiation (days 8-12) with 10 μM of n-6 arachidonic acid (AA) or with vehicle (ethanol). (A) Representative confocal images of acini treated with vehicle or arachidonic acid (AA) and stained for ZO-1. DAPI was used to counterstained nuclei. Arrows point at nonpolarized ZO-1 and the dashed circle outlines the location of apical ZO-1. (B) Bar graph of the percentages of acini with apically polarized ZO-1 following treatments with vehicle or AA. **p < 0.01. Size bar, 5 μm
Funding
Chronic Disease Research Fund
American Cancer Society Research Scholar
Komen Foundation
American Institute for Cancer Research
NIH NCI
Department of Defense Breast Cancer Research Program
National Cancer Center's Comprehensive Cancer
History
ARTICLE ABSTRACT
Obesity and poor diet often go hand-in-hand, altering metabolic signaling and thereby impacting breast cancer risk and outcomes. We have recently demonstrated that dietary patterns modulate mammary microbiota populations. An important and largely open question is whether the microbiome of the gut and mammary gland mediates the dietary effects on breast cancer. To address this, we performed fecal transplants between mice on control or high-fat diets (HFD) and recorded mammary tumor outcomes in a chemical carcinogenesis model. HFD induced protumorigenic effects, which could be mimicked in animals fed a control diet by transplanting HFD-derived microbiota. Fecal transplants altered both the gut and mammary tumor microbiota populations, suggesting a link between the gut and breast microbiomes. HFD increased serum levels of bacterial lipopolysaccharide (LPS), and control diet–derived fecal transplant reduced LPS bioavailability in HFD-fed animals. In vitro models of the normal breast epithelium showed that LPS disrupts tight junctions (TJ) and compromises epithelial permeability. In mice, HFD or fecal transplant from animals on HFD reduced expression of TJ-associated genes in the gut and mammary gland. Furthermore, infecting breast cancer cells with an HFD-derived microbiome increased proliferation, implicating tumor-associated bacteria in cancer signaling. In a double-blind placebo-controlled clinical trial of patients with breast cancer administered fish oil supplements before primary tumor resection, dietary intervention modulated the microbiota in tumors and normal breast tissue. This study demonstrates a link between the gut and breast that mediates the effect of diet on cancer.
This study demonstrates that diet shifts the microbiome in the gut and the breast tumor microenvironment to affect tumorigenesis, and oral dietary interventions can modulate the tumor microbiota in patients with breast cancer.
