Diet modulates the gut microbiome, metabolism, and mammary gland inflammation to influence breast cancer risk

Several studies have indicated a strong link between obesity and the risk of breast cancer.
Obesity decreases gut microbial biodiversity and modulates Bacteroidetes-to-Firmicutes
proportional abundance, suggesting that increased energy-harvesting capacity from indigestible
dietary fibers and elevated lipopolysaccharide bioavailability may promote inflammation. To
address the limited evidence linking diet-mediated changes in the gut microbiota to breast
cancer risk, we aimed to determine how diet affects the microbiome and breast cancer risk.
Female 3-week-old BALB/c mice were fed six different diets (control, high-sugar, lard, coconut
oil, lard+flaxseed oil, and lard+safflower oil) for 10 weeks. Fecal 16s sequencing was performed
for each group. Diet shifted fecal microbiome populations and modulated mammary gland
macrophage infiltration. Fecal conditioned media shifted macrophage polarity and inflammation.
In our DMBA-induced breast cancer model, diet differentially modulated tumor and mammary
gland metabolism. We demonstrated how dietary patterns change metabolic outcomes, and gut
microbiota, which may contribute to breast tumor risk. Furthermore, we showed the influence of
diet on metabolism, inflammation, and macrophage polarity. This study suggests that dietary-
microbiome interactions are key mediators of breast cancer risk.