The study was presented by Katherine Cook, PhD, during a poster session at the San Antonio Breast Cancer Symposium. Dr. Cook is a researcher at Wake Forest University, Winston-Salem, N.C.
Obesity increases risk of breast cancer, but it also alters the composition of the gut microbiome. Obesity is associated with a greater frequency of Firmicute bacteria phyla, compared with Bacteroidetes phyla, while abnormally low ratios are associated with inflammatory bowel disease.
In mice, the researchers previously showed that diet can lead to changes in the microbiome of both the gut and the breast. They conducted fecal transplants between mice who were fed normal or high-fat diets (HFD), and then used a chemical carcinogenesis model to investigate the impact on tumor outcomes. They observed changes in the microbiota populations in both the gut and the mammary glands when mice fed a normal diet received fecal transplants from HFD mice. On the other hand, when HFD mice received fecal transplants from mice with normal diets, the transplants countered the increase in serum lipopolysaccharide levels associated with HFD. In vitro models showed that microbiota from HFD mice also altered the epithelial permeability of breast tissue, and infection of breast cancer cells with HFD microbiota led to greater proliferation.
The researchers also examined breast cancer tissue from women who received omega-3 PUFA supplements or placebo before undergoing primary tumor resection, and found that there were differences in the proportional abundance of specific microbes between tumor and adjacent normal tissue, with the former having excess of Lachnospiraceae and Ruminococcus. The finding suggests that these bacteria may grow better in a tumor microenvironment, and could play a role in breast cancer cell signaling. The supplements altered the microbiota of both normal and breast cancer tissue.
In the study presented at SABCS, the researchers analyzed fecal samples from 34 obese and overweight postmenopausal women involved in a weight-loss trial, who received 3.25 g/day of omega-3 PUFA supplements or placebo combined with calorie restriction and exercise. They performed metagenomic sequencing from the fecal samples at baseline and 6 months to determine microbiome populations.
Women who experienced weight loss, with or without omega-3 PUFA supplementation, had a decline in the abundance of Firmicutes phyla – a group linked to inflammation risk – as a percentage of overall bacterial phyla. The researchers found a similar trend among women who received omega-3 PUFA, regardless of how much weight they lost. At the species level, those who received supplements had higher proportional abundance of Phocaeicola massiliensis and reduced proportions of Faecalibacterium prausnitzii, R. lactaris, Blautia obeum, and Dorea formicigenerans (P < .05).
Weight loss combined with supplementation also seemed to affect gut microbiota, with subjects who lost more than 10% of their body weight and received omega-3 PUFA supplements having elevated Bacteriodetes and reduced Firmicutes, compared with all other groups (P < .05).
At 6 months, the researchers grouped women by mean body fat composition, and found both positive and negative correlations among different bacterial species. Finally, the researchers looked at serum levels of the inflammatory cytokines interleukin-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor–alpha at 6 months. Women with elevated levels of at least two cytokines had higher levels of two species of mucin-degrading bacteria. Levels of MCP-1 alone also correlated with greater proportions of mucin-degrading bacteria (P < .05).
The authors concluded that increasing omega-3 PUFA uptake to about 2% of total daily calorie intake could push the gut microbiome in a direction that improves intestinal permeability parameters and reduces chronic inflammation. These changes could lead to a reduction in the risk for postmenopausal breast cancer.
The study was funded by the Breast Cancer Research Foundation.