Weight loss and omega-3 supplementation modulate the microbiome in women with increased breast cancer risk.

Obesity is associated with gut dysbiosis, chronic inflammation, and insulin resistance. We assessed proportional change in fecal microbial populations in a pilot study (n=34) of peri/postmenopausal women with BMI ≥28 kg/m2 who were randomized to receive either 3.25 g/day of omega-3 fatty acids or a placebo during a weight loss intervention. Body composition was assessed using DXA, and fecal and blood samples were collected. Median weight change was -10%. Among participants who lost ≥10% of their weight, those assigned to omega-3 fatty acids showed the greatest decrease in the Firmicutes/Bacteroidetes phyla ratio and displayed favorable changes in systemic biomarkers. Notable increases in the proportional abundance of short-chain fatty acid (SCFA)-producing microbes including Phocaeicola vulgatus and Alistipes putredinis were observed in women receiving omega-3, which correlated with improvements in breast cancer biomarkers such as bioavailable estradiol, adiponectin-to-leptin ratio, and C-reactive protein levels. Women administered omega-3 fatty acids displayed increased % change in plasma SCFA propionate and decreased butyrate, suggesting intervention differentially modulated circulating bacterial-derived SCFA metabolites. High dose omega-3 fatty acids, when added to a behavioral weight loss intervention, promoted beneficial shifts to the gut microbiome and associated with improved breast cancer risk factors biomarkers.