Omega-3 Polyunsaturated Fatty Acids, Gut Microbiota, Microbial Metabolites, and Risk of Colorectal Adenomas

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are thought to protect against colorectal adenoma (CRA) development. We aimed to further understand the underlying mechanisms by examining the relationships between omega-3 PUFAs and the gut microbiota on CRAs. We assessed the mucosal microbiota via bacterial 16S rRNA sequencing among 217 CRA cases and 218 controls who completed PUFA intake questionnaires. The overall microbial composition was assessed by alpha-diversity measurements (diversity, richness, and evenness). Global metabolomics was conducted using a random subset of case-control pairs (n = 50). We compared microbiota and metabolite signatures between cases and controls according to fold change (FC). Odds ratios (OR) and confidence intervals (CI) were estimated from logistic regression for associations of omega-3 PUFAs and the microbiota with CRAs. We observed an inverse association between overall omega-3 PUFA intake and CRAs, especially for short-chain omega -3 PUFAs (OR = 0.45, 95% CI: 0.21, 0.97). Such inverse associations were modified by bacterial evenness (p(-interaction) = 0.03). Participants with higher levels (FC > 2) of bile acid-relevant metabolites were more likely to have CRAs than the controls, and the correlation between bile acids and bacterial diversity differed by case-control status. Our findings suggest that omega-3 PUFAs are inversely associated with CRA development, and the association may be modified by gut microbiota profiles.