Prebiotics promote health and have a positive effect on the gut microbiome. Omega-3 fatty acids have been linked to changed gut microbiome composition and are widely thought to be beneficial to human health, although recent large trials have been conflicting. In a 6-week diet intervention, the researchers compared the effects of daily omega-3 supplementation (500 mg) to 20g of a well-characterized prebiotic, inulin. Bifidobacterium and Lachnospiraceae levels increased significantly after inulin supplementation. While, increased Coprococcus spp. and Bacteroides spp., as well as decreased Collinsella spp. was observed after omega-3 supplementation. However, considerable increases in butyrate, iso-valerate, and iso-butyrate (p<.004) resulted in inulin supplementation and considerable increases in iso-butyrate and isovalerate (p<.002), and some increases in butyrate (p<.053) was resulted with omega-3 supplementation. After adjusting for confounders, it was found that Coprococcus was positively linked with iso-butyric acid (Beta (SE)=0.69 (0.02), P=1.4 x 10−3) and negatively linked with triglyceride-rich lipoproteins such as VLDL (Beta (SE)=−0.381 (0.01), P = .001) and VLDL-TG (Beta (SE)=−0.372 (0.04), P=.001). The gut microbiome composition and some of its cardiovascular benefits appear to be modulated by dietary omega-3, possibly via a prebiotic effect.