Few studies have formally tested the interaction between diet and the gut microbiome in the context of cardiometabolic health, particularly with the microbiome considered as a potential mediator rather than a target of dietary effects. Here, we investigated 307 male participants in the Health Professionals Follow-Up Study who provided up to four stool samples each, yielding 925 shotgun metagenomes and 340 metatranscriptomes, long-term dietary information, and biomarkers of glucose homeostasis, lipid metabolism, and inflammation from blood samples. We demonstrate that a healthy Mediterranean-style dietary pattern is associated with functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary, depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings represent a step forward in the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.
