Food Pairing Pattern Independently Associated with Cardiometabolic Traits Beyond Dietary Indices Across Eastern and Western Populations

Cardiometabolic health is closely linked to diet. Both specific food choices and dietary indices are commonly used to guide cardiometabolic protection strategies. However, the balance between foods may also significantly impact cardiometabolic health. Here, we explore the balance and imbalance in long-term dietary food intake to quantify food pairing patterns, providing insights beyond conventional dietary indices and single-food intake frequencies. Using data from our Guangdong Gut Microbiome Project (GGMP; n = 6994) and the National Health and Nutrition Examination Survey (NHANES; n = 7350) cohorts, we observed that long-term food pairing patterns are independent of single food intake frequency and dietary indices. We identified 1759 and 306 cardiometabolic-related long-term food pairing patterns from two cohorts (false discovery rate (FDR) < 0.05), respectively. Notably, around 80% of these pairing foods not individually associated with cardiometabolic traits, and food pairing pattern associations with cardiometabolic traits at hyper food group level were consistent across Eastern and Western populations. Besides, mediation analysis revealed that 72.7% of long-term food pairing patterns affected cardiometabolic traits through 31 microbial genera, with Clostridiumsensustricto1 playing a predominant role. Moreover, multi-step mediation analysis found that microbes mediated the impact of long-term food pairing patterns on cardiometabolic traits primarily through their metabolic pathways, such as pyruvate fermentation to propanoate and ergothioneine biosynthesis pathways. Our data suggest that balance between dietary foods is broadly associated with cardiometabolic traits by modulating gut microbial functionalities, in contrast to the lower occurrence when considering individual foods in isolation. These results offer a novel perspective for designing personalized dietary strategies beyond present dietary indices to enhance cardiometabolic health.