Introduction: We applied multi-omics to study individual responses to dietary interventions and their effects on the gut microbiome in a long-term randomized controlled trial of Mediterranean Diet (MedDiet).
Methods: We profiled host genetics (Global Screening Array), the gut microbiome (shotgun metagenomics), and fecal and plasma metabolomics (LC-MS) at baseline and endpoint in the 18-month DIRECT-PLUS Trial with 294 participants randomized into three groups: healthy dietary guidelines, MedDiet and MedDiet + polyphenols (Fig. 1A).
Results: We observed large variability in individuals' responses to dietary interventions: mean coefficients of variation of post-intervention changes: BMI at 92 (Fig. 1B), hs-CRP at 103, and LDL/HDL at 96. Age, sex, baseline factors, and multi-omics collectively explained the variability in post-intervention changes: BMI (4%) and fasting glucose (11%; Fig 1C). Furthermore, the integration of baseline multi-omics significantly enhanced predicting individual diet responsiveness. (AUC from 0.55 to 0.78; Fig. 1D). Our longitudinal analysis revealed MedDiet-induced alterations in metabolites and the gut microbial taxonomy (Fig. 1E, F)
Conclusion: Our study demonstrates the application of multi-omics in predicting personalized responses to dietary intervention, laying the foundation for precision nutrition in metabolic disease prevention.
D. Dong: None. Y. Liu: None. M. Stampfer: Advisory Panel; Elysium Health. I. Shai: None. C. Huttenhower: Advisory Panel; Seres Therapeutics, Empress Therapeutics, ZOE Nutrition. D. Wang: None.
National Institutes of Health (R01NR01999, R00DK119412, P30DK046200); Deutsche Forschungsgemeinschaft (209933838); The Israel Ministry of Health (87472511); The Israel Ministry of Science and Technology (3-13604)
