Diet shapes the gut microbiome: cross-sectional and longitudinal insights from the Human Phenotype Project

Diet is a major environmental factor influencing the human gut microbiome. However, the effects of specific foods and dietary patterns on microbial composition, diversity, and function is not fully understood, limiting progress toward personalized dietary strategies. Leveraging 10,064 participants from the Human Phenotype Project with app-based diet logs and shotgun metagenomics, we predicted diet-microbiome associations at species-level resolution. Diet significantly predicted microbial diversity (Richness r=0.24, Shannon index r=0.22), the relative abundance of 664 of 724 species tested (91.5%, FDR<0.05), and 313 of 320 functional pathways (97.8%, FDR<0.05). Feature attribution identified distinct food-microbe links, including coffee with Lawsonibacter asaccharolyticus (r=0.41), yogurt with Streptococcus thermophilus (r=0.38), and milk with Bifidobacterium species (r=0.31-0.35). In parallel, broader dietary patterns, especially those related to the degree of food processing, emerged as predictors of microbial diversity and composition. Longitudinal analyses on test set data showed that models remained predictive over two and four years (R²=0.73-0.79), with significant associations between observed and predicted changes in 115 and 92 species, respectively. Finally, we developed an exploratory analysis for suggesting personalized dietary interventions with predicted microbiome shift effects that are associated with improvements in key clinical biomarkers such as triglycerides. Overall, our findings establish diet as a key modulator of microbiome composition, diversity, and function, and highlight its potential for guiding personalized interventions.