Synergistic Interplay of Diet, Gut Microbiota, and Insulin Resistance: Unraveling the Molecular Nexus

Abstract This comprehensive review explores the intricate relationship between gut microbiota, diet, and insulin resistance, emphasizing the novel roles of diet‐induced microbial changes in influencing metabolic health. It highlights how diet significantly influences gut microbiota composition, with different dietary patterns fostering diverse microbial communities. These diet‐induced changes in the microbiome impact human metabolism by affecting inflammation, energy balance, and insulin sensitivity, particularly through microbial metabolites like short‐chain fatty acids (SCFAs). Focusing the key mediators like endotoxemia and systemic inflammation, and introduces personalized microbiome‐based therapeutic strategies, it also investigates the effects of dietary components—fiber, polyphenols, and lipids—on microbiota and insulin sensitivity, along with the roles of protein intake and amino acid metabolism. The study compares the effects of Western and Mediterranean diets on the microbiota‐insulin resistance axis. Therapeutic implications, including probiotics, fecal microbiota transplantation (FMT), and personalized diets, are discussed. Key findings reveal that high‐fat diets, especially those rich in saturated fats, contribute to dysbiosis and increased intestinal permeability, while high‐fiber diets promote beneficial bacteria and SCFAs. The review underscores the future potential of food and microbiota interventions for preventing or managing insulin resistance.