Macronutrients, Microbiota, and Metabolism: Dietary Strategies Against Obesity and Diabetes

Abstract

Obesity and type 2 diabetes (T2D) are escalating global health crises, driven by metabolic dysfunctions such as insulin resistance (IR), chronic inflammation, and dyslipidemia. Conventional dietary recommendations have shown limited success in halting these conditions, emphasizing the urgent need for targeted, mechanistically informed strategies. Recent research underscores the pivotal role of gut microbiota in mediating host metabolism, providing a new frontier for nutritional interventions. This review synthesizes current evidence on how dietary macronutrients influence gut microbiota composition and function, ultimately affecting metabolic outcomes. It highlights the central role of microbial metabolites, particularly short-chain fatty acids (SCFAs), in modulating glucose homeostasis, adiposity, and inflammation. The review discusses how diets rich in fiber and polyphenols enhance microbial diversity and SCFAs production, improving insulin sensitivity and weight regulation. Conversely, excessive intake of saturated fats and refined sugars is shown to disrupt gut microbial balance, promoting dysbiosis and metabolic derangements. Evidence from clinical and preclinical studies on dietary strategies, including Mediterranean, low-carbohydrate, and intermittent fasting (IF) approaches is critically evaluated for their microbiota-mediated effects. Finally, the review advocates personalized nutrition, integrating gut microbial profiles to optimize dietary interventions in obesity and diabetes management. Future research should prioritize the identification of precise microbial signatures and metabolites that predict individual responses to dietary interventions. Advances will enable the development of personalized, microbiota-targeted nutritional therapies. Integrating dietary modulation with gut microbiome profiling holds the promise of transforming obesity and diabetes care into a more precise and effective discipline