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

Ayesha Mubeen Farooq
Medicine, Gandhi Medical College, Secunderabad, India
Tejaswini Kurapati
Medicine, Narayana Medical College, Nellore, India
^*Manya Singh
Medicine, Sikkim Manipal Institute Of Medical Sciences, Gangtok, India
Abhishek L Hiremath
Medicine, Subbaiah Institute Of Medical Sciences And Research Centre, Shivamogga, India

^*Corresponding Author:

Manya Singh
Medicine, Sikkim Manipal Institute Of Medical Sciences, Gangtok, India

Published on: 2025-08-13

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

Keywords

Dietary fiber, Gut microbiota, Insulin resistance, Macronutrients, Metabolic health, Obesity, Type 2 diabetes

Introduction

Obesity and diabetes have become pervasive health concerns globally, with significant implications for public health and healthcare systems [1-3]. The rise in these conditions is primarily linked to modern lifestyle factors, including poor dietary habits, physical inactivity, and altered microbiota composition [4, 5]. Central to understanding and addressing these metabolic disorders is the interplay between macronutrients, gut microbiota, and the body’s metabolic responses [6- 8]. Growing body research has highlighted how the balance and quality of macronutrients proteins, fats, and carbohydrates can influence the development and progression of obesity and diabetes, underscoring the need for dietary strategies that target these metabolic pathways [9-11]. Furthermore, the gut microbiota, an intricate ecosystem of microorganisms residing in the intestines, plays a crucial role in regulating energy balance, glucose metabolism, and inflammation, all of which are implicated in these conditions [12, 13].

Recent studies have illuminated the complex relationship between diet and gut microbiota composition [14-16]. Certain dietary patterns can either promote or inhibit the growth of specific microbial populations, which in turn can modulate host metabolism. For example, high-fat diets (HFD), high-sugar (HS) diets have been shown to disrupt the diversity of gut microbiota, promoting an inflammatory state that exacerbates IR and adiposity [17, 18]. Conversely, diets rich in fiber, plant-based foods, and fermented products can foster healthy microbiota, enhance metabolic functions and reduce the risk of obesity and T2D [19, 20]. This evolving understanding of the gut microbiome’s role in metabolism presents an opportunity to develop more personalized and effective dietary interventions that focus on modifying the microbiota as a means of improving metabolic health [21-23].

Dietary strategies aimed at combating obesity and diabetes must, therefore, consider both macronutrient composition and its impact on the gut microbiota [24, 25]. While traditional dietary approaches emphasize calorie restriction and macronutrient balance, emerging evidence suggests that microbiota-targeted interventions, such as prebiotics, probiotics, and postbiotics, could offer significant benefits in managing metabolic diseases [26, 27]. This integrated approach, combining macronutrient optimization with microbiota modulation, holds promise for developing comprehensive dietary guidelines and treatments that not only address the symptoms of obesity and diabetes but also tackle their root causes at the metabolic and microbial level [28, 29]. As research in this field continues to evolve, the hope is to establish practical, evidence-based dietary strategies that can be implemented at both individual and population levels to reduce the global burden of these chronic conditions.

Obesity and T2D are escalating global health crises, significantly impacting socioeconomic burdens worldwide [30, 31]. These metabolic disorders are characterized by a cluster of complications, including IR, chronic low-grade inflammation, and dyslipidemia [32, 33]. The intricate interplay between dietary macronutrients, the gut microbiota, and host metabolism has emerged as a critical area of research, offering potential therapeutic avenues for managing and preventing these diseases [34, 35]. This article explores the current understanding of this relationship, highlighting how dietary strategies can be tailored to modulate the gut microbiota, improve metabolic health, and combat obesity and diabetes [36, 37].