The Gut Microbiome in Human Obesity: A Comprehensive Review.

An estimated 2.6 billion individuals are currently living with overweight or obesity, and this number is projected to exceed 4 billion by 2035. Consequently, unless this increasing trajectory is effectively addressed, the trend is expected to continue in the coming years. The gut microbiome has emerged as a central regulator of host metabolism and energy homeostasis, making its detailed characterization crucial for the advancement of innovative therapeutic strategies and for elucidating mechanisms underlying metabolic health and disease. This review examines human obesity through the lens of the gut microbiome, providing a comprehensive overview of its role by addressing gut microbiome alterations, microbiome-driven mechanisms, dietary influences, prebiotic effects, microbiome-based therapeutics, and other approaches in the treatment of obesity and related metabolic disorders. The composition of the gut microbiome is altered in obesity and characterized by reduced microbial diversity and inconsistent shifts in dominant bacterial phyla, which collectively contribute to metabolic dysregulation. The gut microbiome influences obesity through multiple mechanisms. These include regulating energy balance and insulin sensitivity via short-chain fatty acids, inducing chronic inflammation, modulating metabolic and appetite genes, altering bile acid signaling, and promoting fat storage by inhibiting fasting-induced adipose factor. Dietary patterns exert a profound influence on gut microbiome composition and function, with plant-based diets conferring protective effects against obesity and its comorbidities. Microbiome-based therapeutics, including probiotics, synbiotics, and fecal microbiota transplantation, have demonstrated potential in modulating key metabolic and inflammatory pathways associated with obesity. As the scientific understanding of the human gut microbiome continues to advance, the integration of microbiome-based therapies into standard clinical practice is poised to become increasingly feasible and therapeutically transformative, particularly for obesity, a complex condition that demands innovative and customized interventions.