Abstract
In the mid-2000s, mouse studies suggested that the gut microbiome might influence energy harvest, fat storage, appetite, insulin sensitivity, and inflammation. Since then, our understanding of the gut microbiome's role in obesity has advanced significantly. Mechanistic studies identified microbial metabolites, such as short-chain fatty acids, bile acids, branched-chain amino acids, tryptophan catabolites, and imidazole propionate, as key modulators of metabolism, inflammation, and gut-brain communication. Metagenomic and multi-omics technologies now provide deeper insights into the intricate interactions between microbes, metabolites, and host factors, reshaping obesity research and reinforcing the need for phenotype stratification by recognizing microbiome-driven metabolic profiles. Integrating gut microbiome data into clinical strategies may enable targeted interventions for specific obesity subtypes, advancing prevention and personalized care. However, as new anti-obesity medications emerge, it is imperative to determine how microbiome-based therapies can complement them, considering efficacy, cost, and patient-specific variability.