Abstract

The global rise in obesity-associated type 2 diabetes mellitus (T2DM) has sparked a paradigm shift in 
understanding metabolic diseases beyond mere caloric imbalance. Emerging evidence positions the gut 
microbiota as a critical modulator of host metabolism, immunity, and endocrine signaling. Alterations in gut 
microbial composition termed dysbiosis are intricately linked to chronic low-grade inflammation, insulin 
resistance, and lipid metabolism dysfunction, all of which are hallmarks of obesity-associated diabetes. 
Concurrently, natural products from plants, fungi, and marine sources have gained attention for their prebiotic, 
antimicrobial, and immunomodulatory properties that favorably reshape gut microbial ecology. This review 
examines the mechanistic pathways through which natural compounds modulate gut microbiota and attenuate 
metabolic dysregulation in obesity-associated T2DM. Specific focus is given to polyphenols, flavonoids, 
alkaloids, polysaccharides, and essential oils, highlighting their impact on microbial diversity, short-chain fatty 
acid production, intestinal barrier integrity, and inflammatory markers. We also explore clinical and 
translational implications, challenges in therapeutic implementation, and future directions for microbiota
targeted natural interventions in metabolic syndrome.