The human gut microbiota, comprising over 100 trillion microbial cells, plays a crucial role in metabolic regulation through symbiotic interactions with the host. Altered gut microbial ecosystems have been linked to increased metabolic and immune disorders in both animals and humans. The review discusses the molecular interactions between the gut microbiota and host energy metabolism, lipid accumulation, and immunity, focusing on the axis that links gut microbes and host metabolic inflammation. It also explores therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, highlighting the challenges in this area. The gut microbiota's role in obesity and metabolic diseases is complex, involving interactions with host physiology, energy metabolism, and immune pathways. Chronic inflammation, driven by microbial-derived metabolites and lipopolysaccharides (LPS), is a key factor in the development of these conditions. Probiotics and prebiotics have shown promise in modulating gut microbial ecology and improving metabolic health, but further research is needed to optimize their use. The review emphasizes the importance of integrating epidemiological data with animal studies to better understand the gut microbiota's role in obesity and to develop personalized healthcare strategies.The human gut microbiota, comprising over 100 trillion microbial cells, plays a crucial role in metabolic regulation through symbiotic interactions with the host. Altered gut microbial ecosystems have been linked to increased metabolic and immune disorders in both animals and humans. The review discusses the molecular interactions between the gut microbiota and host energy metabolism, lipid accumulation, and immunity, focusing on the axis that links gut microbes and host metabolic inflammation. It also explores therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, highlighting the challenges in this area. The gut microbiota's role in obesity and metabolic diseases is complex, involving interactions with host physiology, energy metabolism, and immune pathways. Chronic inflammation, driven by microbial-derived metabolites and lipopolysaccharides (LPS), is a key factor in the development of these conditions. Probiotics and prebiotics have shown promise in modulating gut microbial ecology and improving metabolic health, but further research is needed to optimize their use. The review emphasizes the importance of integrating epidemiological data with animal studies to better understand the gut microbiota's role in obesity and to develop personalized healthcare strategies.