The human gut microbiota plays a crucial role in metabolic regulation through symbiotic interactions with the host. Alterations in gut microbial ecosystems are linked to metabolic and immune disorders. The review discusses the mechanisms linking gut microbiota, host energy metabolism, and the immune system in obesity and metabolic diseases, focusing on the gut-microbial-host-immune axis. It highlights the importance of the gut microbiota in regulating obesity and related pathologies through molecular interactions with energy metabolism and inflammation pathways. Therapeutic approaches to reshape the gut microbiota to prevent obesity-related diseases are explored, along with challenges in this area. The gut microbiota consists of trillions of microbes that influence immune and neurological development. Gene sequencing data show that the gut metagenome is involved in core functions such as digestion, immune system development, and host metabolism. The microbiota produces signaling molecules that interact with host metabolism, such as short-chain fatty acids (SCFAs) that affect insulin sensitivity. Changes in the gut ecosystem can disrupt microbial-host symbiosis, leading to metabolic disorders. Obesity is characterized by excess adipose tissue and is associated with metabolic syndrome, which includes conditions like hyperglycemia, hypertriglyceridemia, and hypertension. Insulin resistance, low-grade inflammation, and fat accumulation are key factors in the development of metabolic syndrome. The gut microbiota influences these processes through molecular interactions with energy metabolism and inflammation pathways. The gut microbiota affects calorie harvest and energy homeostasis by influencing gut epithelium development, polysaccharide digestion, and the expression of genes involved in lipid metabolism. SCFAs interact with GPCRs to modulate gut motility and host immunity. The microbiota also regulates fat deposition through the farnesoid X receptor (FXR) and bile acid metabolism. Shifts in the gut microbial ecosystem in obesity are influenced by diet and co-housing. Human studies show that obesity is associated with changes in the Bacteroidetes:Firmicutes ratio. The gut microbiota contributes to obesity through inflammation and altered microbial composition. Chronic inflammation links the gut microbiota to obesity and insulin resistance. Lipopolysaccharides (LPS) from Gram-negative bacteria trigger inflammatory responses, leading to metabolic endotoxemia. LPS activates inflammatory pathways, contributing to insulin resistance and obesity. Other microbial-derived metabolites, such as indole, interact with host signaling pathways and affect immunity. Indole-3-propionate improves gut barrier function and reduces inflammation. The gut microbiota affects host health through modulation of gut physiology, LPS infiltration, calorie intake, fat accumulation, and insulin action. Therapeutic approaches to manipulate the gut microbiota include fecal transplantation, probiotics, and prebiotics. These interventions can improve glucose metabolism, reduce inflammation, and modulate the gut microbiota. However, more research is needed to fully understand the mechanisms and effectiveness of these approaches. In conclusion, the gut microbiota plays a significant role inThe human gut microbiota plays a crucial role in metabolic regulation through symbiotic interactions with the host. Alterations in gut microbial ecosystems are linked to metabolic and immune disorders. The review discusses the mechanisms linking gut microbiota, host energy metabolism, and the immune system in obesity and metabolic diseases, focusing on the gut-microbial-host-immune axis. It highlights the importance of the gut microbiota in regulating obesity and related pathologies through molecular interactions with energy metabolism and inflammation pathways. Therapeutic approaches to reshape the gut microbiota to prevent obesity-related diseases are explored, along with challenges in this area. The gut microbiota consists of trillions of microbes that influence immune and neurological development. Gene sequencing data show that the gut metagenome is involved in core functions such as digestion, immune system development, and host metabolism. The microbiota produces signaling molecules that interact with host metabolism, such as short-chain fatty acids (SCFAs) that affect insulin sensitivity. Changes in the gut ecosystem can disrupt microbial-host symbiosis, leading to metabolic disorders. Obesity is characterized by excess adipose tissue and is associated with metabolic syndrome, which includes conditions like hyperglycemia, hypertriglyceridemia, and hypertension. Insulin resistance, low-grade inflammation, and fat accumulation are key factors in the development of metabolic syndrome. The gut microbiota influences these processes through molecular interactions with energy metabolism and inflammation pathways. The gut microbiota affects calorie harvest and energy homeostasis by influencing gut epithelium development, polysaccharide digestion, and the expression of genes involved in lipid metabolism. SCFAs interact with GPCRs to modulate gut motility and host immunity. The microbiota also regulates fat deposition through the farnesoid X receptor (FXR) and bile acid metabolism. Shifts in the gut microbial ecosystem in obesity are influenced by diet and co-housing. Human studies show that obesity is associated with changes in the Bacteroidetes:Firmicutes ratio. The gut microbiota contributes to obesity through inflammation and altered microbial composition. Chronic inflammation links the gut microbiota to obesity and insulin resistance. Lipopolysaccharides (LPS) from Gram-negative bacteria trigger inflammatory responses, leading to metabolic endotoxemia. LPS activates inflammatory pathways, contributing to insulin resistance and obesity. Other microbial-derived metabolites, such as indole, interact with host signaling pathways and affect immunity. Indole-3-propionate improves gut barrier function and reduces inflammation. The gut microbiota affects host health through modulation of gut physiology, LPS infiltration, calorie intake, fat accumulation, and insulin action. Therapeutic approaches to manipulate the gut microbiota include fecal transplantation, probiotics, and prebiotics. These interventions can improve glucose metabolism, reduce inflammation, and modulate the gut microbiota. However, more research is needed to fully understand the mechanisms and effectiveness of these approaches. In conclusion, the gut microbiota plays a significant role in