The gut microbiome is a critical component of host health, influencing various physiological processes and diseases. Recent advancements in molecular techniques have revealed complex interactions between the gut microbiota and the host, linking microbial deviations to conditions such as obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases, and cancer. This review focuses on the molecular mechanisms by which gut bacteria influence health, emphasizing the role of metabolites like short-chain fatty acids (SCFAs), bile acids, and endocannabinoids, as well as their receptors such as PPARα, PPARγ, AhR, and G protein-coupled receptors (GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5). The gut microbiome's impact on metabolic disorders, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease, is discussed, highlighting the role of SCFAs in regulating energy homeostasis, glucose and lipid metabolism, and inflammation. Additionally, the review explores the role of lipopolysaccharides and pathogen-associated molecular patterns (PAMPs) in immune responses and the endocannabinoid system in modulating gut barrier function and metabolic disorders. The chapter also delves into the significance of bioactive lipids, bile acids, and the aryl hydrocarbon receptor (AhR) in energy metabolism, inflammation, and gut microbiome interactions. Finally, it discusses novel molecules like enterosynes, which modulate duodenal contraction and glucose metabolism, and their potential therapeutic applications.The gut microbiome is a critical component of host health, influencing various physiological processes and diseases. Recent advancements in molecular techniques have revealed complex interactions between the gut microbiota and the host, linking microbial deviations to conditions such as obesity, type 2 diabetes, hepatic steatosis, intestinal bowel diseases, and cancer. This review focuses on the molecular mechanisms by which gut bacteria influence health, emphasizing the role of metabolites like short-chain fatty acids (SCFAs), bile acids, and endocannabinoids, as well as their receptors such as PPARα, PPARγ, AhR, and G protein-coupled receptors (GPR41, GPR43, GPR119, Takeda G protein-coupled receptor 5). The gut microbiome's impact on metabolic disorders, including obesity, type 2 diabetes, and non-alcoholic fatty liver disease, is discussed, highlighting the role of SCFAs in regulating energy homeostasis, glucose and lipid metabolism, and inflammation. Additionally, the review explores the role of lipopolysaccharides and pathogen-associated molecular patterns (PAMPs) in immune responses and the endocannabinoid system in modulating gut barrier function and metabolic disorders. The chapter also delves into the significance of bioactive lipids, bile acids, and the aryl hydrocarbon receptor (AhR) in energy metabolism, inflammation, and gut microbiome interactions. Finally, it discusses novel molecules like enterosynes, which modulate duodenal contraction and glucose metabolism, and their potential therapeutic applications.