The gut microbiota plays a crucial role in immune system development and function, influencing immune homeostasis and susceptibility to diseases. Advances in technology allow researchers to study the microbiome's composition and function, revealing how microbial metabolites and components shape the host immune system. The gut microbiota is highly diverse and dynamic, with distinct microbial communities in different body habitats. The microbiome's metabolic activity is essential for immune system development and function, and its disruption can lead to dysbiosis, which is linked to various diseases. Short-chain fatty acids (SCFAs), produced by microbial fermentation, are important for immune regulation. SCFAs inhibit histone deacetylases (HDACs), promoting a tolerogenic, anti-inflammatory environment. They also modulate T regulatory cells, enhancing immune suppression and reducing inflammation. SCFAs interact with G protein-coupled receptors (GPCRs) such as GPR43 and GPR109A, influencing immune responses and host defense. Additionally, SCFAs strengthen the intestinal epithelial barrier, preventing pathogen translocation and modulating immune cell function. AHR ligands, derived from gut microbiota, regulate immune responses and mucosal immunity. AHR activation is essential for immune cell development and function, and its deficiency can lead to immune dysregulation. Polyamines, produced by both host and microbes, are critical for cell growth and immune function. Dysregulated polyamine levels are linked to disease, and their modulation can influence immune responses and cancer development. Microbial components, such as polysaccharide A (PSA), formyl peptides, and HBP, interact with host pattern recognition receptors (PRRs) to trigger immune responses. These interactions are vital for maintaining immune homeostasis and defending against pathogens. Understanding these interactions provides insights into the complex host-microbiota relationship and offers potential therapeutic strategies for immune-related diseases. The study of microbial metabolites and components is essential for developing new treatments and understanding the role of the microbiome in health and disease.The gut microbiota plays a crucial role in immune system development and function, influencing immune homeostasis and susceptibility to diseases. Advances in technology allow researchers to study the microbiome's composition and function, revealing how microbial metabolites and components shape the host immune system. The gut microbiota is highly diverse and dynamic, with distinct microbial communities in different body habitats. The microbiome's metabolic activity is essential for immune system development and function, and its disruption can lead to dysbiosis, which is linked to various diseases. Short-chain fatty acids (SCFAs), produced by microbial fermentation, are important for immune regulation. SCFAs inhibit histone deacetylases (HDACs), promoting a tolerogenic, anti-inflammatory environment. They also modulate T regulatory cells, enhancing immune suppression and reducing inflammation. SCFAs interact with G protein-coupled receptors (GPCRs) such as GPR43 and GPR109A, influencing immune responses and host defense. Additionally, SCFAs strengthen the intestinal epithelial barrier, preventing pathogen translocation and modulating immune cell function. AHR ligands, derived from gut microbiota, regulate immune responses and mucosal immunity. AHR activation is essential for immune cell development and function, and its deficiency can lead to immune dysregulation. Polyamines, produced by both host and microbes, are critical for cell growth and immune function. Dysregulated polyamine levels are linked to disease, and their modulation can influence immune responses and cancer development. Microbial components, such as polysaccharide A (PSA), formyl peptides, and HBP, interact with host pattern recognition receptors (PRRs) to trigger immune responses. These interactions are vital for maintaining immune homeostasis and defending against pathogens. Understanding these interactions provides insights into the complex host-microbiota relationship and offers potential therapeutic strategies for immune-related diseases. The study of microbial metabolites and components is essential for developing new treatments and understanding the role of the microbiome in health and disease.