The interaction between the microbiota and the immune system is crucial for maintaining health and preventing disease. The microbiome plays a key role in the development and function of the host's innate and adaptive immune systems, while the immune system helps maintain the balance of the host-microbe relationship. Imbalances in microbiota-immune interactions can lead to immune-mediated disorders. This review discusses the mechanisms of microbiome-immunity crosstalk in the gut and other organs, highlighting current knowledge, challenges, and future therapeutic strategies. The microbiota influences the development of the immune system, particularly in early life. The composition of the microbiota in the first few years of life is highly variable and plays a critical role in shaping immune responses. The absence of commensal microbes in germ-free animals leads to immune deficiencies, including reduced numbers of intra-epithelial lymphocytes and impaired IgA production. The microbiota also influences the development of regulatory T cells and Th17 cells, which are essential for immune homeostasis. In homeostasis, the intestinal microbiota is compartmentalized by the mucus layer and tight junctions, which prevent the translocation of harmful microbes. The innate immune system interacts with the microbiota through pattern recognition receptors (PRRs), such as TLRs and NODs, which recognize microbial signals and regulate immune responses. The microbiota also influences the function of dendritic cells, macrophages, and innate lymphoid cells, which are critical for maintaining immune balance. Environmental factors, such as antibiotics and diet, can disrupt the microbiota and lead to immune dysregulation. Antibiotic use can reduce microbial diversity and increase susceptibility to infections, while a Western-style diet can alter the gut microbiome and promote inflammation. These changes can contribute to the development of immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and cardiometabolic disorders. In IBD, dysbiosis of the gut microbiota is associated with increased inflammation and tissue damage. Mutations in genes such as NOD2 and ATG16L1 are linked to the development of Crohn's disease. The microbiota also plays a role in the pathogenesis of other diseases, including cancer, where certain bacteria can enhance tumor growth and reduce the effectiveness of immunotherapy. The interaction between the microbiota and the immune system extends beyond the gut, influencing the liver, brain, and lungs. Microbiome-derived metabolites, such as short-chain fatty acids, can modulate immune responses in these organs. The microbiota also influences the development of autoimmune diseases, such as rheumatoid arthritis, by promoting the production of pro-inflammatory cytokines. Understanding the complex interactions between the microbiota and the immune system is essential for developing new therapeutic strategies. Targeting the microbiome may offer promising approaches for treating immune-mediated diseases, including IBD, cancer, and autoimmune disorders. Further research is needed to fully understand the mechanisms underlying these interactionsThe interaction between the microbiota and the immune system is crucial for maintaining health and preventing disease. The microbiome plays a key role in the development and function of the host's innate and adaptive immune systems, while the immune system helps maintain the balance of the host-microbe relationship. Imbalances in microbiota-immune interactions can lead to immune-mediated disorders. This review discusses the mechanisms of microbiome-immunity crosstalk in the gut and other organs, highlighting current knowledge, challenges, and future therapeutic strategies. The microbiota influences the development of the immune system, particularly in early life. The composition of the microbiota in the first few years of life is highly variable and plays a critical role in shaping immune responses. The absence of commensal microbes in germ-free animals leads to immune deficiencies, including reduced numbers of intra-epithelial lymphocytes and impaired IgA production. The microbiota also influences the development of regulatory T cells and Th17 cells, which are essential for immune homeostasis. In homeostasis, the intestinal microbiota is compartmentalized by the mucus layer and tight junctions, which prevent the translocation of harmful microbes. The innate immune system interacts with the microbiota through pattern recognition receptors (PRRs), such as TLRs and NODs, which recognize microbial signals and regulate immune responses. The microbiota also influences the function of dendritic cells, macrophages, and innate lymphoid cells, which are critical for maintaining immune balance. Environmental factors, such as antibiotics and diet, can disrupt the microbiota and lead to immune dysregulation. Antibiotic use can reduce microbial diversity and increase susceptibility to infections, while a Western-style diet can alter the gut microbiome and promote inflammation. These changes can contribute to the development of immune-mediated diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis, and cardiometabolic disorders. In IBD, dysbiosis of the gut microbiota is associated with increased inflammation and tissue damage. Mutations in genes such as NOD2 and ATG16L1 are linked to the development of Crohn's disease. The microbiota also plays a role in the pathogenesis of other diseases, including cancer, where certain bacteria can enhance tumor growth and reduce the effectiveness of immunotherapy. The interaction between the microbiota and the immune system extends beyond the gut, influencing the liver, brain, and lungs. Microbiome-derived metabolites, such as short-chain fatty acids, can modulate immune responses in these organs. The microbiota also influences the development of autoimmune diseases, such as rheumatoid arthritis, by promoting the production of pro-inflammatory cytokines. Understanding the complex interactions between the microbiota and the immune system is essential for developing new therapeutic strategies. Targeting the microbiome may offer promising approaches for treating immune-mediated diseases, including IBD, cancer, and autoimmune disorders. Further research is needed to fully understand the mechanisms underlying these interactions