The gut microbiota plays a crucial role in tumor development, host immunity, and immunotherapy. Recent studies have shown that gut microbiota can influence tumor growth through dysbiosis, bacterial toxins, and modulation of host signaling pathways and immune status. Immune checkpoint inhibitors (ICIs) have significantly improved cancer treatment by enhancing immune cell responses. Current research indicates that gut microbiota and its metabolites can enhance immunotherapy effectiveness. Certain gut microbiota can serve as biomarkers for predicting immunotherapy responses. Interventions targeting the gut microbiota, such as fecal microbiota transplantation, probiotics, prebiotics, engineered bacteria, and dietary interventions, can improve ICI efficacy and enhance immunotherapy outcomes. This review discusses the role of gut microbiota and its metabolites in tumors, host immunity, and immunotherapy. It also reviews ongoing clinical trials aiming to manipulate the gut microbiota to enhance ICI efficacy and develop therapeutic strategies to reduce adverse effects. The gut microbiota influences tumor progression through its metabolites, genotoxins, and signaling pathways. It also affects immune responses, including innate and adaptive immunity, by modulating T-cell function and cytokine production. The gut microbiota can promote tumor immune activation or escape by altering the tumor microenvironment. It also contributes to the development of various diseases, including cancer. The gut microbiota forms the largest co-ecosystem with the host, interacting with host genes to modulate growth processes and adapt to environmental exposures. It plays a vital role in maintaining systemic immune homeostasis during bacterial infections and is integral to various immune processes. The intestinal mucosal immune system consists of lymph nodes, lamina propria, and epithelial cells, serving as a protective barrier for intestinal integrity. When the barrier is compromised, it can lead to various diseases, including inflammatory bowel disease and infections. The mucosal immune system monitors the composition of the gut microbiota. Inflammation caused by abnormalities in the immune system affects the balance of the intestinal microbiota and can lead to intestinal-associated diseases such as Crohn's disease and ulcerative colitis. The gut microbiota also influences the development of other digestive tumors, including hepatocellular carcinoma and pancreatic cancer. It can affect the progression of non-digestive tumors, such as breast cancer. The gut microbiota's metabolites, such as short-chain fatty acids (SCFAs) and bile acids, play a significant role in immunomodulation. SCFAs regulate T-cell metabolism and promote the differentiation of regulatory T (Treg) cells, which are important for maintaining immune homeostasis. Bile acids can influence the composition of the microbiota and affect the size and composition of the bile acid pool. The gut microbiota also interacts with the immune system, influencing innate and adaptive immunity. It can promote the development of immune-related disorders such as inflammatory bowel disease and cancer. The gut microbiota plays a critical role in the development and maturation ofThe gut microbiota plays a crucial role in tumor development, host immunity, and immunotherapy. Recent studies have shown that gut microbiota can influence tumor growth through dysbiosis, bacterial toxins, and modulation of host signaling pathways and immune status. Immune checkpoint inhibitors (ICIs) have significantly improved cancer treatment by enhancing immune cell responses. Current research indicates that gut microbiota and its metabolites can enhance immunotherapy effectiveness. Certain gut microbiota can serve as biomarkers for predicting immunotherapy responses. Interventions targeting the gut microbiota, such as fecal microbiota transplantation, probiotics, prebiotics, engineered bacteria, and dietary interventions, can improve ICI efficacy and enhance immunotherapy outcomes. This review discusses the role of gut microbiota and its metabolites in tumors, host immunity, and immunotherapy. It also reviews ongoing clinical trials aiming to manipulate the gut microbiota to enhance ICI efficacy and develop therapeutic strategies to reduce adverse effects. The gut microbiota influences tumor progression through its metabolites, genotoxins, and signaling pathways. It also affects immune responses, including innate and adaptive immunity, by modulating T-cell function and cytokine production. The gut microbiota can promote tumor immune activation or escape by altering the tumor microenvironment. It also contributes to the development of various diseases, including cancer. The gut microbiota forms the largest co-ecosystem with the host, interacting with host genes to modulate growth processes and adapt to environmental exposures. It plays a vital role in maintaining systemic immune homeostasis during bacterial infections and is integral to various immune processes. The intestinal mucosal immune system consists of lymph nodes, lamina propria, and epithelial cells, serving as a protective barrier for intestinal integrity. When the barrier is compromised, it can lead to various diseases, including inflammatory bowel disease and infections. The mucosal immune system monitors the composition of the gut microbiota. Inflammation caused by abnormalities in the immune system affects the balance of the intestinal microbiota and can lead to intestinal-associated diseases such as Crohn's disease and ulcerative colitis. The gut microbiota also influences the development of other digestive tumors, including hepatocellular carcinoma and pancreatic cancer. It can affect the progression of non-digestive tumors, such as breast cancer. The gut microbiota's metabolites, such as short-chain fatty acids (SCFAs) and bile acids, play a significant role in immunomodulation. SCFAs regulate T-cell metabolism and promote the differentiation of regulatory T (Treg) cells, which are important for maintaining immune homeostasis. Bile acids can influence the composition of the microbiota and affect the size and composition of the bile acid pool. The gut microbiota also interacts with the immune system, influencing innate and adaptive immunity. It can promote the development of immune-related disorders such as inflammatory bowel disease and cancer. The gut microbiota plays a critical role in the development and maturation of