Staphylococcus aureus (S. aureus) is a common pathogen causing various human diseases, including skin infections, food poisoning, endocarditis, and sepsis. These infections range from minor to life-threatening, requiring complex medical management and leading to significant healthcare costs. The intestinal microbiome, a critical component of human health, influences physiological functions and immune responses, but its interaction with S. aureus infections remains poorly understood. This review summarizes recent research on S. aureus infections and their interactions with the intestinal microbiome, highlighting the mechanisms involved and the challenges in prevention and treatment. S. aureus is a Gram-positive bacterium commonly found on the skin and in the nasal passages. While often harmless, it can cause severe infections, especially in individuals with compromised immune systems. The emergence of methicillin-resistant S. aureus (MRSA) has become a major clinical challenge. S. aureus infections trigger both innate and adaptive immune responses, involving various immune cells and signaling pathways. The bacterium can colonize the skin and other body sites, and its interaction with the microbiome can influence its pathogenicity. S. aureus infections, such as skin and soft-tissue infections (SSTIs), can range from mild to severe. They are often caused by antibiotic-resistant strains, including MRSA. SSTIs can lead to systemic infections like sepsis and endocarditis. The immune response to S. aureus involves the activation of immune cells and the production of cytokines and chemokines. S. aureus has developed strategies to evade the immune system, including the secretion of proteins that inhibit immune responses. Food poisoning caused by S. aureus is widespread and increasingly common. The bacterium produces enterotoxins that cause symptoms like vomiting and diarrhea. These toxins can trigger immune responses and affect the gut microbiome, leading to dysbiosis. The gut microbiome plays a crucial role in maintaining health and can influence the severity of S. aureus infections. S. aureus bacteremia (SAB) is a serious condition that can lead to sepsis and endocarditis. It is often associated with MRSA and has a high mortality rate. The pathogenesis of SAB involves the bacterium's ability to evade the immune system and cause systemic inflammation. The gut microbiome can influence the development of SAB by affecting the intestinal barrier and immune responses. Infective endocarditis (IE) caused by S. aureus is a severe condition, often associated with MRSA. The bacterium can colonize the heart valves and cause valve damage. The interaction between S. aureus and the gut microbiome can influence the progression of IE and the immune response. The gut microbiome is essential for maintaining health and can be disrupted by S. aureus infections. Dysbiosis in the gut can lead to increased susceptibility to S. aureus infections and affect the immune system. StrategiesStaphylococcus aureus (S. aureus) is a common pathogen causing various human diseases, including skin infections, food poisoning, endocarditis, and sepsis. These infections range from minor to life-threatening, requiring complex medical management and leading to significant healthcare costs. The intestinal microbiome, a critical component of human health, influences physiological functions and immune responses, but its interaction with S. aureus infections remains poorly understood. This review summarizes recent research on S. aureus infections and their interactions with the intestinal microbiome, highlighting the mechanisms involved and the challenges in prevention and treatment. S. aureus is a Gram-positive bacterium commonly found on the skin and in the nasal passages. While often harmless, it can cause severe infections, especially in individuals with compromised immune systems. The emergence of methicillin-resistant S. aureus (MRSA) has become a major clinical challenge. S. aureus infections trigger both innate and adaptive immune responses, involving various immune cells and signaling pathways. The bacterium can colonize the skin and other body sites, and its interaction with the microbiome can influence its pathogenicity. S. aureus infections, such as skin and soft-tissue infections (SSTIs), can range from mild to severe. They are often caused by antibiotic-resistant strains, including MRSA. SSTIs can lead to systemic infections like sepsis and endocarditis. The immune response to S. aureus involves the activation of immune cells and the production of cytokines and chemokines. S. aureus has developed strategies to evade the immune system, including the secretion of proteins that inhibit immune responses. Food poisoning caused by S. aureus is widespread and increasingly common. The bacterium produces enterotoxins that cause symptoms like vomiting and diarrhea. These toxins can trigger immune responses and affect the gut microbiome, leading to dysbiosis. The gut microbiome plays a crucial role in maintaining health and can influence the severity of S. aureus infections. S. aureus bacteremia (SAB) is a serious condition that can lead to sepsis and endocarditis. It is often associated with MRSA and has a high mortality rate. The pathogenesis of SAB involves the bacterium's ability to evade the immune system and cause systemic inflammation. The gut microbiome can influence the development of SAB by affecting the intestinal barrier and immune responses. Infective endocarditis (IE) caused by S. aureus is a severe condition, often associated with MRSA. The bacterium can colonize the heart valves and cause valve damage. The interaction between S. aureus and the gut microbiome can influence the progression of IE and the immune response. The gut microbiome is essential for maintaining health and can be disrupted by S. aureus infections. Dysbiosis in the gut can lead to increased susceptibility to S. aureus infections and affect the immune system. Strategies