Staphylococcus aureus (S. aureus) is a common pathogen that can cause a range of human diseases, from minor skin infections to life-threatening conditions such as bacteremia and endocarditis. The intestinal microbiome, often referred to as the "forgotten organ," plays a crucial role in maintaining physiological health and can significantly impact both gastrointestinal diseases and disorders beyond the gut. However, the relationship between S. aureus infections and intestinal microbial homeostasis is not well understood. This review summarizes recent progress in understanding the interactions between S. aureus infections and the intestinal microbiome, highlighting the mechanisms behind these interactions and the challenges in preventing and treating S. aureus infections. The review also discusses the potential therapeutic strategies, such as maintaining gut microbial homeostasis through prebiotics, bacterial peptides, or fecal microbiota transplantation (FMT), to limit susceptibility to S. aureus infections. Additionally, it explores the impact of S. aureus infections on the intestinal microbial community, including changes in microbial diversity and abundance, and the potential role of short-chain fatty acids (SCFAs) in modulating these infections.Staphylococcus aureus (S. aureus) is a common pathogen that can cause a range of human diseases, from minor skin infections to life-threatening conditions such as bacteremia and endocarditis. The intestinal microbiome, often referred to as the "forgotten organ," plays a crucial role in maintaining physiological health and can significantly impact both gastrointestinal diseases and disorders beyond the gut. However, the relationship between S. aureus infections and intestinal microbial homeostasis is not well understood. This review summarizes recent progress in understanding the interactions between S. aureus infections and the intestinal microbiome, highlighting the mechanisms behind these interactions and the challenges in preventing and treating S. aureus infections. The review also discusses the potential therapeutic strategies, such as maintaining gut microbial homeostasis through prebiotics, bacterial peptides, or fecal microbiota transplantation (FMT), to limit susceptibility to S. aureus infections. Additionally, it explores the impact of S. aureus infections on the intestinal microbial community, including changes in microbial diversity and abundance, and the potential role of short-chain fatty acids (SCFAs) in modulating these infections.