The "keystone pathogen" hypothesis proposes that certain low-abundance microbial pathogens can disrupt the balance of the microbiota, leading to inflammatory disease. This concept is supported by evidence from studies in animal models, including periodontitis, inflammatory bowel disease (IBD), colon cancer, and obesity. Keystone pathogens, such as Porphyromonas gingivalis in periodontitis and Klebsiella pneumoniae and Proteus mirabilis in IBD, can alter the microbiota composition and trigger inflammation, even when present in low abundance. These pathogens may also influence the host's immune response, leading to dysbiosis and disease. In colon cancer, certain bacteria, such as Bacteroides fragilis, may act as keystone pathogens by promoting carcinogenesis through interactions with the microbiota. Methanogens, though low in abundance, play a significant role in gut microbial communities by influencing energy metabolism and potentially contributing to host adiposity. The identification of keystone pathogens could lead to targeted therapies for complex dysbiotic diseases. The concept of keystone pathogens is consistent with observations in various animal models and highlights the importance of understanding microbial interactions in health and disease. Further research is needed to clarify the mechanisms by which keystone pathogens influence the microbiota and host homeostasis.The "keystone pathogen" hypothesis proposes that certain low-abundance microbial pathogens can disrupt the balance of the microbiota, leading to inflammatory disease. This concept is supported by evidence from studies in animal models, including periodontitis, inflammatory bowel disease (IBD), colon cancer, and obesity. Keystone pathogens, such as Porphyromonas gingivalis in periodontitis and Klebsiella pneumoniae and Proteus mirabilis in IBD, can alter the microbiota composition and trigger inflammation, even when present in low abundance. These pathogens may also influence the host's immune response, leading to dysbiosis and disease. In colon cancer, certain bacteria, such as Bacteroides fragilis, may act as keystone pathogens by promoting carcinogenesis through interactions with the microbiota. Methanogens, though low in abundance, play a significant role in gut microbial communities by influencing energy metabolism and potentially contributing to host adiposity. The identification of keystone pathogens could lead to targeted therapies for complex dysbiotic diseases. The concept of keystone pathogens is consistent with observations in various animal models and highlights the importance of understanding microbial interactions in health and disease. Further research is needed to clarify the mechanisms by which keystone pathogens influence the microbiota and host homeostasis.