Proteobacteria are a major phylum in the human gut microbiota, comprising many known human pathogens. This review highlights the role of Proteobacteria in both intestinal and extraintestinal diseases, suggesting they may serve as a microbial signature of disease. Increased abundance of Proteobacteria is observed in conditions such as metabolic disorders, inflammatory bowel disease, and possibly lung diseases like asthma and COPD. These conditions are often associated with inflammation, which is a core aspect of Proteobacteria-related diseases. The gut microbiota plays a crucial role in host health, including metabolism, nutrient synthesis, and immune function. Proteobacteria are among the most abundant phyla in the gut, and their presence is linked to various diseases. Factors such as diet, age, and antibiotic use influence the microbiota composition. Recent studies have shown that Proteobacteria may contribute to metabolic disorders through mechanisms involving lipopolysaccharides and endotoxemia. In inflammatory bowel disease, Proteobacteria are often increased, and their presence is associated with disease progression. In lung diseases, Proteobacteria have been found in higher abundance in patients with asthma and COPD, suggesting a potential role in these conditions. The gut-lung axis may also play a role in the development of these diseases. Research indicates that the microbiota can influence the gut-brain axis and may contribute to metabolic and inflammatory diseases. Fecal microbiota transplantation has shown promise in modulating the microbiota to improve health outcomes. Overall, Proteobacteria are overrepresented in several diseases, particularly those with an inflammatory phenotype. While causality is not yet proven, studies are ongoing to better understand the mechanisms linking dysbiosis and disease. The gut microbiome is an expanding area of research, with implications for the development of new therapeutic strategies.Proteobacteria are a major phylum in the human gut microbiota, comprising many known human pathogens. This review highlights the role of Proteobacteria in both intestinal and extraintestinal diseases, suggesting they may serve as a microbial signature of disease. Increased abundance of Proteobacteria is observed in conditions such as metabolic disorders, inflammatory bowel disease, and possibly lung diseases like asthma and COPD. These conditions are often associated with inflammation, which is a core aspect of Proteobacteria-related diseases. The gut microbiota plays a crucial role in host health, including metabolism, nutrient synthesis, and immune function. Proteobacteria are among the most abundant phyla in the gut, and their presence is linked to various diseases. Factors such as diet, age, and antibiotic use influence the microbiota composition. Recent studies have shown that Proteobacteria may contribute to metabolic disorders through mechanisms involving lipopolysaccharides and endotoxemia. In inflammatory bowel disease, Proteobacteria are often increased, and their presence is associated with disease progression. In lung diseases, Proteobacteria have been found in higher abundance in patients with asthma and COPD, suggesting a potential role in these conditions. The gut-lung axis may also play a role in the development of these diseases. Research indicates that the microbiota can influence the gut-brain axis and may contribute to metabolic and inflammatory diseases. Fecal microbiota transplantation has shown promise in modulating the microbiota to improve health outcomes. Overall, Proteobacteria are overrepresented in several diseases, particularly those with an inflammatory phenotype. While causality is not yet proven, studies are ongoing to better understand the mechanisms linking dysbiosis and disease. The gut microbiome is an expanding area of research, with implications for the development of new therapeutic strategies.