This review article, authored by G. Rizzatti, L. R. Lopetuso, G. Gibiino, C. Binda, and A. Gasbarrini, focuses on the role of Proteobacteria in both intestinal and extraintestinal diseases. Proteobacteria, one of the most abundant phyla in the human gut microbiota, are known for their association with various human pathogens. The authors highlight recent findings that suggest Proteobacteria may serve as a microbial signature of disease, particularly in metabolic disorders and inflammatory bowel disease (IBD). Studies have shown increased abundance of Proteobacteria in conditions such as type 2 diabetes, obesity, nonalcoholic steatohepatitis, and cardiovascular diseases. In IBD, Proteobacteria are often found to be elevated, contributing to the inflammatory phenotype. Additionally, Proteobacteria have been implicated in lung diseases like asthma and chronic obstructive pulmonary disease (COPD), with higher abundance observed in these conditions. The review also discusses the potential mechanisms underlying these associations, including the role of lipopolysaccharides, endotoxemia, and the gut-brain axis. Finally, the authors emphasize the importance of further research to understand the complex interactions between Proteobacteria and disease, and the potential therapeutic benefits of modulating the gut microbiota.This review article, authored by G. Rizzatti, L. R. Lopetuso, G. Gibiino, C. Binda, and A. Gasbarrini, focuses on the role of Proteobacteria in both intestinal and extraintestinal diseases. Proteobacteria, one of the most abundant phyla in the human gut microbiota, are known for their association with various human pathogens. The authors highlight recent findings that suggest Proteobacteria may serve as a microbial signature of disease, particularly in metabolic disorders and inflammatory bowel disease (IBD). Studies have shown increased abundance of Proteobacteria in conditions such as type 2 diabetes, obesity, nonalcoholic steatohepatitis, and cardiovascular diseases. In IBD, Proteobacteria are often found to be elevated, contributing to the inflammatory phenotype. Additionally, Proteobacteria have been implicated in lung diseases like asthma and chronic obstructive pulmonary disease (COPD), with higher abundance observed in these conditions. The review also discusses the potential mechanisms underlying these associations, including the role of lipopolysaccharides, endotoxemia, and the gut-brain axis. Finally, the authors emphasize the importance of further research to understand the complex interactions between Proteobacteria and disease, and the potential therapeutic benefits of modulating the gut microbiota.