Clostridioides difficile: A suspected pro-carcinogenic bacterium for gastrointestinal tumors

Gastrointestinal tumors are among the most prevalent and deadly cancers worldwide and have been increasingly associated with the gut microbiota. Particularly, colorectal cancer (CRC) has become a focal point for unraveling the complex interplay between microbial dynamics and gastrointestinal tumor development, as extensive studies have shown that gut microbiota dysbiosis is closely associated with CRC, affecting energy harvest, metabolism, and mucosal and systemic immune responses. Clostridioides difficile ( C. difficile ) is the major causative agent of gut microbiota dysbiosis, with toxins A and B being its main pathogenic factors. These toxins reportedly trigger a complex cascade of host cellular responses, leading to diarrhea, inflammation, and tissue necrosis. However, recent experimental evidence suggests that chronic infection with C. difficile is a previously unrecognized contributor to colonic tumorigenesis. In this concise review, we summarize the hypothetical models and provide a comprehensive overview of the mechanisms linking the microbiota to colorectal carcinogenesis, focusing on the reasonable extrapolation of the interaction between C. difficile and CRC. Understanding the significance of C. difficile as a potential pro-carcinogenic bacterium and its potential role as a biomarker in CRC is crucial for advancing our knowledge in preventing tumorigenesis, recurrence, and gastrointestinal tumor metastasis.