Model systems to study tumor-microbiome interactions in early-onset colorectal cancer

Colorectal cancer (CRC) is a major health problem, with an alarming increase of early-onset CRC (EO-CRC) cases among individuals under 50 years of age. This trend shows the urgent need for understanding the underlying mechanisms leading to EO-CRC development and progression. There is significant evidence that the gut microbiome acts as a key player in CRC by triggering molecular changes in the colon epithelium, leading to tumorigenesis. However, a comprehensive collection and comparison of methods to study such tumor-microbiome interactions in the context of EO-CRC is sparse. This review provides an overview of the available in vivo, ex vivo as well as in vitro approaches to model EO-CRC and assess the effect of gut microbes on tumor development and growth. By comparing the advantages and limitations of each model system, it highlights that, while no single model is perfect, each is suitable for studying specific aspects of microbiome-induced tumorigenesis. Taken together, multifaceted approaches can simulate the human body's complexity, aiding in the development of effective treatment and prevention strategies for EO-CRC.