The colonic mucosa has a complex interaction and is likely the most effective barrier against the numerically more superior microbial community within the gut microbiota. Therefore, it is probably not surprising that colorectal cancer (CRC), one of the largest challenges in gastroenterology and oncology, may be triggered and modulated by gut-microbial interactions more than many other diseases. Intense effort has been made to uncover the host:microbial interplay and provide simple, population-applicable and effective tools in the prevention of CRC with substantial scientific advances are made over the past year. As part of the series Year in Microbiota, this review provides comprehensive overview on the published literature between April 2021 and March 2022 in the area of CRC and the microbiota with potential highest impact in basic and translational research. This work includes studies on characterization of microbial alterations in CRC, functional models of microbiota in CRC, gut-immune system interaction and provides some summary on preventive and therapeutic knowledge.