Colorectal cancer (CRC) is a multistage and highly heterogeneous malignant disease that mostly occurred in aged people accompanied by microbiota alteration. Emerging evidence has uncovered the role of bacterial microbiota in the initiation and development of CRC. However, the effects of nonbacterial members inhabiting the human body, such as fungi, archaea, and viruses, have been largely ignored. The multi‐kingdom microbiota can be altered by dietary exposures and probiotic supplements. Furthermore, the efficacy of antitumor therapeutic strategies, such as radiotherapy, chemotherapy, and immunotherapy, are also closely associated with the alteration of multi‐kingdom microbiota. In this review, we describe CRC‐associated multi‐kingdom microbiota dysbiosis and the role of daily diet on CRC progression through microbiota alteration. We then discuss the impact of microbiota in different CRC therapies and highlight the advances as well as challenges in understanding how multi‐kingdom microbiome impacts the outcome of CRC.
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