Significance of Fibrosis in Colorectal Cancer and Involvement of Gut Microbes

Gut microbes are one of the essential components of the tumor microenvironment, the same as interstitial stroma, angiogenesis, and immunity. With the advancement of technology, it has become possible to analyze various bacterial flora without culturing microbiomes comprehensively. There are a massive amount of gut microbes in the large intestine compared with other organs. It has been reported that some species of gut microbes, such as Fusobacterium nucleatum, are involved in the progression and metastasis of colorectal cancer and resistance to chemotherapy, with multiple mechanisms. The interstitial stroma composed of an extracellular matrix is also one of the crucial components of the tumor microenvironment involved in cancer progression and metastasis. It has been reported that fibrosis in the invasive front of the primary tumor and metastatic lymph nodes is a poor prognostic factor in colorectal cancer. Gut microbes affect not only cancer cells but also various surrounding factors such as fibrosis and angiogenesis. Gut microbes produced many kinds of enzymes, including protease, elastase, and collagenase, which degrade the surrounding extracellular matrix and secreted cytokines to induce inflammation and remodel a cancer-specific environment. It is important to consider the cancer microenvironment, including gut microbes and interstitial stroma, for treating colorectal cancer.