Microbiota-driven immunometabolic regulation in colorectal cancer: Mechanisms and therapeutic opportunities

Figure 5 The impact of gut microbiota metabolites on immunometabolism and the tumor microenvironment in colorectal cancer. This diagram systematically illustrates the impact of six major metabolites of the gut microbiota on immune cells and the tumor microenvironment. Among them, short-chain fatty acids can, on the one hand, promote the killing effect of T cells and inhibit Tregs cells, thereby suppressing the development of colorectal cancer (CRC); on the other hand, they can induce the polarization of M2 macrophages to promote the progression of CRC. Tryptophan metabolites represented by kynurenine can inhibit the activity of CD8⁺ T cells. Polyamine metabolites are related to the apoptosis of CRC cells, and their deficiency often indicates the formation of an immunosuppressive microenvironment. Secondary bile acids such as lithocholic acid and deoxycholic acid can induce the development of CRC by directly damaging DNA, inducing oxidative stress, and promoting epithelial-mesenchymal transition. Lipopolysaccharides promote the progression of CRC by inducing pro-inflammatory responses, while H₂S affects the metabolism of normal intestinal epithelial cells by influencing mitochondrial function, thereby affecting the development of CRC. This Figure was drawn by Figdraw (Supplementary material). SCFA: Short-chain fatty acid; OXPHOS: Oxidative phosphorylation; IL: Interleukin; TNF-α: Tumor necrosis factor alpha; CRC: Colorectal cancer; LPS: Lipopolysaccharides; AhR: Aryl hydrocarbon receptor; IPA: Indolepropionic acid; LCA: Lithocholic acid; DCA: Deoxycholic acid; EMT: Epithelial-mesenchymal transition; VM: Vasculogenic mimicry; UDCA: Ursodeoxycholic acid.