Fig. 4: Roles of intratumoral microbiota in HCC and other common tumors.

For example, Gammaproteobacteria was increased and could secrete cytolethal distending toxin (CDT) and thus cause significant dose-dependent DNA damage which may cause original HCC. Intratumoral microbiota has the potential to intervene in HCC progression by influencing the function of immune cells such as macrophages, T cells and MDSCs. Some downregulated intratumoral microbes might be protective microbes and were significantly positively correlated with some metabolites also decreased in HCC tissues. In lung cancer, gut-derived Akkermansia muciniphila migrated into the blood circulation and colonized local lung cancer tissue and then inhibited tumorigenesis mainly by modulating other intratumoral microbiota and activating lung-resident γδ T cells. In CRC, the intratumoral microbiota pks⁺ Escherichia and Bacteroides fragilis increased metastasis by destroying the gut–vascular barrier by the stimulation of IL-17 and DNA damage. Increased Fusobacterium nucleatum in CRC cells activated YAP signaling and downregulated the transcription factor forkhead box D3 (FOXD3), which reduced METTL3 transcription. This subsequently reduced the m⁶A levels of kinesin family member 26B (KIF26B) mRNA and thereby upregulated its expression and inhibited its degradation, which together contributed to CRC metastasis. Improved intratumor microbiota diversity in pancreatic cancer was modulated by the gut microbiota and increased survival due to increased cytotoxic T cells and decreased MDSCs.