Lactobacillus plantarum and its metabolite, indole-3-lactic acid ameliorates colorectal tumorigenesis through contributing to CD8+ T cell immunity via epigenetic regulation

Previous studies have shown that probiotics, the Lactobacillus species, play a role in ameliorating colorectal cancer (CRC) in a mouse model. However, the underlying mechanisms remain largely unknown. Here, we found that administration of the probiotic strain, Lactobacillus plantarum L168 (LP-L168) and its metabolite, indole-3-lactic acid (ILA) ameliorated intestinal inflammation, tumor growth, and gut dysbiosis. Mechanistically, we indicated that LP-L168/ILA treatment accelerated IL12a production in dendritic cells by enhancing H3K27ac binding at the enhancer regions of IL12a that contributed to priming CD8+T cell immunity against tumor growth. Furthermore, LP-L168/ILA were found to transcriptionally inhibit Saa3 expression related to cholesterol metabolism of CD8+T cells through changing chromatin accessibility and subsequent inhibiting of function of IFN-Gama+CD8+ T in tumor tissue. Together, our findings provide new insights into the epigenetic regulation of bacteria-mediated anti-tumor immunity and suggest the potential of LP-L168 to develop probiotic-based therapeutic strategies for CRC.