Lactobacillus plantarum-derived indole-3-lactic acid ameliorates colorectal tumorigenesis via epigenetic regulation of CD8+ T cell immunity

Cell Metab. 2023 Jun 6;35(6):943-960.e9. doi: 10.1016/j.cmet.2023.04.015. Epub 2023 May 15.


Previous studies have shown that 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 a probiotic strain, Lactobacillus plantarum L168 and its metabolite, indole-3-lactic acid, ameliorated intestinal inflammation, tumor growth, and gut dysbiosis. Mechanistically, we indicated that indole-3-lactic acid 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, indole-3-lactic acid was found to transcriptionally inhibit Saa3 expression related to cholesterol metabolism of CD8+ T cells through changing chromatin accessibility and subsequent enhancing function of tumor-infiltrating CD8+ T cells. Together, our findings provide new insights into the epigenetic regulation of probiotics-mediated anti-tumor immunity and suggest the potential of L. plantarum L168 and indole-3-lactic acid to develop therapeutic strategies for patients with CRC.

Keywords: ILA; Lactobacillus plantarum; colorectal cancer; epigenetic regulation; indole-3-lactic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Carcinogenesis
  • Colorectal Neoplasms*
  • Epigenesis, Genetic
  • Lactobacillus plantarum* / physiology
  • Mice


  • indole-3-lactic acid