Indole-3-lactic acid suppresses colorectal cancer via metabolic reprogramming

Colorectal cancer (CRC) is a common malignant neoplasm influenced by both genetic and environmental factors, and its incidence correlates with the composition of the gut microbiota. Relevant studies have demonstrated that gut microbiota dysbiosis is associated with CRC progression. However, the relationship between CRC tumor proliferation and dysregulation of tryptophan metabolism remains unclear. Our investigation addresses the role and mechanisms of amino acid metabolites in tumor progression based on the dysregulation of tryptophan metabolism in clinical CRC patients. Using metagenomic sequencing and targeted tryptophan metabolomics, our research delineates the aberrant levels of indole-3-lactic acid (ILA) in CRC patients. ILA inhibits glycolysis via the STAT3-HK2 axis and exerts a suppressive effect on CRC independent of the aryl hydrocarbon receptor (AHR). By elucidating the inhibitory role of ILA in CRC and uncovering its underlying mechanisms, our study provides a prospective therapeutic avenue for CRC treatment. Overall design: Co culture ILA (1mM) with HCT116 cells for 24 hours, with the same concentration of DMSO as the control. Observe the effect of ILA on mRNA expression in HCT116 cells.