Mechanistic analyses reveal that PA and LPS co-stimulation activates the IDO1-AhR-PI3K/Akt-NF-κB pathway, which is implicated in CRC progression.<h4>Conclusions</h4>These findings suggest that saturated fatty acids, particularly PA, may exacerbate CRC development risk through metabolic dysregulation, highlighting the potential of IDO1 as a biomarker for CRC associated with HFD. Here, AKT1 is linked to colorectal carcinoma.