Molecular docking, Western blot validation and <i>vitro</i> cell experiments confirmed that ASP and its regulated metabolites could inhibit the activity of PLA2/TLR4/MyD88/NF-κB signaling pathway.<h4>Conclusion</h4>The results indicate that anti-CRC effect of ASP may be jointly regulated through multiple pathways: correcting abnormal glycerophospholipid and tryptophan metabolism in the host, restoring the homeostasis of the intestinal microbiota, increase the content of some SCFAs, and inhibiting the TLR4/NF-κB signaling pathway. Here, TLR4 is linked to colorectal carcinoma.