Colorectal cancer (CRC) is a malignant tumor that threatens human health worldwide. Disturbance of the gut microbiota caused by various external factors is one of the leading causes. Carnosic acid (CA) is a phenolic diterpene compound, mainly isolated from rosemary plants, with anti-inflammatory and anti-tumor properties. In this study, we aimed to investigate the role of CA in CRC development and its underlying mechanisms in B6/JGpt-Apc/Gpt (Apc) mice based on the analysis of gut microbiota, serum metabolomics, and tumor proteomics. Enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to confirm the changes in cytokine and protein levels related to inflammation after CA administration. CA regulated the abundance of the gut microbiota, which further caused changes in the production of dl-lactic acid. CA suppressed the inflammatory response by reducing the levels of IL-1β, -6, and -17A. Overall, CA showed anti-CRC properties via modulation of gut microbiota and serum metabolites through NF-κB/STAT3 signaling to inhibit IL-17 expression in Apc mice. These results provide experimental evidence for the future treatment of CRC with CA.
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