Remodeling the gut ecosystem and its mechanism: Natural products in the treatment of ulcerative colitis via regulating gut microbiota and metabolites.

Ulcerative colitis (UC) is a chronic intestinal disease with an unclear pathogenesis and a rising global incidence. Currently available medications and surgeries for UC carry side effects and potential clinical risks. Natural products, characterized by their multi-target mechanisms and low toxicity, show promising potential for UC treatment. However, the mechanisms underlying their therapeutic effects remain insufficiently understood. This review elucidates the mechanisms by which six major classes of natural products (including alkaloids, polysaccharides, polyphenols, glycosides, terpenoids, and a few animal-derived compounds) alleviate colitis. These natural products exert anti-UC effects primarily by modulating the gut microbiota and related metabolic pathways, such as the production of short-chain fatty acids (SCFAs), tryptophan (Trp), and bile acids (BAs), thereby restoring intestinal barrier function, maintaining immune homeostasis, and inhibiting inflammatory signaling pathways (e.g., NF-κB, Notch, MAPK). Furthermore, we summarize recent advances in cutting-edge technologies for identifying and validating the therapeutic targets of natural products (such as single-cell transcriptomics, spatial transcriptomics, and cellular thermal shift assay), and propose improved research ideas and strategies. These insights will facilitate the exploration of natural product targets and accelerate the development of targeted therapies and drugs for UC.