Pithecellobium clypearia Benth and malic acid protect against colitis by enhancing intestinal epithelial fucosylation and barrier function.

[BACKGROUND] Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colonic mucosa, leading to abdominal pain, diarrhea, and increased risk of colorectal cancer. Pithecellobium clypearia Benth (P. clypearia), a traditional herbal medicine, has long been used to treat inflammatory and infectious diseases, yet its therapeutic potential and underlying mechanisms in UC remain unclear.

[METHODS] A DSS-induced colitis model was established in mice to evaluate the protective effects of aqueous P. clypearia extracts at different doses. Clinical parameters, histopathology, and mucus barrier integrity were assessed. Integrated transcriptomic, metabolomic, and 16S rRNA sequencing analyses were conducted to identify key pathways, metabolites, and microbiota changes. The activity of malic acid, a major organic acid component of P. clypearia, was further validated both in vivo and in vitro.

[RESULTS] Transcriptomic analysis revealed upregulation of fucosylation-related genes, including Fut2 and Fut9, which was consistent with enhanced epithelial glycosylation and improved integrity of the mucus barrier. Metabolomic profiling identified elevated levels of organic carboxylic acids, such as citramalic acid. These host responses were accompanied by a selective enrichment of mucin-associated bacteria, particularly Akkermansia, suggesting a potential interaction between epithelial remodeling and microbiota composition induced by P. clypearia. Notably, malic acid alone reproduced the protective effects of P. clypearia by inducing epithelial fucosylation, reinforcing barrier integrity, and modulating gut microbial communities.