A novel fructan from Atractylodes macrocephala ameliorates ulcerative colitis through gut microbiota-mediated PI3K/Akt signaling.

Polysaccharides from edible and medicinal plants are promising natural agents for intestinal health. In this study, a homogeneous polysaccharide (AMP) was isolated from Atractylodes macrocephala Koidz. Structural characterization revealed that AMP (Mw = 3.56 kDa) primarily consisted of fructose (92.4 %) and glucose (7.6 %), with β-D-fructofuranose and α-d-glucopyranose residues linked through →1)-β-D-Fruf-(2→, →1,6)-β-D-Fruf-(2→, and α-D-Glcp-(1 → glycosidic bonds. In vivo studies confirmed the efficacy of AMP against ulcerative colitis (UC) in a DSS-induced mouse model, as evidenced by a significant improvement in disease symptoms, including increased body weight, longer colon length, and elevated goblet cell counts, coupled with a reduction in the disease activity index and histological damage. Mechanistically, AMP attenuated inflammation by restoring intestinal barrier integrity and regulating the gut microbiota to maintain its homeostasis. These regulatory effects were further validated through fecal microbiota transplantation (FMT) and antibiotic intervention (Abx). Olink proteomics and western blotting demonstrated that the ameliorative effect of AMP on UC, mediated via the PI3K/Akt pathway, was entirely dependent on the homeostasis of the gut microbiota. Collectively, these findings position AMP as a promising functional food ingredient or natural therapeutic for UC, providing a scientific basis for the high-value exploitation of A. macrocephala.