A team led by clinicians and engineers has wrapped the plant-derived polyphenol pterostilbene (PSB) into prebiotic alginate/resistant-starch microcapsules coated with chitosan and shown that oral administration dampens dextran-sulfate-sodium (DSS) colitis in mice. The work, released online in Engineering, demonstrates that the 200-μm spheres escape gastric breakdown, accumulate in the colon for at least 12 h, and simultaneously curb inflammation, oxidative stress and dysbiosis while activating the aryl-hydrocarbon-receptor/interleukin-22 (AHR/IL-22) axis.

Investigators fabricated PSB-loaded microcapsules (PSB@MC) by micro-fluidic electrospray: a 2% alginate 2% resistant-starch suspension containing 0.6% PSB was dripped into 3% CaCl₂ to ionically cross-link the core, followed by a 1% chitosan acetate bath that electrostatically deposited a shell. Scanning electron micrographs revealed a wrinkled surface that, according to in-vivo imaging of cyanine-labelled spheres, doubled colonic fluorescence retention versus empty carriers in both healthy and DSS-exposed mice. Less than 40% of the cargo was released at pH 1.2 within 2 h, whereas simulated colonic fluid achieved complete discharge by 5 h, confirming pH-responsive behaviour.

In a preventive protocol, animals received 100 mg/kg PSB@MC every other day during seven-day 2.5% DSS exposure. The formulation limited weight loss, held the disease-activity index below 2 and reduced splenic index versus DSS controls. Histology showed intact crypts and fewer infiltrating leukocytes, while qPCR quantified significant down-regulation of TNF-α, IL-1β and IL-6 transcripts in colonic homogenates. Identical dosing for five days after established colitis produced similar recovery, outperforming 5-aminosalicylic acid and non-encapsulated PSB. [All animal experiments were performed following the Principles of Laboratory Animal Care and Guidelines of the Laboratory Animal Care Committee of Xi’an Jiaotong University (No: 2021-213).]

Mechanistic studies linked protection to reinforcement of the epithelial barrier. Immunofluorescence of tight-junction proteins ZO-1, occludin and claudin-1 displayed restored apical staining after PSB@MC; Alcian-blue counts of goblet cells rose to control levels, indicating mucus-layer rescue. Myeloperoxidase activity and malondialdehyde content dropped, and ROS-specific probes DCFH-DA and DHE showed the weakest luminal fluorescence in the treated group, corroborating antioxidant activity.

16S rDNA profiling disclosed that PSB@MC reversed DSS-induced expansion of Escherichia–Shigella and returned Muribaculaceae and Akkermansia to abundances comparable to healthy mice. Untargeted metabolomics identified 147 differential metabolites between DSS and PSB@MC groups; indole-3-carboxylic acid, gramine and bufotenine—known AHR ligands—were among the restored molecules. Consistently, qPCR and immunofluorescence displayed elevated AHR, Cyp1a1, Cyp1b1, IL-22 and IL-22RA expression in colonic tissue after treatment, aligning with the pathway’s reported barrier-strengthening effects.

Haematoxylin-eosin sections of heart, liver, spleen, lung and kidney, plus serum chemistry panels, remained unchanged following a 14-day PSB@MC course, and body-weight curves overlapped with vehicle controls, indicating favourable biocompatibility.

The authors conclude that prebiotic microcapsules offer a safe, inexpensive vehicle for ferrying pterostilbene to the inflamed colon, where the combined antioxidant, microbiota-modulating and AHR/IL-22-activating properties jointly restore mucosal homeostasis. They note that chronic-colitis models and functional-barrier assays are still needed, but the data support further development of PSB@MC as an orally administered adjunct for ulcerative-colitis management.

The paper “Prebiotic Microcapsule-encapsulated Pterostilbene Alleviates Ulcerative Colitis by Regulating the Intestinal Microenvironment and Activating AHR/IL-22 Pathway,” is authored by Huanyu Li, Ziwei Yang, Chuanyu Zhang, Xueyong Wei, Wenjing Wang, Ting Bai, Zhichao Deng, Bowen Gao, Manli Cui, Weixuan Jing, Mingzhen Zhang, Zhaoxiang Yu, Mingxin Zhang. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.04.026. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.