Prebiotic microcapsules deliver pterostilbene to the colon to alleviate ulcerative colitis

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.