Hierarchical arming of probiotics for improved viability to synergistically alleviate ulcerative colitis.

Oral intake of probiotics has potential benefits for alleviating ulcerative colitis (UC); however, the challenging environments (e.g., gastric acid and bile salts) in the gastrointestinal tract hinder their effectiveness. Additionally, the instability of probiotics during processing and storage hinders their practical application. To address this issue, protective strategies, including single-cell coating and microencapsulation, have been recently proposed. However, the protective efficacy requires further improvement to maximize the oral therapeutic benefits of probiotics. Herein, we integrated single-cell coating of β-glucan (GN) with soy protein isolate (SPI)-based microencapsulation to achieve hierarchical arming of the probiotic Lactobacillus reuteri (Lr). After oral administration, the hierarchical arming (Lr@GN@SPI) comprising GN coating and a three-dimensional SPI network effectively shielded the inner Lr from direct contact with the gastrointestinal environment during transit, significantly enhancing their viability, which outperformed those achieved by either single-cell coating or microencapsulation. In the intestine, SPI was progressively degraded by trypsin, whereas the gut microbiota metabolized GN into short-chain fatty acids (SCFAs), collectively resulting in the controlled release of Lr. This triggered a synergistic effect between living Lr and SCFAs in the treatment of UC. Consequently, oral administration of Lr@GN@SPI effectively alleviated UC in both therapeutic and preventive mouse models by reversing intestinal mucosal integrity, modulating the inflammatory response, and rebalancing the gut microbiota. In conclusion, our strategy, which utilizes food-grade substrates, offers valuable insight into the protection of probiotics and provides a promising approach for managing gut health-related diseases.