Engineered probiotics with sustained release of interleukin-2 for the treatment of inflammatory bowel disease after oral delivery

Maoyi Li; Nanhui Liu; Jiafei Zhu; Yumin Wu; Le Niu; Yi Liu; Linfu Chen; Boxiong Bai; Yu Miao; Yang Yang; Qian Chen

doi:10.1016/j.biomaterials.2024.122584

Engineered probiotics with sustained release of interleukin-2 for the treatment of inflammatory bowel disease after oral delivery

Biomaterials. 2024 May 8:309:122584. doi: 10.1016/j.biomaterials.2024.122584. Online ahead of print.

Authors

Maoyi Li¹, Nanhui Liu¹, Jiafei Zhu¹, Yumin Wu¹, Le Niu¹, Yi Liu², Linfu Chen¹, Boxiong Bai¹, Yu Miao¹, Yang Yang², Qian Chen³

Affiliations

¹ Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, China.
² Department of Thoracic Surgery Shanghai Pulmonary Hospital School of Medicine Tong ji University, Shanghai, 200433, China.
³ Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, 215123, China. Electronic address: chenqian@suda.edu.cn.

PMID: 38735180
DOI: 10.1016/j.biomaterials.2024.122584

Abstract

Inflammatory bowel disease (IBD) is a kind of auto-immune disease characterized by disrupted intestinal barrier and mucosal epithelium, imbalanced gut microbiome and deregulated immune responses. Therefore, the restoration of immune equilibrium and gut microbiota could potentially serve as a hopeful approach for treating IBD. Herein, the oral probiotic Escherichia coli Nissle 1917 (ECN) was genetically engineered to express secretable interleukin-2 (IL-2), a kind of immunomodulatory agent, for the treatment of IBD. In our design, probiotic itself has the ability to regulate the gut microenvironment and IL-2 at low dose could selectively promote the generation of regulatory T cells to elicit tolerogenic immune responses. To improve the bioavailability of ECN expressing IL-2 (ECN-IL2) in the gastrointestinal tract, enteric coating Eudragit L100-55 was used to coat ECN-IL2, achieving significantly enhanced accumulation of engineered probiotics in the intestine. More importantly, L100-55 coated ECN-IL2 could effectively activated Treg cells to regulate innate immune responses and gut microbiota, thereby relieve inflammation and repair the colon epithelial barrier in dextran sodium sulfate (DSS) induced IBD. Therefore, genetically and chemically modified probiotics with excellent biocompatibility and efficiency in regulating intestinal microflora and intestinal inflammation show great potential for IBD treatment in the future.

Keywords: Chemical modification; Engineered probiotics; Inflammatory bowel disease; Interleukin-2; Oral delivery.