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  2. Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment

Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment

  • J Control Release. 2024 Oct:374:140-153. doi: 10.1016/j.jconrel.2024.07.071.
Jiali Yang 1 Shengchan Ge 2 Shaochong Tan 2 Hua Liu 2 Mingzhu Yang 2 Wei Liu 2 Kaixiang Zhang 2 Zhenzhong Zhang 2 Junjie Liu 2 Jinjin Shi 3 Zhi-Hao Wang 4 Jitian Li 5
Affiliations

Affiliations

  • 1 Institute of Brain Science and Disease, School of Basic Medicine, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao 266021, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
  • 2 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China.
  • 3 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: shijinyxy@zzu.edu.cn.
  • 4 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China. Electronic address: wangzhihao@zzu.edu.cn.
  • 5 Henan Luoyang Orthopedic Hospital (Henan Provincial Orthopedic Hospital), 100 Yongping Road, Zhengzhou 450000, China. Electronic address: jitianlee@hotmail.com.
Abstract

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H2S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H2S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially Other mucus-depletion-related diseases.

Keywords

Depleted mucus; Hydrogen sulfide; Inflammatory bowel disease; Montmorillonite; Probiotics colonization.

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