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Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment
Journal of Controlled Release ( IF 10.5 ) Pub Date : 2024-08-14 , 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 2 , Zhi-Hao Wang 2 , Jitian Li 3
Affiliation  

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.

中文翻译:


改良蒙脱土武装益生菌,具有增强的粘液耗尽肠道定植和 H2S 清除能力,用于结肠炎治疗



炎症性肠病(IBD)通常与肠道菌群失调和过度炎症微环境有关。益生菌治疗与炎症管理相结合是缓解 IBD 的一种有前景的方法,但其疗效因益生菌在粘液耗尽的炎症性肠段中的定植较差而受到阻碍。在这里,我们提出了改良蒙脱土武装益生菌大肠杆菌 Nissle 1917 (MMT-Fe@EcN),其具有增强的肠道定植和硫化氢 (H2S) 清除能力,可协同缓解 IBD。蒙脱石层可以保护EcN在口服给药过程中免受环境侵害,并由于其强大的粘附能力和电负性而改善EcN在粘液耗尽的肠段中的现场定植,与EcN相比,定植效率提高了22.6倍。同时,MMT-Fe@EcN 可以通过清除 H2S 来控制炎症,从而增强益生菌的活力和定殖,从而恢复肠道微生物群。因此,MMT-Fe@EcN 在葡聚糖硫酸钠诱导的小鼠结肠炎模型中表现出非凡的治疗效果,包括减轻肠道炎症、恢复受损的肠道屏障功能和肠道微生物群。这些发现为 IBD 的临床治疗和其他潜在的粘液消耗相关疾病提供了一种有前景的策略。
更新日期:2024-08-14
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