Ghanbari Mahla, Motallebi Mitra, Karimi Merat, Aghadavood Esmat, Akhavan Taheri Maryam, Ahmadi Asouri Sahar, Amiri Siavash, Mirzaei Hamed, Shahaboddin Mohammad Esmaeil
Department of Clinical Biochemistry, Faculty of Medicine, Kashan University of Medical Sciences, Pezeshk Blvd, Qotbe Ravandi Blvd, P.O. Box: 8715973449, Kashan, Iran.
Infectious Disease Research Center, Kashan University of Medical Sciences, Kashan, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jul 22. doi: 10.1007/s00210-025-04452-w.
This study investigates the effects of encapsulated Bacillus subtilis (B. subtilis) on liver injury and fibrosis in a cholestatic rat model. Probiotics like B. subtilis have shown anti-inflammatory and antioxidant properties, but their efficacy is reduced by the harsh gastrointestinal tract (GIT) environment. Some studies have shown that encapsulation using a combination of alginate, Arabic gum, and chitosan can improve probiotic viability and promote controlled release in the intestine. In this study, male Wistar rats were randomly assigned to five groups: healthy control, cholestasis control, probiotic, free capsule, and encapsulated probiotic, to evaluate the protective effects of the encapsulated probiotic against cholestasis-induced damage. Encapsulated B. subtilis with the dosage of 3 × 10 CFU/day was administered 1 week before and 3 weeks after cholestasis induction. After treating rats with free or encapsulated B. subtilis, or with free microcapsules for 4 weeks, liver function tests, gene expression (pro- and anti-inflammatory cytokines), antioxidant status, and liver histology were analyzed. The results demonstrated that encapsulation enhanced the viability of the probiotic in the simulated gastrointestinal environment. Rats receiving encapsulated B. subtilis exhibited improved liver function, reduced pro-inflammatory cytokines (IL-6, TNF-α), and lower α-SMA gene expression (fibrosis marker), alongside increased anti-inflammatory IL-10. Additionally, antioxidant status was improved, and liver histology showed protective effects. These findings suggest that encapsulated B. subtilis can mitigate cholestasis-induced liver injury, enhance liver function, and prevent fibrosis progression.
本研究调查了包封枯草芽孢杆菌对胆汁淤积大鼠模型肝损伤和肝纤维化的影响。像枯草芽孢杆菌这样的益生菌已显示出抗炎和抗氧化特性，但其功效会因恶劣的胃肠道环境而降低。一些研究表明，使用藻酸盐、阿拉伯胶和壳聚糖的组合进行包封可以提高益生菌的活力，并促进其在肠道中的控释。在本研究中，将雄性Wistar大鼠随机分为五组：健康对照组、胆汁淤积对照组、益生菌组、游离胶囊组和包封益生菌组，以评估包封益生菌对胆汁淤积诱导损伤的保护作用。在胆汁淤积诱导前1周和诱导后3周，给予剂量为3×10 CFU/天的包封枯草芽孢杆菌。在用游离或包封的枯草芽孢杆菌或游离微胶囊处理大鼠4周后，分析肝功能测试、基因表达（促炎和抗炎细胞因子）、抗氧化状态和肝脏组织学。结果表明，包封提高了益生菌在模拟胃肠道环境中的活力。接受包封枯草芽孢杆菌的大鼠肝功能得到改善，促炎细胞因子（IL-6、TNF-α）减少，α-SMA基因表达（纤维化标志物）降低，同时抗炎性IL-10增加。此外，抗氧化状态得到改善，肝脏组织学显示出保护作用。这些发现表明，包封枯草芽孢杆菌可以减轻胆汁淤积诱导的肝损伤，增强肝功能，并防止纤维化进展。
