Alkushi Abdullah Glil, Elazab Sara T, Abdelfattah-Hassan Ahmed, Mahfouz Hala, Salem Gamal A, Sheraiba Nagwa I, Mohamed Eman A A, Attia Mai S, El-Shetry Eman S, Saleh Ayman A, ElSawy Naser A, Ibrahim Doaa
Department of Human Anatomy, Faculty of Medicine, Umm Al-Qura University, Al Abdeyah, Mecca 24382, Saudi Arabia.
Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Pharmaceutics. 2022 May 31;14(6):1183. doi: 10.3390/pharmaceutics14061183.
Gut modulation by multi-strain probiotics (MSPs) is considered an effective strategy for treating inflammatory bowel disease (IBD). The combination of nanomaterial-based MSPs can improve their viability and resistance and can allow their targeted release in the gastrointestinal tract to be achieved. Thus, our aim is to investigate the prospective role of MSP integration into nanomaterials (MSPNPs) and the underlying molecular mechanisms supporting their application as an alternative therapy for IBD using a colitis rat model. To induce the colitis model, rats received 5% DSS, and the efficacy of disease progression after oral administration of MSPNPs was assessed by evaluating the severity of clinical signs, inflammatory response, expressions of tight-junction-related genes and NLRP3 inflammasome and caspase-1 genes, microbial composition and histopathological examination of colonic tissues. The oral administration of MSPNPs successfully alleviated the colonic damage induced by DSS as proved by the reduced severity of clinical signs and fecal calprotectin levels. Compared with the untreated DSS-induced control group, the high activities of colonic NO and MPO and serum CRP levels were prominently reduced in rats treated with MSPNPs. Of note, colonic inflammation in the group treated with MSPNPs was ameliorated by downstreaming NLRP3 inflammasome, caspase-1, and expressions. After colitis onset, treatment with MSPNPs was more effective than that with free MSPs in restoring the expressions of tight-junction-related genes (upregulation of occludin, ZO-1, JAM, MUC and FABP-2) and beneficial gut microbiota. Interestingly, treatment with MSPNPs accelerated the healing of intestinal epithelium as detected in histopathological findings. In conclusion, the incorporation of MPSs into nanomaterials is recommended as a perspective strategy to overcome the challenges they face and augment their therapeutic role for treating of colitis.
多菌株益生菌（MSPs）对肠道的调节作用被认为是治疗炎症性肠病（IBD）的有效策略。基于纳米材料的多菌株益生菌组合可以提高其活力和抗性，并能实现其在胃肠道中的靶向释放。因此，我们的目的是使用结肠炎大鼠模型研究多菌株益生菌与纳米材料整合（MSPNPs）的潜在作用及其作为IBD替代疗法应用的潜在分子机制。为诱导结肠炎模型，给大鼠喂食5%的葡聚糖硫酸钠（DSS），通过评估临床症状的严重程度、炎症反应、紧密连接相关基因以及NLRP3炎性小体和半胱天冬酶 -1基因的表达、微生物组成和结肠组织的组织病理学检查，来评估口服MSPNPs后疾病进展的疗效。口服MSPNPs成功减轻了DSS诱导的结肠损伤，临床症状严重程度降低和粪便钙卫蛋白水平降低证明了这一点。与未治疗的DSS诱导对照组相比，MSPNPs处理的大鼠结肠中一氧化氮（NO）和髓过氧化物酶（MPO）的高活性以及血清C反应蛋白（CRP）水平显著降低。值得注意的是，MSPNPs处理组的结肠炎症通过下调NLRP3炎性小体、半胱天冬酶 -1的表达而得到改善。在结肠炎发作后，MSPNPs治疗在恢复紧密连接相关基因（闭合蛋白、紧密连接蛋白 -1、连接黏附分子、黏蛋白和脂肪酸结合蛋白 -2的上调）和有益肠道微生物群的表达方面比游离多菌株益生菌更有效。有趣的是，组织病理学检查发现，MSPNPs治疗加速了肠上皮的愈合。总之，建议将多菌株益生菌整合到纳米材料中，作为一种前瞻性策略来克服它们面临的挑战，并增强其治疗结肠炎的作用。
