Rather Irfan A, Bajpai Vivek K, Ching Lew L, Majumder Rajib, Nam Gyeong-Jun, Indugu Nagaraju, Singh Prashant, Kumar Sanjay, Hajrah Nahid H, Sabir Jamal S M, Kamli Majid Rasool, Park Yong-Ha
Department of Applied Microbiology and Biotechnology, School of Biotechnology, Yeungnam University, Gyeongsan, Gyeongbuk 712-749, Republic of Korea.
Centre of Excellence in Bionanoscience Research, King Abdulaziz University (KAU), Jeddah 21589, Saudi Arabia.
Saudi J Biol Sci. 2020 Jan;27(1):261-270. doi: 10.1016/j.sjbs.2019.09.004. Epub 2019 Sep 4.
This study underpins the therapeutic potential of SEL001, a bioactive product isolated from probio65, in terms of its anti-inflammatory properties and its effect on gut-microbiota in a TNBS-induced ulcerative colitis mouse model. Ulcerative colitis was developed in mice by intra rectal administration of trinitrobenzene sulfonic acid. Bioactive product SEL001 (50 mg/kg b.w.) was administered orally. Myeloperoxidase activity was measured using 3,3', 5,5'-tetramethylbenzidine. The entire colon was sampled for post-mortem clinical assessment. Colonic injury was assessed through histological and histomorphometric examinations. The 454 pyrosequencing and QIIME pipeline were used for gut microbiota analysis and statistical analysis were conducted using R. mRNA extraction from colon tissue and RT-PCR approaches were employed to determine the changes in the level of specific biomarker genes associated with UC. The results depict that SEL001 significantly lowered pro-inflammatory cytokines, including CD4, TNF-α, and interleukin-6. Examination of clinical and histopathological traits revealed that SEL001 was effective and potent in reducing the inflammatory signatures of UC to a similar extent as did by the standard drug mesalamine (5-ASA). Pyro-sequencing 16S data revealed that the reduction in the major member of phylum Firmicutes, which has been previously associated with a higher risk of UC. The SEL001, an anti-inflammatory bioactive product originated from a probiotic strain probio65 could be an alternative therapeutic agent for treatment of UC.
本研究证实了从probio65中分离出的生物活性产物SEL001在三硝基苯磺酸(TNBS)诱导的溃疡性结肠炎小鼠模型中的抗炎特性及其对肠道微生物群的影响方面的治疗潜力。通过直肠内给予三硝基苯磺酸在小鼠中诱发溃疡性结肠炎。口服给予生物活性产物SEL001(50mg/kg体重)。使用3,3',5,5'-四甲基联苯胺测量髓过氧化物酶活性。对整个结肠进行采样以进行死后临床评估。通过组织学和组织形态计量学检查评估结肠损伤。使用454焦磷酸测序和QIIME管道进行肠道微生物群分析,并使用R进行统计分析。从结肠组织中提取mRNA并采用RT-PCR方法来确定与溃疡性结肠炎相关的特定生物标志物基因水平的变化。结果表明,SEL001显著降低了促炎细胞因子,包括CD4、肿瘤坏死因子-α和白细胞介素-6。临床和组织病理学特征检查显示,SEL001在减轻溃疡性结肠炎的炎症特征方面有效且有力,其程度与标准药物美沙拉嗪(5-ASA)相似。焦磷酸测序16S数据显示,厚壁菌门的主要成员减少,而厚壁菌门此前被认为与溃疡性结肠炎的较高风险相关。源自益生菌菌株probio65的抗炎生物活性产物SEL001可能是治疗溃疡性结肠炎的替代治疗剂。