Meng Yueyue, Wang Jing, Wang Zhiyu, Zhang Guofang, Liu Libo, Huo Guicheng, Li Chun
Key Laboratory of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin, China.
Front Microbiol. 2019 Apr 12;10:731. doi: 10.3389/fmicb.2019.00731. eCollection 2019.
Cyclophosphamide (CTX), a clinically important antineoplastic drug, also leads to some side effects such as nausea, vomiting and diarrhea in the consumer. In this study, () KLDS1.0318 preserved in our laboratory was orally administered to CTX-treated mice to explore its potential effects to attenuate the toxic effects of CTX-induced by modulating intestinal immune response, promoting intestinal integrity and improving metabolic profile. BALB/c mice were randomly divided into six groups including normal control group (NC; non-CTX with sterile saline), model control group (MC; CTX-treated with sterile saline), CTX-treated with KLDS1.0318 (10 mL/kg) groups with three different doses (KLDS1.0318-L, 5 × 10 CFU/mL; KLDS1.0318-M, 5 × 10 CFU/mL; KLDS1.0318-H, 5 × 10 CFU/mL), and CTX-treated with levamisole hydrochloride (40 mg/kg) as a positive control (PC) group. After receiving the bacterium for 20 days, samples of small intestine and colonic contents were collected for different analyses. The results revealed that the levels of cytokines secreted by Th1 cells (IL-2, IFN-γ, and TNF-α) and Th2 cells (IL-4, IL-6, and IL-10) in probiotic treatment groups were significantly higher than those in the MC group. Histopathological results showed that KLDS1.0318 favorably recovered CTX-induced abnormal intestinal morphology by improving the villus height and crypt depth as well as quantity of goblet cells and mucins production. Compared to CTX alone-treated group, the production of short-chain fatty acids (SCFAs) were significantly increased and the levels of pH and ammonia were decreased significantly with high dose KLDS1.0318 supplementation. Compared with mice in CTX alone-treated group, mice in three groups of KLDS1.0318 had increased and and decreased and in their cecal content. The present findings suggested that KLDS1.0318 could be of significant advantage to mitigate the harmful effects of CTX and improve the intestinal health in mice.
环磷酰胺（CTX）是一种临床上重要的抗肿瘤药物，也会给使用者带来一些副作用，如恶心、呕吐和腹泻。在本研究中，将保存在我们实验室的（）KLDS1.0318口服给予CTX处理的小鼠，以探索其通过调节肠道免疫反应、促进肠道完整性和改善代谢状况来减轻CTX诱导的毒性作用的潜在效果。BALB/c小鼠被随机分为六组，包括正常对照组（NC；用无菌生理盐水而非CTX处理）、模型对照组（MC；用无菌生理盐水处理CTX）、用三种不同剂量（KLDS1.0318-L，5×10 CFU/mL；KLDS1.0318-M，5×10 CFU/mL；KLDS1.0318-H，5×10 CFU/mL）的KLDS1.0318处理CTX的组，以及用盐酸左旋咪唑（40 mg/kg）处理CTX作为阳性对照组（PC）。接受细菌处理20天后，收集小肠和结肠内容物样本进行不同分析。结果显示，益生菌处理组中Th1细胞（IL-2、IFN-γ和TNF-α）和Th2细胞（IL-4、IL-6和IL-10）分泌的细胞因子水平显著高于MC组。组织病理学结果表明，KLDS1.0318通过改善绒毛高度、隐窝深度以及杯状细胞数量和粘蛋白产生，有利地恢复了CTX诱导的异常肠道形态。与单独使用CTX处理组相比，补充高剂量KLDS1.0318后，短链脂肪酸（SCFAs）的产生显著增加，pH值和氨水平显著降低。与单独使用CTX处理组的小鼠相比，KLDS1.0318三组小鼠盲肠内容物中的（此处原文似乎不完整）增加，（此处原文似乎不完整）减少。目前的研究结果表明，KLDS1.0318在减轻CTX的有害影响和改善小鼠肠道健康方面可能具有显著优势。
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