Yeung Chun-Yan, Chiau Jen-Shiu Chiang, Cheng Mei-Lien, Chan Wai-Tao, Chang Szu-Wen, Jiang Chuen-Bin, Lee Hung-Chang
Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children's Hospital, Taipei, Taiwan.
Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
Gastroenterol Res Pract. 2021 Jan 25;2021:3068393. doi: 10.1155/2021/3068393. eCollection 2021.
Intestinal mucositis remains one of the most deleterious side effects in cancer patients undergoing chemotherapy. We hypothesize that the probiotics could preserve gut ecology, ameliorate inflammation, and protect epithelia via immune modulations of enterocytes and intestinal stem cells. Our aim is to characterize these changes and the safety of probiotics via a 5-fluorouracil- (5-FU-) induced intestinal mucositis mouse model.
5-FU-injected BALB/c mice were either orally administrated with saline or probiotic suspension of variety (Lcr35). Diarrhea scores, serum proinflammatory cytokines, and T-cell subtypes were assessed. Immunostaining analyses for the proliferation of intestinal stem cells CD44 and Ki67 were processed. Samples of blood and internal organs were investigated for bacterial translocation.
Diarrhea was attenuated after oral Lcr35 administration. Serum proinflammatory cytokines were significantly increased in the 5-FU group and were reversed by Lcr35. A tremendous rise of the CD3/CD8 count and a significant decrease of CD3CD4/CD3CD8 ratios were found in the 5-FU group and were both reversed by Lcr35. 5-FU significantly stimulated the expression of CD44 stem cells, and the expression was restored by Lcr35. 5-FU could increase the number of Ki67 proliferative cells. No bacterial translocation was found in this study.
Our results showed that 5-FU caused intestinal inflammation mainly via Th1 and Th17 responses. 5-FU could stimulate stem cells and proliferation cells in a mouse model. We demonstrate chemotherapy could decrease immune competence. Probiotics were shown to modulate the immune response. This is the first study to analyze the immune modulation effects and safety of strain on enterocytes and intestinal stem cells in a mouse model.
肠道黏膜炎仍然是接受化疗的癌症患者中最有害的副作用之一。我们假设益生菌可以通过对肠上皮细胞和肠道干细胞的免疫调节来维持肠道生态、减轻炎症并保护上皮细胞。我们的目的是通过5-氟尿嘧啶（5-FU）诱导的肠道黏膜炎小鼠模型来表征这些变化以及益生菌的安全性。
给注射了5-FU的BALB/c小鼠口服生理盐水或不同种类的益生菌悬液（Lcr35）。评估腹泻评分、血清促炎细胞因子和T细胞亚型。对肠道干细胞CD44和Ki67的增殖进行免疫染色分析。对血液和内脏样本进行细菌移位研究。
口服Lcr35后腹泻减轻。5-FU组血清促炎细胞因子显著增加，而Lcr35使其逆转。5-FU组CD3/CD8计数大幅上升，CD3CD4/CD3CD8比值显著下降，两者均被Lcr35逆转。5-FU显著刺激CD44干细胞的表达，而Lcr35使其表达恢复。5-FU可增加Ki67增殖细胞的数量。本研究中未发现细菌移位。
我们的结果表明，5-FU主要通过Th1和Th17反应引起肠道炎症。在小鼠模型中，5-FU可刺激干细胞和增殖细胞。我们证明化疗会降低免疫能力。益生菌被证明可调节免疫反应。这是第一项在小鼠模型中分析某菌株对肠上皮细胞和肠道干细胞的免疫调节作用及安全性的研究。
