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长双歧杆菌亚种 longum 5 减轻伊立替康诱导的小鼠黏膜炎的肠道损伤。

Bifidobacterium longum subsp. longum 5 attenuates intestinal injury against irinotecan-induced mucositis in mice.

机构信息

Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.

出版信息

Life Sci. 2022 Jan 15;289:120243. doi: 10.1016/j.lfs.2021.120243. Epub 2021 Dec 16.

Abstract

Intestinal mucositis (IM) is a critical side-effect associated with antineoplastic therapy. Treatment available is only palliative and often not effective. However, alternative therapeutic strategies, such as probiotics, have attracted significant attention due to their immune-modulatory action in several diseases. Thus, the present study aims to elucidate the therapeutic potential of the probiotic strain Bifidobacterium longum 5 in a murine model of mucositis induced by irinotecan. Due to the scarcity of studies on dose-response and viability (probiotic vs paraprobiotic), we first evaluated which dose and cell viability would be most effective in treating mucositis. In this study, the oral pretreatment with viable B. longum 5 at a concentration of 1 × 10 CFU/mL reduced the daily disease activity index (p < 0.01), protected the intestinal architecture, preserved the length of the intestine (p < 0.05), and reduced intestinal permeability (p < 0.01), inflammation, and oxidative damage (p < 0.01) induced by irinotecan. Also, treatment with B. longum 5 increased the production of secretory immunoglobulin A (p < 0.05) in the intestinal fluid of mice with mucositis. Furthermore, B. longum 5 reversed the mucositis-induced increase in Enterobacteriaceae bacterial group in the gut (p < 0.01). In conclusion, these results showed that oral administration of B. longum 5 protects mice against intestinal damage caused by irinotecan, suggesting its use as a potential probiotic in therapy during mucositis.

摘要

肠黏膜炎(IM)是一种与抗肿瘤治疗相关的严重副作用。现有的治疗方法只是对症治疗,而且往往效果不佳。然而,由于益生菌在多种疾病中具有免疫调节作用,因此替代治疗策略,如益生菌,引起了人们的极大关注。因此,本研究旨在探讨益生菌长双歧杆菌 5 在伊立替康诱导的黏膜炎小鼠模型中的治疗潜力。由于剂量-反应和存活(益生菌与副益生菌)的研究很少,我们首先评估了哪种剂量和细胞活力对治疗黏膜炎最有效。在这项研究中,口服预处理活的长双歧杆菌 5 的浓度为 1×10 CFU/mL 可降低每日疾病活动指数(p<0.01),保护肠结构,保持肠的长度(p<0.05),降低肠通透性(p<0.01)、炎症和氧化损伤(p<0.01)由伊立替康引起的。此外,长双歧杆菌 5 治疗增加了黏膜炎小鼠肠道液中分泌型免疫球蛋白 A 的产生(p<0.05)。此外,长双歧杆菌 5 逆转了黏膜炎诱导的肠道中肠杆菌科细菌群的增加(p<0.01)。总之,这些结果表明,口服长双歧杆菌 5 可保护小鼠免受伊立替康引起的肠道损伤,提示其在黏膜炎治疗中可用作潜在的益生菌。

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