Barroso Fernanda Alvarenga Lima, de Jesus Luís Cláudio Lima, de Castro Camila Prosperi, Batista Viviane Lima, Ferreira Ênio, Fernandes Renata Salgado, de Barros André Luís Branco, Leclerq Sophie Yvette, Azevedo Vasco, Mancha-Agresti Pamela, Drumond Mariana Martins
Laboratório de Genética Celular e Molecular (LGCM), Departamento de-Genética, Ecologia e Evolução, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte 31270-901, Brazil.
Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil.
Microorganisms. 2021 Jan 5;9(1):107. doi: 10.3390/microorganisms9010107.
5-Fluorouracil (5-FU) is an antineoplastic drug that causes, as a side effect, intestinal mucositis, acute inflammation in the small bowel. The Heat Shock Protein (Hsp) are highly expressed in inflammatory conditions, developing an important role in immune modulation. Thus, they are potential candidates for the treatment of inflammatory diseases. In the mucositis mouse model, the present study aimed to evaluate the beneficial effect of oral administration of milk fermented by CIDCA 133 (pExu:), a recombinant strain. This approach showed increased levels of sIgA in the intestinal fluid, reducing inflammatory infiltrate and intestinal permeability. Additionally, the histological score was improved. Protection was associated with a reduction in the gene expression of pro-inflammatory cytokines such as Tnf, Il6, Il12, and Il1b, and an increase in Il10, Muc2, and claudin 1 (Cldn1) and 2 (Cldn2) gene expression in ileum tissue. These findings are corroborated with the increased number of goblet cells, the electronic microscopy images, and the reduction of intestinal permeability. The administration of milk fermented by this recombinant probiotic strain was also able to reverse the high levels of gene expression of Tlrs caused by the 5-FU. Thus, the rCIDCA 133:Hsp65 strain was revealed to be a promising preventive strategy for small bowel inflammation.
5-氟尿嘧啶（5-FU）是一种抗肿瘤药物，其副作用是导致肠道黏膜炎，即小肠急性炎症。热休克蛋白（Hsp）在炎症状态下高度表达，在免疫调节中发挥重要作用。因此，它们是治疗炎症性疾病的潜在候选物。在黏膜炎小鼠模型中，本研究旨在评估口服由重组菌株CIDCA 133（pExu:）发酵的牛奶的有益效果。这种方法显示肠液中分泌型免疫球蛋白A（sIgA）水平升高，炎症浸润和肠道通透性降低。此外，组织学评分得到改善。保护作用与促炎细胞因子如肿瘤坏死因子（Tnf）、白细胞介素6（Il6）、白细胞介素12（Il12）和白细胞介素1β（Il1b）的基因表达降低有关，同时回肠组织中白细胞介素10（Il10）、黏蛋白2（Muc2）以及紧密连接蛋白1（Cldn1）和紧密连接蛋白2（Cldn2）的基因表达增加。这些发现与杯状细胞数量增加、电子显微镜图像以及肠道通透性降低相一致。给予这种重组益生菌菌株发酵的牛奶还能够逆转由5-FU引起的Toll样受体（Tlrs）基因表达的高水平。因此，rCIDCA 133:Hsp65菌株被证明是一种有前景的预防小肠炎症的策略。
