Américo Monique Ferrary, Freitas Andria Dos Santos, da Silva Tales Fernando, de Jesus Luís Cláudio Lima, Barroso Fernanda Alvarenga Lima, Campos Gabriela Munis, Santos Rhayane Cristina Viegas, Gomes Gabriel Camargos, Assis Rafael, Ferreira Ênio, Mancha-Agresti Pamela, Laguna Juliana Guimarães, Chatel Jean-Marc, Carvalho Rodrigo Dias de Oliveira, Azevedo Vasco
Department of Genetics, Ecology, and Evolution, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
INRAE, Institut Agro Rennes-Angers, STLO, Rennes, France.
Front Microbiol. 2023 Apr 17;14:1157544. doi: 10.3389/fmicb.2023.1157544. eCollection 2023.
Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including and results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers , and upregulation of in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant (pExu:) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.
黏膜炎是胃肠道黏膜的一种炎症，会削弱接受化疗患者的生活质量。在这种情况下，抗肿瘤药物，如5-氟尿嘧啶，会引发肠黏膜溃疡，通过激活核因子κB通路导致促炎细胞因子的分泌。使用益生菌菌株治疗该疾病的替代方法显示出有前景的结果，此后，可以进一步探索针对炎症部位的治疗方法。最近，研究报道蛋白质生长分化因子11（GDF11）在包括多种疾病中具有抗炎作用，并在不同实验模型中得到验证。因此，本研究评估了由乳酸乳球菌菌株NCDO2118和MG1363递送的GDF11在5-氟尿嘧啶诱导的小鼠肠道黏膜炎模型中的抗炎作用。我们的结果表明，用重组乳球菌菌株处理的小鼠肠道损伤的组织病理学评分有所改善，黏膜中杯状细胞变性减少。与阳性对照组相比，还观察到组织中中性粒细胞浸润显著减少。此外，我们观察到在用重组菌株处理的组中炎症标志物的免疫调节以及在mRNA表达水平上的上调，这有助于部分解释对黏膜的改善作用。因此，本研究结果表明，使用重组乳酸乳球菌（pExu:）可能为5-氟尿嘧啶诱导的肠道黏膜炎提供一种潜在的基因治疗方法。
