Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Departamento de Bioquímica E Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
Probiotics Antimicrob Proteins. 2024 Feb;16(1):275-292. doi: 10.1007/s12602-023-10040-2. Epub 2023 Jan 18.
Mucositis is a high-incidence side effect in cancer patients undergoing chemotherapy. Next-generation probiotics are emerging as new therapeutic tools for managing various disorders. Studies have demonstrated the potential of Akkermansia muciniphila to increase the efficiency of anticancer treatment and to mitigate mucositis. Due to the beneficial effect of A. muciniphila on the host, we evaluated the dose-response, the microorganism viability, and the treatment protocol of A. muciniphila BAA-835 in a murine model of chemotherapy-induced mucositis. Female Balb/c mice were divided into groups that received either sterile 0.9% saline or A. muciniphila by gavage. Mucositis was induced using a single intraperitoneal injection of 5-fluorouracil. The animals were euthanized three days after the induction of mucositis, and tissue and blood were collected for analysis. Prevention of weight loss and small intestine shortening and reduction of neutrophil and eosinophil influx were observed when animals were pretreated with viable A. muciniphila at 10 colony-forming units per mL (CFU/mL). The A. muciniphila improved mucosal damage by preserving tissue architecture and increasing villus height and goblet cell number. It also improved the integrity of the epithelial barrier, decreasing intestinal permeability and bacterial translocation. In addition, the treatment prevented the expansion of Enterobacteriaceae. The immunological parameters were also improved by decreasing the expression of pro-inflammatory cytokines (IL6, IL1β, and TNF) and increasing IL10. In conclusion, pretreatment with 10 CFU/mL of viable A. muciniphila effectively controlled inflammation, protected the intestinal mucosa and the epithelial barrier, and prevented Enterobacteriaceae expansion in treated mice.
黏膜炎是癌症患者化疗时高发的副作用。新一代益生菌作为管理各种疾病的新治疗工具正在出现。研究表明，阿克曼氏菌（Akkermansia muciniphila）有增加抗癌治疗效率和减轻黏膜炎的潜力。由于 A. muciniphila 对宿主有有益的影响，我们评估了化疗诱导黏膜炎的小鼠模型中 A. muciniphila BAA-835 的剂量反应、微生物活力和治疗方案。雌性 Balb/c 小鼠分为接受无菌 0.9%生理盐水或 A. muciniphila 灌胃的组。通过单次腹腔注射氟尿嘧啶诱导黏膜炎。诱导黏膜炎 3 天后，处死动物并收集组织和血液进行分析。当用 10 个菌落形成单位/毫升（CFU/mL）的活菌预处理动物时，观察到预防体重减轻和小肠缩短以及减少中性粒细胞和嗜酸性粒细胞流入的作用。A. muciniphila 改善了黏膜损伤，保留了组织结构，增加了绒毛高度和杯状细胞数量。它还改善了上皮屏障的完整性，减少了肠道通透性和细菌易位。此外，该治疗还阻止了肠杆菌科的扩张。通过降低促炎细胞因子（IL6、IL1β 和 TNF）的表达和增加 IL10，治疗还改善了免疫参数。总之，用 10 CFU/mL 的活菌预处理 A. muciniphila 有效控制了炎症，保护了肠黏膜和上皮屏障，并防止了治疗小鼠中肠杆菌科的扩张。
