Intestinal mucositis is a commonly encountered toxic side effect in patients undergoing 5-fluorouracil (5-FU)-based chemotherapy. Numerous studies have shown that probiotics enable improving chemotherapy-induced intestinal mucositis, but the beneficial effects of probiotics differ depending on the strain. Therefore, in the present studies we suggest that S. thermophilus ST4 separated from raw milk may assess mucoprotective activity in 5-FU-induced intestinal mucositis. In our causal-comparative study design, fifteen mice were randomized assigned into three groups (n = 5/each group): control group, 5-FU group and 5-FU+S. thermophilus ST4 group. The control group was orally administrated saline only, and the 5-FU group was followed by intraperitoneal injection of 5-FU for 3 days after 10-day saline administration, and the 5-FU+S. thermophilus ST4 group was intragastrically subjected for S. thermophilus ST4 once per day during the whole experiment, starting from the first day of the experiment, followed by 5-FU intraperitoneal injection for 3 days after 10-day S. thermophilus ST4 pretreatment. Diarrhea score, pro-inflammatory cytokines serum levels, intestinal histopathology and short chain fatty acid were assessed. Here, we demonstrated the beneficial effects of S. thermophilus ST4 derived from raw milk against 5-FU-induced intestinal mucositis, including body weight reduction, appetite loss and diarrhea. Intrinsically, S. thermophilus ST4 effectively maintained epithelium structure in small intestines and colons as well as reduced the intestinal inflammation. Besides, S. thermophilus ST4 significantly increased the expression of acetic acid, reinforcing the muco-protective effects. In conclusion, our results demonstrate that S. thermophilus ST4 supplementation ameliorates 5-FU-induced intestinal mucositis. This suggests probiotic may serve as an alternative therapeutic strategy for the prevention or management of 5-FU-induced mucositis in the future.

中文翻译：

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嗜热链球菌 ST4 在小鼠模型中改善 5-氟尿嘧啶诱导的肠粘膜炎。

肠粘膜炎是接受基于 5-氟尿嘧啶 (5-FU) 化疗的患者常见的毒副作用。大量研究表明，益生菌能够改善化疗引起的肠道粘膜炎，但益生菌的有益作用因菌株而异。因此，在目前的研究中，我们建议从生奶中分离出的嗜热链球菌 ST4 可以评估 5-FU 诱导的肠粘膜炎的粘膜保护活性。在我们的因果比较研究设计中，将 15 只小鼠随机分为三组（n = 5/每组）：对照组、5-FU 组和 5-FU+S。嗜热 ST4 组。对照组仅口服生理盐水，5-FU组10天生理盐水后腹腔注射5-FU 3天，5-FU+S。嗜热链球菌ST4组在整个实验过程中每天一次灌胃嗜热链球菌ST4，从实验的第一天开始，然后在10天的嗜热链球菌ST4预处理后5-FU腹腔注射3天。评估了腹泻评分、促炎细胞因子血清水平、肠道组织病理学和短链脂肪酸。在这里，我们展示了源自生奶的嗜热链球菌 ST4 对 5-FU 诱导的肠道粘膜炎的有益作用，包括体重减轻、食欲减退和腹泻。从本质上讲，嗜热链球菌 ST4 有效地维持了小肠和结肠的上皮结构，并减少了肠道炎症。此外，嗜热链球菌 ST4 显着增加了乙酸的表达，加强粘液保护作用。总之，我们的结果表明，嗜热链球菌 ST4 补充剂可改善 5-FU 诱导的肠粘膜炎。这表明益生菌可以作为未来预防或管理 5-FU 诱导的粘膜炎的替代治疗策略。