Probiotic-based therapies have been shown to be beneficial for chemotherapy-induced mucositis. Previous research has demonstrated that a probiotic mixture (Bifidobacterium brevis, Lactobacillus acidophilus, Lactobacillus casei, and Streptococcus thermophilus) can ameliorate chemotherapy-induced mucositis and dysbiosis in rats, but the underlying mechanism has not been completely elucidated. We aimed to determine the inhibitory effects of the probiotic mixture on cisplatin-induced mucositis and pica and the underlying mechanism, focusing on the levels of 5-hydroxytryptamine (5-HT, serotonin) regulated by the gut microbiota. A rat model of mucositis and pica was established by daily intraperitoneal injection of cisplatin (6 mg/kg) for 3 days. In the probiotic+cisplatin group, predaily intragastric injection of the probiotic mixture ( BW) was administrated for 1 week before cisplatin injection. This was then followed by further daily probiotic injections for 6 days. Histopathology, pro-/anti-inflammatory cytokines, oxidative status, and 5-HT levels were assessed on days 3 and 6. The structure of the gut microbiota was analyzed by 16S rRNA gene sequencing and quantitative PCR. Additionally, 5-HT levels in enterochromaffin (EC) cells (RIN-14B cell line) treated with cisplatin and/or various probiotic bacteria were also determined. The probiotic mixture significantly attenuated kaolin consumption, inflammation, oxidative stress, and the increase in 5-HT concentrations in rats with cisplatin-induced intestinal mucositis and pica. Cisplatin markedly increased the relative abundances of Enterobacteriaceae_other, Blautia, Clostridiaceae_other, and members of Clostridium clusters IV and XIVa. These levels were significantly restored by the probiotic mixture. Importantly, most of the genera increased by cisplatin were significantly positively correlated with colonic 5-HT. Furthermore, in vitro, the probiotic mixture had direct inhibitory effects on the 5-HT secretion by EC cells. The probiotic mixture protects against cisplatin-induced intestine injury, exhibiting both anti-inflammatory and antiemetic properties. These results were closely related to the reestablishment of intestinal microbiota ecology and normalization of the dysbiosis-driven 5-HT overproduction.

中文翻译：

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益生菌混合物的给药通过调节大鼠中的 5-HT 来改善顺铂诱导的粘膜炎和异食癖

基于益生菌的疗法已被证明对化疗引起的粘膜炎有益。先前的研究表明，益生菌混合物（短双歧杆菌、嗜酸乳杆菌、干酪乳杆菌和嗜热链球菌）) 可以改善化疗引起的大鼠粘膜炎和生态失调，但其潜在机制尚未完全阐明。我们旨在确定益生菌混合物对顺铂诱导的粘膜炎和异食癖的抑制作用及其潜在机制，重点是肠道微生物群调节的 5-羟色胺（5-HT，5-羟色胺）水平。每天腹腔注射顺铂（6 mg/kg）3天，建立大鼠黏膜炎和异食癖模型。在益生菌+顺铂组中，每天预先灌胃益生菌混合物（BW) 在顺铂注射前给药 1 周。然后每天进一步注射益生菌，持续 6 天。在第 3 天和第 6 天评估组织病理学、促炎/抗炎细胞因子、氧化状态和 5-HT 水平。通过 16S rRNA 基因测序和定量 PCR 分析肠道微生物群的结构。此外，还测定了用顺铂和/或各种益生菌处理的肠嗜铬 (EC) 细胞（RIN-14B 细胞系）中的 5-HT 水平。益生菌混合物显着减轻了顺铂诱导的肠粘膜炎和异食癖大鼠的高岭土消耗、炎症、氧化应激和 5-HT 浓度的增加。顺铂显着增加肠杆菌科细菌的相对丰度，Blautia、Clostridiaceae_other和梭菌簇 IV 和 XIVa 的成员。益生菌混合物显着恢复了这些水平。重要的是，顺铂增加的大多数属与结肠 5-HT 显着正相关。此外，在体外，益生菌混合物对 EC 细胞的 5-HT 分泌具有直接抑制作用。益生菌混合物可防止顺铂引起的肠道损伤，同时具有抗炎和止吐特性。这些结果与肠道微生物群生态的重建和生态失调驱动的 5-HT 过度生产的正常化密切相关。