Reportedly, antibiotics, which are frequently prescribed in children, have long-term effects owing to gut microbiota dysregulation. Tosufloxacin tosilate hydrate (TFLX) is the first orally administered new quinolone with high efficacy and broad-spectrum action approved as an antibacterial agent for pediatric use in Japan. However, studies on the effects of its early-stage administration are limited. Therefore, we aimed to analyze the later effects of its developmental administration by monitoring growth rate, neurobehavior, and gut microbiota in mice. The TFLX was administered via drinking water at a dose of up to 300 mg/kg for two consecutive weeks during the developmental period (4-6 weeks of age) or adulthood (8-10 weeks of age). Thereafter, the body weights of the mice were measured weekly to monitor growth rate. Behavioral tests were also conducted on 11-12-week-old mice to examine the neurobehavioral effects of the treatment. Further, to examine the effects of the treatment on microbiota, fecal samples were collected from the rectum of mice dissected at 12 weeks of age, and 16s rRNA analysis was conducted. Our results showed increased body weights after TFLX administration, without any long-term effects. Behavioral analysis suggested alterations in anxiety-like behaviors and memory recall dysregulation, and gut microbiota analysis revealed significant differences in bacterial composition. These findings indicated that TFLX administration during the developmental period affects mice growth rate, neurobehavior, and gut microbiota structure. This is the first study to report that TFLX is potentially associated with the risk of long effects.

中文翻译：

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生命早期给予托舒沙星甲苯磺酸盐水合物对雄性小鼠成年期生长速度、神经行为和肠道微生物群的影响。

据报道，由于肠道菌群失调，经常给儿童开处方的抗生素会产生长期影响。Tosufloxacin tosilate hydrate (TFLX) 是第一个口服给药的新型喹诺酮类药物，具有高效和广谱作用，在日本被批准为儿科抗菌药物。然而，对其早期给药效果的研究是有限的。因此，我们旨在通过监测小鼠的生长速度、神经行为和肠道微生物群来分析其发育管理的后期影响。TFLX 在发育期（4-6 周龄）或成年期（8-10 周龄）期间通过饮用水以高达 300 mg/kg 的剂量连续两周给药。此后，每周测量小鼠的体重以监测生长速率。还对 11-12 周大的小鼠进行了行为测试，以检查治疗的神经行为影响。此外，为了检查治疗对微生物群的影响，从 12 周大时解剖的小鼠直肠收集粪便样本，并进行 16s rRNA 分析。我们的结果显示 TFLX 给药后体重增加，没有任何长期影响。行为分析表明焦虑样行为和记忆回忆失调发生了改变，肠道微生物群分析揭示了细菌组成的显着差异。这些发现表明，在发育期间施用 TFLX 会影响小鼠的生长速度、神经行为和肠道微生物群结构。这是第一项报告 TFLX 可能与长期影响风险相关的研究。