Current antidepressants do not confer a clear advantage in children and adolescents with major depressive disorder (MDD). Accumulating evidence highlights the potential antidepressant-like effects of inosine on adult MDD, and gut microbiomes are significantly associated with MDD via the microbiota-gut-brain axis. However, few studies have investigated possible associations between inosine and gut microbiota in adolescents with MDD. The current study investigated the potential antidepressant effects of inosine in adolescent male C57BL/6 mice. After 4 weeks of chronic unpredictable mild stress (CUMS) stimulation, the mice were assessed by body weight, the sucrose preference test (SPT), open field test, and the elevated plus maze (EPM). The microbiota compositions of feces were determined by 16S rRNA gene sequencing. Inosine significantly improved CUMS-induced depressive and anxiety-like behaviors in adolescent mice including SPT and EPM results. Fecal microbial composition differed in the CON+saline, CUMS+saline, and CUMS+inosine groups, which were characterized by 126 discriminative amplicon sequence variants belonging to Bacteroidetes and Firmicute at the phylum level and Muribaculaceae and Lachnospiraceae at the family level. Muribaculaceae was positively associated with depressive and anxiety-like behaviors. KEGG functional analysis suggested that inosine might affect gut microbiota through carbohydrate metabolism and lipid metabolism pathways. The results of the study indicated that inosine improved depressive and anxiety-like behaviors in adolescent mice, in conjunction with the alteration of fecal microbial composition. Our findings may provide a novel perspective on the antidepressant effects of inosine in children and adolescents.

目前的抗抑郁药并没有为患有重度抑郁症 (MDD) 的儿童和青少年带来明显的优势。越来越多的证据强调了肌苷对成人 MDD 的潜在抗抑郁作用，肠道微生物组与 MDD 显着相关通过微生物群-肠-脑轴。然而，很少有研究调查肌苷与 MDD 青少年肠道微生物群之间可能的关联。目前的研究调查了肌苷对青春期雄性 C57BL/6 小鼠的潜在抗抑郁作用。经过 4 周的慢性不可预测的轻度应激 (CUMS) 刺激后，通过体重、蔗糖偏好测试 (SPT)、旷场测试和高架十字迷宫 (EPM) 对小鼠进行评估。通过16S rRNA基因测序确定粪便的微生物群组成。肌苷显着改善了青春期小鼠 CUMS 诱导的抑郁和焦虑样行为，包括 SPT 和 EPM 结果。CON+盐水组、CUMS+盐水组和CUMS+肌苷组的粪便微生物组成不同，其特征在于126个有区别的扩增子序列变体属于拟杆菌 和 厚壁菌 在门级和 木兰科 和 毛螺科 在家庭层面。 木兰科与抑郁和焦虑样行为呈正相关。KEGG 功能分析表明，肌苷可能通过碳水化合物代谢和脂质代谢途径影响肠道微生物群。研究结果表明，肌苷改善了青春期小鼠的抑郁和焦虑样行为，同时改变了粪便微生物组成。我们的研究结果可能为肌苷对儿童和青少年的抗抑郁作用提供新的视角。