Chronic loneliness is a widespread issue, and the gut-brain axis is known to be crucial in facilitating communication between the gut and brain. However, the precise mechanism by which chronic loneliness affects the gut-brain axis remains uncertain. Fourteen 55-week-old Balb/c mice were used in the experiment, with seven mice being randomly assigned to the chronic social isolation (CSI) group. The CSI group mice underwent 12 weeks of isolation to simulate the psychiatric state of a population in prolonged social isolation. The mental state of the CSI mice was assessed through animal behavior analysis, while plasma cytokines were measured using ELISA. Additionally, the composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the metabolite composition of the intestinal contents was examined using nontargeted metabolomics. The Student-T test was used to determine significant mean differences. Mice that were exposed to the CSI exhibited increased immobility time lengths in forced swimming and hanging tail experiments, and decreased movement lengths and number of times traversing the intermediate region, compared to control mice. Additionally, CSI decreased the abundance of the probiotics Ruminococcaceae, Akkermansiaceae, and Christensenellaceae. Additionally, CSI reduced the production of the metabolites oleamide and tryptophan. Furthermore, IL-1β, IL-4, and IL-6 were significantly increased, while TNF-α was significantly decreased. CSI induces a dysbiotic gut microbiota and the production of neurorelated metabolites, which in turn increase inflammatory responses and result in depressive behaviors in CSI mice. Therefore, these findings suggest that the gut microbiota may serve as a target for the treatment of long-term social isolation-induced mental disorders.

中文翻译：

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长期与社会隔离的小鼠表现出受肠道微生物群调节的抑郁样行为

慢性孤独是一个普遍存在的问题，众所周知，肠脑轴对于促进肠道和大脑之间的沟通至关重要。然而，慢性孤独影响肠脑轴的确切机制仍不清楚。实验中使用了 14 只 55 周龄的 Balb/c 小鼠，其中 7 只小鼠被随机分配到慢性社会隔离（CSI）组。 CSI 组小鼠接受了 12 周的隔离，以模拟长期社会隔离人群的精神状态。通过动物行为分析评估CSI小鼠的精神状态，同时使用ELISA测量血浆细胞因子。此外，使用 16S rRNA 测序分析肠道微生物群的组成，并使用非靶向代谢组学检查肠道内容物的代谢物组成。 Student-T 检验用于确定显着的平均差异。与对照小鼠相比，暴露于 CSI 的小鼠在强迫游泳和悬尾实验中表现出增加的不动时间长度，并且减少了运动长度和穿过中间区域的次数。此外，CSI 还降低了益生菌 Ruminococcaceae、Akkermansiaceae 和 Christensenellaceae 的丰度。此外，CSI 还减少了代谢物油酰胺和色氨酸的产生。此外，IL-1β、IL-4和IL-6显着升高，而TNF-α显着降低。 CSI 会诱导肠道微生物群失调以及神经相关代谢物的产生，进而增加炎症反应并导致 CSI 小鼠的抑郁行为。因此，这些发现表明肠道微生物群可以作为治疗长期社会隔离引起的精神障碍的目标。