Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Key Laboratory of Immunity and Metabolism, Department of Pathogen Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
The Second Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Gut Microbes. 2024 Jan-Dec;16(1):2391535. doi: 10.1080/19490976.2024.2391535. Epub 2024 Aug 25.
Chronic infection with the neurotropic parasite can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear.
C57BL/6J mice were infected with 10 cysts of Antibiotic depletion of gut microbiota and fecal microbiota transplantation experiments were utilized to investigate the causal relationship between gut microbiota and anxiety. Anxiety-like behaviors were examined by the elevated plus maze test and the open field test; blood, feces, colon and amygdala were collected to evaluate the profiles of serum endotoxin (Lipopolysaccharide, LPS) and serotonin (5-hydroxytryptamine, 5-HT), gut microbiota composition, metabolomics, global transcriptome and neuroinflammation in the amygdala. Furthermore, the effects of Diethyl butylmalonate (DBM, an inhibitor of mitochondrial succinate transporter, which causes the accumulation of endogenous succinate) on the disorders of the gut-brain axis were evaluated.
Here, we found that chronic infection induced anxiety-like behaviors and disturbed the composition of the gut microbiota in mice. In the amygdala, infection triggered the microglial activation and neuroinflammation. In the colon, infection caused the intestinal dyshomeostasis including elevated colonic inflammation, enhanced bacterial endotoxin translocation to blood and compromised intestinal barrier. In the serum, infection increased the LPS levels and decreased the 5-HT levels. Interestingly, antibiotics ablation of gut microbiota alleviated the anxiety-like behaviors induced by infection. More importantly, transplantation of the fecal microbiota from -infected mice resulted in anxiety and the transcriptomic alteration in the amygdala of the antibiotic-pretreated mice. Notably, the decreased abundance of succinate-producing bacteria and the decreased production of succinate were observed in the feces of the -infected mice. Moreover, DBM administration ameliorated the anxiety and gut barrier impairment induced by infection.
The present study uncovers a novel role of gut microbiota in mediating the anxiety-like behaviors induced by chronic infection. Moreover, we show that DBM supplementation has a beneficial effect on anxiety. Overall, these findings provide new insights into the treatment of -related mental disorders.
神经嗜性寄生虫 的慢性感染会导致宿主焦虑和肠道微生物群落失调。然而，寄生虫引起焦虑的肠道微生物群落的潜在作用尚不清楚。
用 10 个 包囊感染 C57BL/6J 小鼠；利用抗生素耗尽肠道微生物群落和粪便微生物移植实验来研究肠道微生物群落与焦虑之间的因果关系。通过高架十字迷宫测试和旷场测试来检测焦虑样行为；采集血液、粪便、结肠和杏仁核，评估血清内毒素（脂多糖，LPS）和血清素（5-羟色胺，5-HT）、肠道微生物群落组成、代谢组学、全局转录组和杏仁核中的神经炎症谱。此外，还评估了二乙基丁烯二酸酯（DBM，一种抑制线粒体琥珀酸转运体的抑制剂，导致内源性琥珀酸积累）对肠道-大脑轴紊乱的影响。
我们发现，慢性感染会引起小鼠的焦虑样行为，并扰乱肠道微生物群落的组成。在杏仁核中，感染引发小胶质细胞激活和神经炎症。在结肠中，感染引起包括结肠炎症升高、细菌内毒素向血液易位增强和肠道屏障受损的肠道失调。在血清中，感染增加了 LPS 水平，降低了 5-HT 水平。有趣的是，抗生素耗尽肠道微生物群落可减轻 感染引起的焦虑样行为。更重要的是，将来自感染小鼠的粪便微生物群移植到抗生素预处理小鼠中，导致抗生素预处理小鼠的焦虑和杏仁核转录组改变。值得注意的是，在感染小鼠的粪便中观察到琥珀酸产生菌的丰度降低和琥珀酸产量降低。此外，DBM 给药可改善 感染引起的焦虑和肠道屏障损伤。
本研究揭示了肠道微生物群落在介导慢性 感染引起的焦虑样行为中的新作用。此外，我们表明 DBM 补充剂对焦虑有有益的作用。总的来说，这些发现为治疗与 相关的精神障碍提供了新的见解。
