■嗜神经寄生虫弓形虫的慢性感染(T.gondii)可导致宿主焦虑和肠道菌群失调。然而,肠道菌群在寄生虫引起的焦虑中的潜在作用尚不清楚.
■C57BL/6J小鼠感染10个弓形虫囊肿。利用肠道微生物群的抗生素消耗和粪便微生物群移植实验来研究肠道微生物群与焦虑之间的因果关系。通过高架迷宫测试和开放场测试检查了焦虑样行为;血液,粪便,收集结肠和杏仁核以评估血清内毒素(脂多糖,LPS)和5-羟色胺(5-羟色胺,5-HT),肠道菌群组成,代谢组学,杏仁核的整体转录组和神经炎症。此外,丁基丙二酸二乙酯(DBM,线粒体琥珀酸转运蛋白的抑制剂,这导致内源性琥珀酸盐的积累)在肠-脑轴的疾病上进行了评估。
■这里,我们发现弓形虫慢性感染会引起焦虑样行为,并扰乱小鼠肠道菌群的组成。在杏仁核里,弓形虫感染引发了小胶质细胞活化和神经炎症。在结肠里,弓形虫感染引起的肠道畸形包括结肠炎症升高,增强细菌内毒素易位到血液和损害肠屏障。在血清中,弓形虫感染增加了LPS水平,降低了5-HT水平。有趣的是,抗生素对肠道微生物群的消融减轻了弓形虫感染引起的焦虑样行为。更重要的是,从弓形虫感染小鼠的粪便微生物群的移植导致焦虑和抗生素预处理小鼠杏仁核的转录组改变。值得注意的是,在弓形虫感染的小鼠的粪便中观察到产生琥珀酸的细菌的丰度降低和琥珀酸的产生降低。此外,给予DBM改善了弓形虫感染引起的焦虑和肠屏障损害。
■本研究揭示了肠道菌群在介导慢性弓形虫感染引起的焦虑样行为中的新作用。此外,我们表明,DBM补充对焦虑有有益的影响。总的来说,这些发现为弓形虫相关精神障碍的治疗提供了新的见解.
UNASSIGNED: Chronic infection with the neurotropic parasite Toxoplasma gondii (T. gondii) can cause anxiety and gut microbiota dysbiosis in hosts. However, the potential role of gut microbiota in anxiety induced by the parasite remains unclear.
UNASSIGNED: C57BL/6J mice were infected with 10 cysts of T. gondii. 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.
UNASSIGNED: Here, we found that T. gondii chronic infection induced anxiety-like behaviors and disturbed the composition of the gut microbiota in mice. In the
amygdala, T. gondii infection triggered the microglial activation and neuroinflammation. In the colon, T. gondii infection caused the intestinal dyshomeostasis including elevated colonic inflammation, enhanced bacterial endotoxin translocation to blood and compromised intestinal barrier. In the serum, T. gondii infection increased the LPS levels and decreased the 5-HT levels. Interestingly, antibiotics ablation of gut microbiota alleviated the anxiety-like behaviors induced by T. gondii infection. More importantly, transplantation of the fecal microbiota from T. gondii-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 T. gondii-infected mice. Moreover, DBM administration ameliorated the anxiety and gut barrier impairment induced by T. gondii infection.
UNASSIGNED: The present study uncovers a novel role of gut microbiota in mediating the anxiety-like behaviors induced by chronic T. gondii infection. Moreover, we show that DBM supplementation has a beneficial effect on anxiety. Overall, these findings provide new insights into the treatment of T. gondii-related mental disorders.