Gut microbiota mediates anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice
Xiaotong Luo,
Xiaoying Yang,
Shimin Tan,
Yongsheng Zhang,
Yunqiu Liu,
Xiaokang Tian,
Yingting Huang,
Yuying Zhou,
Cheng He,
Kun Yin,
Daxiang Xu,
Xiangyang Li,
Fenfen Sun,
Renxian Tang,
Jianping Cao,
Kuiyang Zheng,
Yinghua Yu,
Wei Pan
Affiliations
Xiaotong Luo
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
Xiaoying Yang
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
Shimin Tan
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
Yongsheng Zhang
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
Yunqiu Liu
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
Xiaokang Tian
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
Yingting Huang
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
Yuying Zhou
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
Cheng He
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
Kun Yin
Shandong Institute of Parasitic Diseases, Shandong First Medical University & Shandong Academy of Medical Sciences, Jining, Shandong, China
Daxiang Xu
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
Xiangyang Li
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
Fenfen Sun
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
Renxian Tang
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
Jianping Cao
National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Centre for Tropical Diseases, Shanghai, China
Kuiyang Zheng
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
Yinghua Yu
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
Wei Pan
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
Background 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.Methods 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.Results 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.Conclusions 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.
