Gut microbiota mediates anxiety-like behaviors induced by chronic infection of Toxoplasma gondii in mice

作者：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 · 发表于：Gut Microbes · 年份：2024 · DOI：10.1080/19490976.2024.2391535 · 被引用次数：33 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Toxoplasma gondii Research Studies

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...