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

BACKGROUND

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.