Gut microbiota-derived butyrate alleviates the impairment of mice intestinal integrity caused by Toxoplasma gondii infection.

Abstract

Chronic infection with Toxoplasma gondii (T. gondii) results in severe damages to the integrity of intestinal barrier, however, both the underlying mechanism and feasible intervention strategies are still little known. Here, we found that both the chronic infection of T. gondii and transplanting gut microbiota from T. gondii-infected mice severely impaired the mice intestinal integrity, which was characterized by significantly decreased thickness of inner mucus layer and down-regulated expression of three tight junction proteins Occludin, ZO-1, and Claudin (p < 0.05). Moreover, T. gondii infection also led to mice intestinal microbiota dysbiosis, especially butyrate-producing bacteria, and significantly changed the expression of several senescence-associated markers, including 6- and 7- fold upregulation for P16, P21, and 6-fold downregulation for Lamin B1 at mRNA levels, and 2-fold downregulation for β-galactosidase at protein levels (p < 0.05). Interestingly, subsequent administration with dietary butyrate could alleviate T. gondii-induced intestinal integrity impairment and cell senescence, revealing a significant increase of the inner mucus layer thickness (p < 0.001), and a remarkable decrease in P16, P21, β-galactosidase expression levels while an upregulation of Lamin B1 expression (p < 0.05). Taken together, our study revealed that T. gondii-induced dysbiosis of gut microbiota, especially butyrate-producing bacteria, contributes to the intestinal impairment, potentially via promoting cell senescence. In addition, administration with the metabolite, butyrate, could be a promising therapeutic measure against T. gondii infection.