Vitamin D influences gut microbiota and acetate production in zebrafish (Danio rerio) to promote intestinal immunity against invading pathogens

Although evidence has shown that vitamin D (VD) influences gut homeostasis, limited knowledge is available how VD regulates intestinal immunity against bacterial infection. In the present study, cyp2r1 mutant zebrafish, lacking the capacity to metabolize VD, and zebrafish fed a diet devoid of VD, were utilized as VD-deficient animal models. Our results confirmed that the expression of antimicrobial peptides (AMPs) and IL-22 was restrained and the susceptibility to bacterial infection was increased in VD-deficient zebrafish. Furthermore, VD induced AMP expression in zebrafish intestine by activating IL-22 signaling, which was dependent on the microbiota. Further analysis uncovered that the abundance of the acetate-producer Cetobacterium in VD-deficient zebrafish was reduced compared to WT fish. Unexpectedly, VD promoted the growth and acetate production of Cetobacterium somerae under culture in vitro. Importantly, acetate treatment rescued the suppressed expression of beta-defensins in VD-deficient zebrafish. Finally, neutrophils contributed to VD-induced AMP expression in zebrafish. In conclusion, our study elucidated that VD modulated gut microbiota composition and production of short-chain fatty acids (SCFAs) in zebrafish intestine, leading to enhanced immunity.

Automated summary

This study used cyp2r1 mutant zebrafish and zebrafish fed a VD-deficient diet as VD-deficient animal models to investigate the role of VD in intestinal immunity against bacterial infection. The results showed that VD deficiency decreased the expression of antimicrobial peptides and IL-22, and increased susceptibility to bacterial infection in zebrafish. VD regulated gut microbiota composition and short-chain fatty acid production in the zebrafish intestine, leading to enhanced immunity.