In-depth insights into the disruption of the microbiota-gut-blood barrier of model organism (Bombyx mori) by fluoride

Abstract

Fluoride is a serious health risk to animals and humans. The microbiota-gut-blood barrier (MGBB) plays an indispensable role in maintaining the systematic homeostasis of host organisms. However, the toxic effects of fluoride on MGBB of organisms have not been extensively investigated. Here, we used the silkworm interspecies model to explore the adverse effects of fluoride on the gut microbiota and intestinal tissue and circulating metabolites of organisms. Results showed that fluoride exposure significantly declined the body weight gain and survival rate of organisms and evidently damaged intestinal epithelial cells. In addition, fluoride altered the composition and abundance of intestinal microbiota, which was accompanied by changing gene expression levels of antimicrobial peptides in intestinal tissue. Shifts in the relative abundance of Enterococcus, Aquabacterium, Aureimonas and Methylobacterium in the gut had significant correlations with the concentrations of certain differential metabolites (e.g., amino acids, nucleotides, and nucleotide derivatives) in the bloodstream. Moreover, most circulating metabolites in related nucleotide metabolism pathways were upregulated, whereas those in the pathways of amino acid metabolism were downregulated. This study deepens our understanding of the disruptive effect of fluoride on the MGBB of host organisms and may provide a new insight into the preventive therapy of fluoride-induced diseases.

Keywords: Amino acid metabolism; Beneficial microbes; Fluoride; Interspecies model organism; Microbiota-gut-blood barrier; Multi-omics datasets; Nucleotide metabolism.