Marginal Zinc Deficiency Aggravated Intestinal Barrier Dysfunction and Inflammation through ETEC Virulence Factors in a Mouse Model of Diarrhea

Zinc is both essential and inhibitory for the pathogenesis of enterotoxigenic Escherichia coli (ETEC). However, the accurate effects and underlying mechanism of marginal zinc deficiency on ETEC infection are not fully understood. Here, a marginal zinc-deficient mouse model was established by feeding mice with a marginal zinc-deficient diet, and ETEC k88 was further administrated to mice after antibiotic disruption of the normal microbiota. Marginal zinc deficiency aggravated growth impairment, diarrhea, intestinal morphology, intestinal permeability, and inflammation induced by ETEC k88 infection. In line with the above observations, marginal zinc deficiency also increased the intestinal ETEC shedding, though the concentration of ETEC in the intestinal content was not different or even decreased in the stool. Moreover, marginal zinc deficiency failed to change the host’s zinc levels, as evidenced by the fact that the serum zinc levels and zinc-receptor GPR39 expression in jejunum were not significantly different in mice with ETEC challenge. Finally, marginal zinc deficiency upregulated the relative expression of virulence genes involved in heat-labile and heat-stable enterotoxins, motility, cellular adhesion, and biofilm formation in the cecum content of mice with ETEC infection. These findings demonstrated that marginal zinc deficiency likely regulates ETEC infection through the virulence factors, whereas it is not correlated with host zinc levels