The mechanism of in vivo bacteriostasis of bovine lactoferrin.

Recently we have reported that orally administered bovine Lf(bLf) exerts bacteriostatic effects against bacterial overgrowth in the intestine of specific-pathogen-free (SPF) mice fed milk. In this animal model, the in vivo bacteriostatic effect of bLf against the proliferation of intestinal Enterobacteriaceae, the bacteria most sensitive to bLf, was independent of the iron-chelating ability of bLf. In addition various proteolytic hydrolysates of bLf (with differing antibacterial activities in vitro) showed the same bacteriostatic effect as undigested bLf. These results suggest that the mechanism of in vivo bacteriostasis of Lf differs from the in vitro mechanism reported. In SPF mice fed milk differing in concentrations of lactose, glucose and galactose, the proliferation of intestinal Enterobacteriaceae was dependent on the carbohydrate concentration in the diet. The addition of 2% bLf to the diets significantly suppressed this carbohydrate-dependent proliferation of bacteria except in the case of diets containing excess carbohydrate. In germ-free mice fed sterile milk, the addition of 2% bLf to milk resulted in a significant decrease in concentrations of lactose, glucose and galactose in the cecal contents. In an in vitro assay system using everted sacs of the small intestine of SPF mice, both bLf and its pepsin hydrolysate apparently stimulated glucose absorption. Based on these findings, we propose that the in vivo mechanism of action of ingested bLf involves the stimulation of carbohydrate absorption resulting in a bacteriostatic effect against Enterobacteriaceae in the intestine of mice fed milk.