Milk phospholipid supplementation mediates colonization resistance of mice against Salmonella infection in association with modification of gut microbiota.

Gut microbiota-mediated colonization resistance against enteropathogens is known to be greatly influenced by bioactive food compounds. This work aims to investigate the effects of milk phospholipid (MP) supplementation on the colonization resistance of mice to Salmonella enterica serovar Typhimurium (S. Typhimurium) infection, with the focus mainly on the change of gut microbiota. Comparative microbiota analysis based on 16S rRNA gene sequence data of mice under different MP supplementation situations allowed us to identify specific microbiota characteristics associated with the varying degree of susceptibility to S. Typhimurium infection. We found that a moderate dietary intake of MPs (0.05 wt%) significantly increased the relative abundance of Bacteroides spp. (p < 0.05) and the propionate level (p < 0.05) in the mouse colon and enhanced colonization resistance against S. Typhimurium infection, when compared with the un-supplemented S. Typhimurium-infected mice, whereas excessive MP supplementation (0.25 wt%) did not significantly change the level of Bacteroides spp. (p > 0.05) and propionate (p > 0.05) and even enhanced the susceptibility and severity of S. Typhimurium infection. Furthermore, the inhibitory effects of Bacteroides spp. and propionate on S. Typhimurium intestinal colonization were verified in an ex vivo S. Typhimurium-infected 3D colonoid culture system. Our results showed that the supplementation of nutraceuticals may not always be the more the better, particularly under specific pathological conditions, and identification of specific gut microbiota characteristics may have the potential to become an indicator of appropriate supplementation in specific cases.