In our recent report [15], we performed pathogen challenges of the digestive tract of a transgenic milk-fed animal model to test if porcine LF (pLF) is an effective SDD regimen. Transgenic mice expressed recombinant LF in their milk at 120 ± 13.6 mg/L during the lactation stage and fed normal CD-1 mice pups for 4 weeks. The pups were subsequently challenged with pathogenic Escherichia coli, Staphylococcus aureus and Candida albicans. The groups that were fed pLF transgenic milk demonstrated statistically significant improvements in weight gain, lower bacterial numbers in intestinal fluid, blood and liver, and healthier microvilli in the small intestinal tissue, lower proinflammatory cytokines when compared to the control groups that were fed normal milk. Results showed that recombinant pLF expressed in the milk of transgenic mice and fed to mice pups led to broad spectrum antimicrobial activity in the digestive tract and protected the mucosa of the small intestine from injury, implying that porcine LF can be used as an effective selective decontaminant of the digestive tract.