New insights into the systemic effects of oral lactoferrin: transcriptome profiling.

The immunomodulatory nature of lactoferrin (LF) derives from its ability to bridge innate and adaptive immunity in obtaining physiological equilibrium. LF is an attractive molecule for treatment of diseases that compromise immune homeostasis. Oral delivery is a preferable method for LF administration; however, its bioavailability is affected by protein degradation and absorption. The aim of this study was to evaluate the systemic effects of orally and intravenously (IV) administered recombinant human LF (rhLF) on blood cell transcriptome profiling. Rats were administered a single dose of rhLF by gavage or IV. The transcriptome profiles from the control and the rhLF-treated rats after 3, 6, and 24 h were analyzed using a Clariom D microarray. The results showed differentially expressed genes in response to IV as well as oral administered rhLF including coding and noncoding RNAs. Moreover, a comparison of the differentially expressed genes between oral and IV administration of LF, after 6 h, revealed that the majority (72.8%) of the genes altered in response to oral administration of rhLF were the same as for the IV treatment. The pathway profiles showed similarities in up-regulation of specific genes involved in oxidative stress and inflammatory responses for both routes of treatments. These findings provide evidence of the systemic signal transduction effects of orally administered rhLF.