Featured Prebiotic Agent: The Roles and Mechanisms of Direct and Indirect Prebiotic Activities of Lactoferrin and Its Application in Disease Control

Lactoferrin (LF) is a glycoprotein found in mammalian milk, and lactoferricin is a peptide derived from LF hydrolysate. Both LF and lactoferricin (LFcin) have diverse functions that could benefit mammals. Bovine LF (BLF) and BLFcin exhibit a wide range of antimicrobial activities, but most probiotic strains are relatively resistant to their antibacterial effects. BLF and BLF hydrolysate can promote the growth of specific probiotics depending on the culture conditions, the dose of BLF or BLF-related peptides, and the probiotic strains used. BLF supplementation has been shown to modulate several central molecular pathways or genes in Lacticaseibacillus rhamnosus GG under cold conditions, which may explain the prebiotic roles of BLF. LF alone or in combination with selected probiotics can help control bacterial infections or metabolic disorders, both in animal studies and in human clinical trials. Various LF-expressing probiotics, including those expressing BLF, human LF, or porcine LF, have been developed to facilitate the combination of LFs with specific probiotics. Supplementation with LF-expressing probiotics has positive effects in animal studies. Interestingly, inactivated LF-expressing probiotics significantly improved diet-induced nonalcoholic fatty liver disease (NAFLD) in a mouse model. This review highlights the accumulated evidence supporting the use of LF in combination with selected LF-resistant probiotics or LF-expressing probiotics in the field.