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

Abstract

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.

Milk Bioactive Compounds and Gut Microbiota Modulation: The Role of Whey Proteins and Milk Oligosaccharides

“…However, regardless of the mechanisms involved, the results obtained from testing different experimental conditions indicated that the direct prebiotic activity of lactoferrin may vary depending on factors such as bacterial strain, temperature, oxygen levels, lactoferrin iron-saturation levels, and dosage [ 138 , 139 , 140 , 141 , 142 ]. Chen et al, while exploring in vitro the prebiotic potential of bovine lactoferrin in 14 probiotics, including B. breve , L. coryniformis , L. delbrueckii , L. acidophilus , B. angulatum , B. catenulatum , and L. paraplantarum , observed a negligible effect on probiotic growth at 37 °C, but a strong lactoferrin-mediated dose-dependent restart of growth at lower temperatures (i.e., 22 °C), suggesting that the direct prebiotic effects of lactoferrin become significant when the probiotic growth is retarded by cold stress conditions [ 143 ].…”

Evaluation of a Standard Dietary Regimen Combined with Heat-Inactivated Lactobacillus gasseri HM1, Lactoferrin-Producing HM1, and Their Sonication-Inactivated Variants in the Management of Metabolic Disorders in an Obesity Mouse Model

“…Lactoferrin (LF) is an 80 kDa iron-binding glycoprotein predominantly found in the milk and various exocrine fluids of mammals. It manifests diverse pleiotropic activities, encompassing anti-inflammatory, antimicrobial, antioxidant, immune-regulating, and prebiotic properties [28][29][30]. Additionally, in both low-and high-dose combinations, LF and inulin have demonstrated an additive or supra-additive effect in reducing energy intake, body weight, and adiposity in a diet-induced obese rat model [31].…”