Background: Antibiotic administration can result in gut microbiota and immune system alterations that impact health. Bovine lactoferrin is a milk protein with anticancer, anti-inflammatory, antimicrobial and immune modulatory activities. The aim was to study the ability of native and iron-saturated lactoferrin to reverse the effects of clindamycin on gut microbiota and intestinal Toll-like receptor (TLR) expression in a murine model. Methods: Male C57BL/6 mice were treated with vehicle, clindamycin (Clin), native bovine lactoferrin (nLf), nLf + clindamycin (nLf_Clin), iron-saturated bovine lactoferrin (sLf) and sLf + clindamycin (sLf_Clin). Fecal samples of each group were collected, and bacterial DNA was extracted. Sequencing of 16s rRNA V4 hypervariable gene regions was conducted to assess the microbial composition. mRNA expression levels of TLRs (1–9) were determined in mouse colon by qPCR. Pearson's correlation test was carried out between bacteria showing differences in abundance among samples and TLR2, TLR8 and TLR9. Results: Beta-diversity analysis showed that the microbial community of the vehicle was different from the communities of Clin, nLf_Clin and sLf_Clin. At the family level, Bacteroidaceae, Prevotellaceae and Rikenellaceae decreased in the Clin group, and treatment with nLf or sLf reverted these effects. Clin reduced the expression of TLR2, TLR8 and TLR9 and sLf reverted the decrease in the expression of these receptors. Finally, TLR8 was positively correlated with Rikenellaceae abundance. Conclusion: In a situation of intestinal dysbiosis induced by clindamycin, lactoferrin restores the normal levels of some anti-inflammatory bacteria and TLRs and, therefore, could be a good ingredient to be added to functional foods.

Milk contains bioactive molecules with important functions as defensive proteins; among them are the whey protein lactoferrin and proteins of the milk fat globule membrane (MFGM) present in buttermilk. The aim of this study has been to investigate the effects of lactoferrin, whey, and buttermilk as modulators of intestinal innate immunity and oxidative stress on intestinal epithelial cells, to evaluate its potential use for the development of functional foods. The mRNA expression levels of innate immune system Toll-like receptors (TLR2, TLR4, and TLR9), lipid peroxidation (malondialdehyde + 4-hydroxyalkenals) and protein expression levels of carbonyl were analyzed in enterocyte-like Caco-2/TC7 cells treated for 24 h with different concentrations of lactoferrin, whey, or buttermilk. None of the substances analyzed caused oxidative damage; however, whey significantly decreased the levels of lipid peroxidation. Furthermore, both lactoferrin and whey reduced the oxidative stress induced by lipopolysaccharide. With respect to TLR receptors, lactoferrin, whey, and buttermilk specifically altered the expression of TLR2, TLR4, and TLR9 receptors, with a strong decrease in the expression levels of TLR4. These results suggest that lactoferrin, whey, and buttermilk are potentially interesting ingredients for functional foods because they seem to modulate oxidative stress and the inflammatory response induced by the activation of TLRs.

Lactoferrin (LF) is a whey protein with various and valuable biological activities. For this reason, LF has been used as a supplement in formula milk and functional products. However, it must be considered that the properties of LF can be affected by technological treatments and gastrointestinal conditions. In this article, we have revised the literature published on the research done during the last decades on the development of various technologies, such as encapsulation or composite materials, to protect LF and avoid its degradation. Multiple compounds can be used to conduct this protective function, such as proteins, including those from milk, or polysaccharides, like alginate or chitosan. Furthermore, LF can be used as a component in complexes, nanoparticles, hydrogels and emulsions, to encapsulate, protect and deliver other bioactive compounds, such as essential oils or probiotics. Additionally, LF can be part of systems to deliver drugs or to apply certain therapies to target cells expressing LF receptors. These systems also allow improving the detection of gliomas and have also been used for treating some pathologies, such as different types of tumours. Finally, the application of LF in edible and active films can be effective against some contaminants and limit the increase of the natural microbiota present in meat, for example, becoming one of the most interesting research topics in food technology.

Milk is a source of proteins with high nutritional value and relevant biological activities. Bioactive milk proteins, like lactoferrin, are important for newborn development and can also be used as ingredients in functional products to improve health. Lactoferrin is essential in infant’s diet, since protects against infections and promotes immune system maturation. Bovine lactoferrin is used to supplement formula milk in order to strengthen baby’s defences against some pathogenic bacteria. Thus, lactoferrin supplemented formula can be a barrier against emergent pathogens, such as Cronobacter sakazakii, which has caused great concern in the last few years. Milk proteins generate bioactive peptides in the digestion process, and it is known that industrial processing can modify their susceptibility to digestion. Treatments such as heating have been shown to denature whey proteins and make them more easily digestible. Therefore, the aim of this study was to analyze the effect of technological treatments and gastrointestinal digestion on the antibacterial activity against C. sakazakii of proteins present in dairy formulas supplemented with lactoferrin. Commercial bovine lactoferrin has been shown to have antibacterial activity against C. sakazakii, both in the native state and after static in vitro gastrointestinal digestion. In addition, the digests obtained from dairy formulas subjected to technological treatments, either homogenization or pasteurization, have higher antibacterial activity than non-treated formulas. The release of low molecular weight peptides during the in vitro gastric digestion is probably the cause that would explain the enhanced antibacterial activity of the digested dairy formulas.