Mare's and cow's milk: promote similar metabolic effects and expression of innate markers in Caco-2 cells?

• The digestion resistant peptides in mare's and cow's milk are compared for the first time.
• Fewer proteolytic resistant peptides were absorbed from mare's milk than from cow's milk.
• The metabolic effect of mare's milk and cow's milk on Caco-2 cells was similar.
• Both types of milk increased TNF-α and decreased Il-1β expression (mRNA) in Caco-2 cells.
• Mare's milk, but not cow's milk, increased NFκB expression (mRNA) in Caco-2 cells.

Mare's milk (MM) is very similar to human breast milk, as it consists of low concentrations of proteins and fat and high concentrations of lactose. Thus, MM can be considered as an alternative to cow's milk (CM) for human nutrition. In this study, proteolytic resistant peptides to gastrointestinal enzymes were measured by reverse phase-high-performance liquid chromatography (RP-HPLC-PDA-UV) to determine their relative uptake by intestinal epithelial (Caco-2) cells. Alterations in mitochondrial enzyme activities (MTT test), inner mitochondrial membrane potential (ΔΨm), cell cycle progression and the expression (mRNA) of inflammatory (IL-1β, TNF-α and NF-κB) markers were studied. This is the first study comparing the effects of proteolytic resistant peptides from the whey proteins of mare's milk to those originating from cow's milk on intestinal cells. Similar proteolytic resistant peptide patterns, but lower uptake rates, were observed for MM peptides (7–40%) compared to peptides from CM (40–60%), although both types of peptides, probably derived from α-lactalbumin, were still capable of impairing ΔΨm in intestinal cells (CM > MM).Both MM and CM increased the expression of TNF-α, whereas IL-1β levels were not affected. CM increased NF-κB mRNA levels. Overall, our data indicate that proteolytic resistant peptides from both MM and CM exert similar metabolic effects on mitochondrial metabolism (up to 30%) in intestinal Caco-2 cells. However, the low uptake rates of peptides from MM may be beneficial to the human diet, an alternative to CM. Further in vivo studies are needed to better understand the potential clinical relevance of the control and/or regulation of metabolic processes related to perturbations in the gut immune system associated with lymphoid tissue.