Digestive Profiles of Human Milk, Recombinant Human and Bovine Lactoferrin: Comparing the Retained Intact Protein and Peptide Release.

Lactoferrin (LF) is a major component of human milk. LF supplementation (currently bovine) supports the immune system and helps maintain iron homeostasis in adults. No recombinant human lactoferrin (rhLF) is available for commercial food use. To determine the extent to which rhLF (Effera™) produced by Komagataella phaffii digests similarly to hmLF, a validated in vitro digestion protocol was carried out. Bovine LF (bLF) was used as an additional control, as it is approved for use in various food categories. This study compared the extent of intact protein retention and the profile of peptides released in hmLF, bLF and rhLF (each with low and high iron saturation) across simulated adult gastric and intestinal digestion using gel electrophoresis, ELISA and LC-MS. Intact LF retention across digestion was similar across LF types, but the highest iron-saturated hmLF had greater retention in the simulated gastric fluid than all other sample types. Peptides identified in digested hmLF samples strongly correlated with digested rhLF samples (0.86 < r < 0.92 in the gastric phase and 0.63 < r < 0.70 in the intestinal phase), whereas digested bLF samples were significantly different. These findings support the potential for rhLF as a food ingredient for human consumption.

Context-dependent activation of a social behavior brain network associates with learned vocal production.

In zebra finches, an avian brain network for vocal control undergoes context-dependent patterning of song-dependent activation. Previous studies in zebra finches also implicate the importance of dopaminergic input in producing context-appropriate singing behavior. In mice, it has been shown that oxytocinergic neurons originated in the paraventricular nucleus of the hypothalamus (PVN) synapse directly onto dopamine neurons in the ventral tegmental area (VTA), implicating the necessity of oxytocin signaling from the PVN for producing a context-appropriate song. Both avian and non-avian axonal tract-tracing studies indicate high levels of PVN innervation by the social behavior network. Here, we hypothesize that the motivation for PVN oxytocin neurons to trigger dopamine release originates in the social behavior network, a highly conserved and interconnected collection of six regions implicated in various social and homeostatic behaviors. We found that expression of the neuronal activity marker EGR1 was not strongly correlated with song production in any of the regions of the social behavior network. However, when EGR1 expression levels were normalized to the singing rate, we found significantly higher levels of expression in the social behavior network regions except the medial preoptic area during a social female-directed singing context compared to a non-social undirected singing context. Our results suggest neuronal activity within the male zebra finch social behavior network influences the synaptic release of oxytocin from PVN onto dopaminergic projection neurons in the VTA, which in turn signals to the vocal control network to allow for context-appropriate song production.