Researcher: Dr. Daniela Barile, UC Davis

• The aim of this research was to identify novel uses for an undervalued dairy coproduct, Procream, also known as whey protein phospholipid concentrate (WPPC).

• This was the first study to investigate the effects of different Procream fractions on gut health in a mouse model.

• Although the researchers found no significant shifts in the mouse gut microbiota or intestinal permeability, they did see effects related to gut-brain signaling and food intake. The results clearly differentiated the activity of Procream fractions in the mouse model, with the cream fraction showing increased sensitivity to hormones which regulate food intake.

Procream is a co-product of whey protein isolate production and is currently an undervalued dairy product with promising health properties. In another CDRF-funded research project, Procream was found to be a source of milk fat globule membrane (MFGM) and bioactive glycoproteins that could positively impact the gut microbiome.

Earlier studies demonstrated that Procream supplementation was associated with decreased weight gain and improvements in inflammation and memory in animal models. The current study built on this research by providing a more comprehensive characterization of Procream’s lipid and protein fractions and conducting additional mouse studies to determine the impacts of different Procream fractions on the gut microbiome, intestinal barrier function, and markers of gut and systemic inflammation.

To understand which compounds in the protein and lipid fractions of Procream were specifically responsible for the benefits to the host gut microbiome observed in their previous study, the researchers separated Procream into its protein and lipid fractions. Then, within the lipid fraction, the small fat globules were further separated and tested individually. The researchers created four fractions: 1) cream, which was enriched in lipids; 2) skim, that had no milk fat globule particles; 3) retentate or ultrafiltered skim, which was enriched in glycoproteins; and 4) permeate that had non-glycosylated proteins, such as ß-lactoglobulin.

These fractions and the starting material (whole Procream) were each characterized by a comprehensive compositional and proteomics analysis. Using a well-established mouse model of high-fat diet-induced obesity, the researchers investigated the potential beneficial effects of dietary supplementation with various Procream fractions on metabolic phenotype, intestinal barrier function, intestinal inflammation, and microbial dysbiosis. Contrary to the study’s hypothesis, there were no observable changes in the composition of the mouse gut microbiome from any of the Procream fractions.

However, the researchers had a particularly interesting finding when examining the activity of the gut hormone cholecystokinin (CCK). Previous research shows that CCK has the ability to increase satiety. High-fat diets have been shown to impair this signal and lead to chronic overeating. In mice fed a high-fat diet, however, CCK had no effect on food intake. Adding the skim fraction from Procream to the mice’s water also had no effect on CCK’s ability to inhibit food intake in mice on a high-fat diet, but the addition of the cream fraction to the high-fat diet did result in CCK inhibition of food intake. The researchers believe that the cream fraction restored the ability of CCK to decrease food intake due to impacts on the gut-brain axis. This was the first time this effect has been shown with a Procream fraction.

Contrary to the study’s hypothesis, supplementation with Procream fractions had no significant effect on the microbiome or gut permeability. However, supplementation with the cream fraction did result in significant improvements to impaired gut-brain signaling induced by high-fat diets.