Concentrations of Purine Metabolites Are Elevated in Fluids from Adults and Infants and in Livers from Mice Fed Diets Depleted of Bovine Milk Exosomes and their RNA Cargos.

Background: Humans and mice absorb bovine milk exosomes and their RNA cargos.

Objectives: The objectives of this study were to determine whether milk exosome- and RNA-depleted (ERD) and exosome- and RNA-sufficient (ERS) diets alter the concentrations of purine metabolites in mouse livers, and to determine whether diets depleted of bovine milk alter the plasma concentration and urine excretion of purine metabolites in adults and infants, respectively.

Methods: C57BL/6 mice were fed ERD (providing 2% of the microRNA cargos compared with ERS) and ERS diets starting at age 3 wk; livers were collected at age 7 wk. Plasma and 24-h urine samples were collected from healthy adults who consumed (DCs) or avoided (DAs) dairy products. Spot urine samples were collected from healthy infants fed human milk (HM), milk formula (MF), or soy formula (SF) at age 3 mo. Purine metabolites were analyzed in liver, plasma, and urine; mRNAs and microRNAs were analyzed in the livers of female mice.

Results: We found that 9 hepatic purine metabolites in ERD-fed mice were 1.76 ± 0.43 times the concentrations in ERS-fed mice (P < 0.05). Plasma concentrations and urine excretion of purine metabolites in DAs was ≤1.62 ± 0.45 times the concentrations in DCs (P < 0.05). The excretion of 13 purine metabolites in urine from SF infants was ≤175 ± 39 times the excretion in HM and MF infants (P < 0.05). mRNA expression of 5'-nucleotidase, cytosolic IIIB, and adenosine deaminase in mice fed ERD was 0.64 ± 0.52 and 0.60 ± 0.28 times the expression in mice fed ERS, respectively.

Conclusion: Diets depleted of bovine-milk exosomes and RNA cargos caused increases in hepatic purine metabolites in mice, and in plasma and urine from human adults and infants, compared with exosome-sufficient controls. These findings are important, because purines play a role in intermediary metabolism and cell signaling.