Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns

Exosomes participate in cell-to-cell communication, facilitated by the transfer of RNAs, proteins and lipids from donor to recipient cells. Exosomes and their RNA cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as the inter-species transfer of exosomes and RNAs in bovine milk to humans.

Here, researchers from University of Nebraska-Lincoln assessed the bioavailability and distribution of exosomes and their microRNA cargos from bovine, porcine and murine milk within and across species boundaries. Milk exosomes labeled with fluorophores or fluorescent fusion proteins accumulated in liver, spleen and brain following suckling, oral gavage and intravenous administration in mice and pigs. When synthetic, fluorophore-labeled microRNAs were transfected into bovine milk exosomes and administered to mice, distinct species of microRNAs demonstrated unique distribution profiles and accumulated in intestinal mucosa, spleen, liver, heart or brain. Administration of bovine milk exosomes failed to rescue Drosha homozygous knockout mice, presumably due to low bioavailability or lack of essential microRNAs.

Absorption of bovine milk exosomes in mice

(a) DiR-labeled exosomes (1 × 10¹²/g body weight) 3, 6 and 24 hours after intravenous injection in whole Balb/c mice (upper panels) and excised tissues (lower panels). (b) Densitometry analysis of fluorescence in excised tissues 3, 6 and 24 hours after intravenous injection of DiR-labeled exosomes. (c) Fluorescence in Balb/c mice 3, 6, 18, 24 or 48 hours after oral gavage of DiR-labeled (right mouse) or unlabeled exosomes (left mouse; 1 × 10¹²/g body weight). (d) Fluorescence in excised organs of Balb/c mice 3, 6, 18, 24 or 48 hours after oral gavage of free DiR, unlabeled or DiR-labeled exosomes (1 × 10¹²/g body weight). (e) Densitometry analysis of fluorescence in excised tissues after oral gavage of unlabeled or DiR-labeled exosomes at 24 hours, normalized for plate background for each mouse analyzed. (f) Dose-response analysis of fluorescence in excised murine tissues 24 h after intravenous injection with unlabeled or DiR-labeled exosomes (1 × 10¹⁰/g, 1 × 10¹¹/g, 1 × 10¹²/g body weight). (g) Densitometry analysis of excised tissues after intravenous injection of unlabeled or DiR-labeled exosomes for each mouse analyzed (1 × 10¹⁰/g, 1 × 10¹¹/g, 1 × 10¹²/g body weight). (h) Dose-response analysis of fluorescence in excised murine tissues 24 h after oral gavage with unlabeled or DiR-labeled exosomes (1 × 10¹¹/g, 1 × 10¹²/g body weight) 24 h after oral gavage. (i) Densitometry analysis of excised tissues after oral gavage of unlabeled or DiR-labeled exosomes in dose-response experiments. Panels in this figure were assembled from multiple independent images and gels; individual images in the grouped figure are separated by white space.