Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

Abstract

Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

Perspectives on Bovine Milk-Derived Extracellular Vesicles for Therapeutic Applications in Gut Health

“…In particular, it was confirmed that EVs and their cargo were not degraded in the harsh digestive environment encountered when milk EVs were ingested (Benmoussa et al, 2016;Izumi et al, 2012;Shandilya et al, 2017;Zeng et al, 2019). It was also confirmed in vitro (Hansen et al, 2020;Izumi et al, 2015;Maburutse et al, 2017;Rani et al, 2017;Roerig et al, 2021;Wolf et al, 2015), in vivo (Kirchner et al, 2020;Manca et al, 2018), or under both conditions (Lopez de Las Munagala et al, 2016) that these EVs and their cargo are taken up (Fig. 1D).…”

Maternal Microbiota, Early Life Colonization and Breast Milk Drive Immune Development in the Newborn

“…Second, an imbalanced absorption of vesicle subpopulations within the colostrum. Other tissues were not analyzed for the presence of milk-derived miRNAs ( 233 ). Hence, the transfer of maternal miRNAs into the neonatal systemic circulation remains elusive and a highly discussed topic, which still needs further investigation.…”