Breastmilk is universally celebrated as the unparalleled source of nutrition, tailor-made to meet the complex developmental needs of infants. Beyond its fundamental role in providing essential nutrients, breastmilk is increasingly recognized as a dynamic biological fluid, richly endowed with a diverse array of bioactive components. Among these, the presence of microRNAs (miRNAs) within extracellular vesicles (EVs) has emerged as a riveting frontier in neonatal and maternal health research. These tiny RNA fragments, encapsulated within vesicles, are more than just molecular passengers—they are powerful regulators of gene expression, capable of influencing cellular functions far beyond the infant’s gut.
The study of milk-borne extracellular vesicle microRNAs (EV-miRNAs) has gained particular urgency in the context of the global obesity epidemic. With increasing numbers of mothers entering pregnancy and lactation with overweight or obesity, understanding how these metabolic states affect the biological composition of breastmilk is critical. This new systematic review, published in Pediatric Research, synthesizes pioneering insights into how EV-miRNAs in breastmilk vary in mothers with altered metabolic profiles and what that means for the health trajectories of both mothers and their infants.
At the crux of this research is the concept that breastmilk is not a static nutrient supply but a conveyor belt for molecular signals crafted by the maternal body to guide infant immune development, metabolism, and even neurodevelopment. miRNAs within breastmilk EVs are remarkable in that their lipid bilayer packaging confers resilience against degradation in the harsh digestive milieu of the infant gastrointestinal tract. This protective envelope facilitates their systemic absorption, enabling them to enter the infant’s bloodstream and ultimately target distant organs at the cellular level.
The implications are profound, especially when considering that the miRNA cargo is not a random assortment but a finely tuned collection that reflects the mother’s physiological status. In mothers grappling with overweight or obesity, systemic inflammation, altered lipid profiles, and hormonal imbalances can all influence the miRNA signature in breastmilk EVs. This systematic review highlights how such alterations may impact critical infant developmental pathways including metabolic programming, immune system maturation, and inflammatory responses, potentially predisposing infants to obesity and metabolic syndrome later in life.
Maternal obesity is known to modify the inflammatory milieu systemically, and these inflammatory signals are mirrored in the breastmilk milieu. EV-miRNAs can modulate gene expression in infant tissues involved in inflammation and metabolism, indicating that breastmilk serves not only nutritive but also epigenetic functions. The review meticulously delineates specific miRNAs altered in breastmilk from mothers with overweight or obesity, noting changes that correlate with increased pro-inflammatory signaling or disrupted metabolic regulation in offspring.
It is equally important to acknowledge the bi-directional health impact of breastfeeding on the mother herself. Breastfeeding has been associated with reduced incidences of type 2 diabetes, certain cancers, and postpartum depression. The presence of EV-miRNAs in breastmilk may play a role in these maternal health benefits by potentially modulating maternal systemic inflammation and metabolism. This bidirectional exchange via EV-miRNAs symbolizes the intimate biological dialogue between mother and child, underscoring breastfeeding as a mutual health-promoting process.
Technological advancements in isolating and characterizing EVs from human breastmilk have been a cornerstone in unveiling the complexities of EV-miRNAs. The systematic review presents state-of-the-art methodologies, including ultracentrifugation, nanoparticle tracking, and high-throughput sequencing, which have allowed researchers to catalogue the diverse miRNA profiles. These methodologies further illuminate the nuanced differences seen in maternal overweight and obesity, emphasizing the precision and sensitivity required to capture these subtle shifts in breastmilk composition.
Moreover, the stability of EV-miRNAs during storage and digestive passage offers exciting possibilities for therapeutic applications. Understanding how maternal metabolic health influences the miRNA cargo opens avenues for devising interventions aimed at optimizing milk composition. Potential future therapies could include dietary or pharmacological modulation in lactating mothers targeted at improving the EV-miRNA profile, thereby enhancing infant health outcomes.
Further exploration into the mechanistic pathways by which EV-miRNAs affect infant organogenesis and metabolic programming is a critical next step. The review calls for longitudinal cohort studies combining comprehensive breastmilk EV-miRNA profiling with detailed phenotypic characterization of infant growth and metabolic markers. Such integrated approaches promise to unravel the causal relationships and identify possible biomarkers predictive of disease risk, enabling proactive health strategies.
The cross-disciplinary nature of this research—spanning molecular biology, nutrition, epidemiology, and clinical science—illustrates the complexity inherent in understanding maternal-infant health dynamics. Collaboration is essential to translate these molecular insights into public health policies and clinical guidelines, especially in addressing the rising challenge of maternal obesity worldwide.
Importantly, this systematic review underscores the heterogeneity of EV-miRNA profiles across different populations and ethnic groups. Environmental factors, dietary habits, and genetic diversity all contribute to the variability in breastmilk composition. Future studies must incorporate diverse cohorts to ensure that findings are globally relevant and to tailor interventions appropriately.
The systematic review also raises compelling questions about the impact of breastfeeding duration and exclusivity on the EV-miRNA-mediated health effects. It hints that longer and exclusive breastfeeding could amplify positive miRNA-mediated programming, while early cessation or supplementation with formula could attenuate these benefits. This positions breastfeeding promotion not only as a nutritional priority but as a crucial epigenetic intervention.
In sum, the characterization of extracellular vesicle microRNAs in breastmilk from mothers with overweight and obesity reveals a sophisticated molecular dialogue that shapes the health trajectories of the next generation. These findings highlight a previously underappreciated layer of maternal influence, transmitted via breastmilk, that goes far beyond basic nutrition to orchestrate gene expression patterns affecting metabolism, immunity, and potentially disease susceptibility.
As the obesity epidemic continues to challenge global health frameworks, such insights into breastmilk biology offer a beacon of hope. They empower clinicians, researchers, and policymakers to harness the intricate biology of lactation to mitigate risk and promote resilience in vulnerable infant populations. This review not only advances our scientific understanding but also reinforces the timeless importance of breastfeeding in nurturing both infant and maternal well-being.
Breastfeeding, therefore, stands as one of the most accessible and impactful interventions available—one that operates on the molecular scale through EV-miRNAs, communicating the mother’s health status to the infant and offering the opportunity to shape lifelong health outcomes. With continued research, these tiny RNA molecules may hold the key to unlocking personalized nutritional strategies that support optimal growth and disease prevention from the very earliest moments of life.
Subject of Research: Extracellular vesicle microRNAs in breastmilk of mothers with overweight and obesity and their impact on maternal and infant health outcomes.
Article Title: Extracellular vesicle microRNAs in breastmilk of mothers with overweight and obesity: a systematic review.
Article References:
Ivashkova, A., Ivashkova, V., Lin, L. et al. Extracellular vesicle microRNAs in breastmilk of mothers with overweight and obesity: a systematic review. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04643-4
Image Credits: AI Generated
DOI: 20 December 2025
