How do nutritional EVs survive digestion? Rethinking what happens in the gut 

At the very start of the NutriEV project, one fundamental question challenges conventional nutrition science: what really happens to food-derived extracellular vesicles (nutriEVs) during digestion? 

For decades, digestion has been understood as a largely destructive process, breaking down food into basic molecular building blocks. However, emerging research within NutriEV suggests a more nuanced reality. Rather than being completely degraded, nutriEVs appear to persist through digestion in transformed, yet biologically meaningful forms. 

In this article, Dr Feby Pratiwi (University of Oulu) provides key insights into how digestion reshapes these nanoscale structures and why these matters for understanding nutrition at a deeper level. 

Do nutriEVs really survive digestion? 

The idea that complex biological structures from food could withstand digestion may seem unexpected. Yet experimental evidence suggests that nutriEVs are more resilient than previously assumed. 

After exposure to both gastric and intestinal fluids, many nutriEVs retain their fundamental vesicle structure. This includes: 

• a lipid bilayer membrane,  

• a nanoparticle-like morphology,  

• and detectable molecular cargo, such as plant-derived microRNAs.  

That said, survival does not mean remaining unchanged. NutriEVs undergo measurable alterations in size, surface charge, and abundance. Importantly, however, they are not fully degraded, indicating that digestion does not simply eliminate these structures but transforms them. 

Which stages of digestion matter most? 

Digestion is not a single event but a sequence of biochemical environments, each exerting different pressures on ingested materials. According to Dr Pratiwi, both major stages, gastric and intestinal, play critical roles in shaping nutriEVs. 

• Gastric phase (stomach): 
  The highly acidic environment, combined with protease activity, removes many of the larger vesicles. This results in a relative enrichment of smaller vesicles and changes in their surface charge.  

• Intestinal phase (small intestine): 
  Here, bile salts and pancreatic enzymes further interact with the vesicles. These components remodel membrane lipids and promote the formation of a protein or peptide corona around the vesicles.  

Together, these stages do not simply reduce EV numbers, they actively reshape the vesicle population, producing a distinct post-digestion profile. 

From destruction to transformation: the concept of the “EV digestome” 

“Digestion does not simply destroy nutritional EVs, it reshapes them. What emerges is a transformed population of vesicles that still retain their core structure and can interact with the gut environment.”  

 Dr Feby Pratiwi, UOULU 

One of the most important insights emerging from this work is that digestion should not be viewed as a binary process of survival versus degradation. Instead, it produces a new class of vesicles. 

Dr Pratiwi describes this as the “EV digestome”, the population of nutriEVs that have been modified by digestion but still retain core structural and functional features. 

During this process, EVs: 

• change in size and surface charge,  

• acquire new surface components (such as protein coronas),  

• and experience partial modification of their molecular cargo.  

Crucially, these transformed vesicles are not biologically irrelevant remnants. On the contrary, they are the forms that actually interact with the intestinal environment. 

Why does this matter for nutrition? 

The EV digestome represents the real interface between food-derived vesicles and the human body. These modified EVs are the ones that encounter: 

• intestinal epithelial cells,  

• immune cells,  

• and the gut microbiome.  

This shifts the scientific perspective. Instead of asking whether EVs survive digestion intact, the more relevant question becomes:  what forms of EVs emerge after digestion, and how do they function? 

By focusing on these transformed vesicles, NutriEV is helping to redefine how we understand the biological impact of food, not just as a source of nutrients, but as a carrier of complex, structured information. 

Looking ahead 

Understanding how digestion reshapes nutriEVs is a foundational step for the entire NutriEV project. It sets the stage for investigating how these vesicles: 

• interact with the gut,  

• cross biological barriers,  

• and potentially influence systemic processes.  

In this context, the EV digestome is not just a concept, it is the starting point for exploring how nutrition operates at the nanoscale.