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The Gut's Secret Messengers

Extracellular vesicles (EVs) derived from the microbiome are one of the most fascinating discoveries in modern science, acting as a "message in a bottle" system at a nanometric scale.

Research Focus: This pioneering research is centered at the University of Oulu and Oulu University Hospital.

These particles are tiny spheres surrounded by a lipid layer that bacteria—both beneficial (probiotics) and harmful (pathogens)—release into their environment (Kaisanlahti et al., 2025). Here is a simple explanation of what they are and why they are so important according to current research:


1. What exactly are EVs?

Imagine that the bacteria in your gut are factories. EVs are the shipping packages that these factories send to the rest of the body. These packages contain valuable information such as proteins, genetic material (RNA and DNA), and chemical messengers. The most surprising part is that, unlike live bacteria which usually stay in the gut, these vesicles are so small that they can cross biological barriers that bacteria cannot, reaching the bloodstream and even the brain (Kaisanlahti, Salmi, et al., 2023).

2. The "EV-biome": A distinct layer of information

Recently, scientists have discovered that the collection of these vesicles (called the "EV-biome" or "communicatome") is not simply a reflection of the bacteria living in the gut. Bacteria carefully select what to send in these packages. This means that to truly understand how our microbiota communicates with us, it is not enough to look at the bacteria; we must study the vesicles separately (Kaisanlahti et al., 2025).

3. Present even before birth

It was once thought that babies were in a completely sterile environment before birth, but it has been discovered that meconium (a baby's first stool) already contains these bacterial vesicles (Turunen et al., 2023). This suggests that the mother sends "messages" via vesicles that cross the placenta to reach the fetus (Kaisanlahti, Turunen, et al., 2023). These messages could serve to "train" the baby's immune system before they are born, preparing them for the outside world.

4. EVs and Probiotics: Messengers of health

Not all bacteria are equal, and the same applies to their vesicles. For example, it has been shown that vesicles from the beneficial bacteria Lactobacillus casei BL23 carry specific proteins (called P40 and P75) that help protect and repair the intestinal lining (BĂ€uerl et al., 2020). This means that much of the benefit of probiotics could be due to these messenger packages rather than the live bacteria alone.

5. Potential as a diagnostic tool

Because these vesicles travel throughout the entire body, scientists believe they could be used as a "liquid biopsy" (Kaisanlahti et al., 2025; Kaisanlahti, Salmi, et al., 2023). By analyzing EVs in blood or urine samples, we could:

6. Beyond Bulk Metagenomics

Current research suggests that EVs provide a more accurate and functional map of host-microbiome interactions than traditional metagenomics. Unlike whole bacteria, EVs represent a selective "communicatome" that can cross biological barriers to act as systemic messengers (Kaisanlahti et al., 2025).

EVs offer a window into metabolic changes and disease markers (such as those following surgery or in inflammatory conditions) that are often invisible in fecal samples. While traditional analysis identifies the microbes present, EV analysis reveals the active dialogue influencing human health (Kaisanlahti et al., 2025).


Key Takeaway

In summary, EVs are the key tool the microbiome uses to influence our systemic health, acting as a vital communication bridge between the microbial world and our own cells.

References

  1. BÀuerl, C., Coll-Marqués, J. M., Tarazona-Gonzålez, C., & Pérez-Martínez, G. (2020). Lactobacillus casei extracellular vesicles stimulate EGFR pathway likely due to the presence of proteins P40 and P75 bound to their surface. Scientific Reports, 10(1).https://doi.org/10.1038/s41598-020-75930-9
  2. Hekkala, J., Kaisanlahti, A., Tejesvi, M. V., Turunen, J., Virtanen, N., Karikka, S., Erawijantari, P. P., Samoylenko, A., Bart, G., Vainio, S., Lahti, L., Hukkanen, J., Ruuska-Loewald, T., Koivukangas, V., & Reunanen, J. (2026). Gut Microbiota-Derived Extracellular Vesicles in Patients With Obesity Undergoing Gastric Bypass Surgery. Molecular Microbiology.https://doi.org/10.1111/mmi.70064
  3. Kaisanlahti, A., Salmi, S., Kumpula, S., Amatya, S. B., Turunen, J., Tejesvi, M., Byts, N., Tapiainen, T., & Reunanen, J. (2023). Bacterial extracellular vesicles – brain invaders? A systematic review. Frontiers in Molecular Neuroscience, 16.https://doi.org/10.3389/fnmol.2023.1227655
  4. Kaisanlahti, A., Turunen, J., Byts, N., Samoylenko, A., Bart, G., Virtanen, N., Tejesvi, M. V., Zhyvolozhnyi, A., Sarfraz, S., Kumpula, S., Hekkala, J., Salmi, S., Will, O., Korvala, J., Paalanne, N., Erawijantari, P. P., Suokas, M., Medina, T. P., Vainio, S., 
 Reunanen, J. (2023). Maternal microbiota communicates with the fetus through microbiota-derived extracellular vesicles. Microbiome, 11(1).https://doi.org/10.1186/s40168-023-01694-9
  5. Kaisanlahti, A., Turunen, J., Hekkala, J., Mishra, S., Karikka, S., Amatya, S. B., Paalanne, N., Kruger, J., Portaankorva, A. M., Koivunen, J., Jukkola, A., Vihinen, P., Auvinen, P., LeppÀ, S., Karihtala, P., Koivukangas, V., Hukkanen, J., Vainio, S., Samoylenko, A., 
 Ruuska-Loewald, T. (2025). Gut microbiota-derived extracellular vesicles form a distinct entity from gut microbiota. MSystems, 10(5).https://doi.org/10.1128/msystems.00311-25
  6. Turunen, J., Tejesvi, M. V., Paalanne, N., Pokka, T., Amatya, S. B., Mishra, S., Kaisanlahti, A., Reunanen, J., & Tapiainen, T. (2024). Investigating prenatal and perinatal factors on meconium microbiota: a systematic review and cohort study. Pediatric Research, 95(1), 135–145.https://doi.org/10.1038/s41390-023-02783-z
  7. Turunen, J., Tejesvi, M. V., Suokas, M., Virtanen, N., Paalanne, N., Kaisanlahti, A., Reunanen, J., & Tapiainen, T. (2023). Bacterial extracellular vesicles in the microbiome of first-pass meconium in newborn infants. Pediatric Research, 93(4), 887–896.https://doi.org/10.1038/s41390-022-02242-1

For Healthcare Professionals & Students

This research represents a paradigm shift in how we understand microbiome-host interactions. The ability of bacterial EVs to cross biological barriers and deliver specific molecular cargo opens new possibilities for:

  • Novel diagnostic approaches using liquid biopsies
  • Targeted therapeutic interventions
  • Understanding probiotic mechanisms of action
  • Early disease detection and prevention strategies