A groundbreaking new study published in Molecular Nutrition & Food Research titled, “Interspecies communication between plant and mouse gut host cells through edible plant derived exosome-like nanoparticles,” reveals a new way that food components ‘talk’ to animal cells by regulating gene expression and conferring significant therapeutic effects. With the recent discovery that non-coding microRNA’s in food are capable of directly altering gene expression within human physiology,[1] this new study further concretizes the notion that the age old aphorism ‘you are what you eat’ is now consistent with cutting edge molecular biology.

Exosomes: The ‘Missing Link’ In How Plants and Animal Cells Communicate and Collaborate

This is the first study of its kind to look at the role of exosomes, small vesicles secreted by plant and animal cells that participate in intercellular communication, in interspecies (plant-animal) communication.

The study explained the biological properties of exosomes as follows:

“Exosomes are produced by a variety of mammalian cells including immune, epithelial, and tumor cells [11–15]. Exosomes play a role in intercellular communication and can transport mRNA, miRNA, bioactive lipids, and proteins between cells [16–19]. Upon contact, exosomes transfer molecules that can render new properties and/or reprogram their recipient cells.”

While most of the research on exosomes has focused on their role in pathological states such as tumor promotion, they were recently found to play a key role in stimulating regeneration within damaged cardiac tissue,[2] and are known to be found in human breast milk, further underscoring how irreplaceable it is vis-à-vis synthesized infant formula.[3]

The New Study

The investigators isolated plant derived exosome-like nanoparticles (EPDENs) from ginger, carrot, grape and grapefruit, and observed their behavior in mammalian cells (mice).

They chose these commonly consumed edible fruits and vegetables because,

“It is well established that a plant-derived diet has great influence on regulation of mammalian host cell homeostasis, in particular, cells in the digestive system [1–3]. Deregulation of plant-derived diet regulated host cell homeostasis leads to increased susceptibility to infections, chronic inflammatory bowel diseases, and cancer [4–10].

They noted, “the cellular and molecular machinery regulating such interspecies mutualism between a plant-derived diet and the mammalian gut is not fully defined.” Their new study aimed to gain new insight into defining the mechanisms through which cross-kingdom crosstalk occurs.

Plant Exosomes Affect Mammalian Cells Intimately

After isolating and characterizing exosome-like nanoparticles from all four edible plants, the researchers discovered they possessed remarkable similarity in size and structure to mammalian-derived exosomes. Furthermore, the study showed “that these exosome-like nanoparticles are taken up by intestinal macrophages and stem cells, and have biological effects on the recipient cells.”

The biological effects were described as follows:

• Ginger exosome-like nanoparticles strongly induced heme oxygenase-1 (HO-1) and IL-10 expressed in macrophages, an indication of anti-inflammatory and antoxidant properties.
• Fruit-derived exosome-like nanoparticles including grape and grapefruit induced Wnt/TCF4 activation, which is a key component of the anti-inflammatory response
• All tested foods activated nuclear translocation of Nrf2, a key regulator of the HO1 gene, which has an important role in anti-inflammation and antioxidation; ginger was found to be most potent, followed by grapefruit, carrot and grape

Notably, EPDENs were found to be resistant to gastric and intestinal enzymatic digestion, further indicating they are capable of exerting significant biological effects by escaping digestive degradation, which has also been found with lectins and microRNA’s within edible foods.

The researchers discussed their results:

“Our findings show that exosome-like nanoparticles are present in edible fruits and vegetables and reveal a previously unrecognized strategy by which plants communicate with mammalian cells via exosome-like nanoparticles in the gut, and in particular intestinal macrophages and stem cells. We found that edible plants contain large amounts of nanoparticles. Like mammalian exosomes, further characterization of the plant nanoparticles led to identifying them as exosome- like nanoparticles based on the nanoparticles being com- posed of proteins, lipids, and miRNAs. EPDENs from different types of plants have different biological effects on the recipient mammalian cells. This finding opens up a new avenue to further study the molecular mechanisms underlying how the plant kingdom crosstalks with mammalian cells such as intestinal macrophages and stem cells via EPDENs. This information may provide the molecular basis of using multiple plant-derived agents for better therapeutic effect than any single plant-derived agent.”

They also offered that their results may explain why those who consume a greater variety of edible plants are healthier:

“It has been known for decades that people eating a variety of edible plants daily are the recipients of many beneficial health effects when compared to subjects that ingest fewer types of edible plants. Ingesting EPDENs from a variety of fruits and vegetables daily would be expected to provide greater beneficial effects for maintaining gut homeostasis than ingesting EPDENs from single edible plant.”