The bacteria in our intestines affect our body in a variety of ways. They train our immune system, influence metabolic processes and may even have an impact on our mental health. But how does the intestinal microbiome communicate with our body? Researchers have now found this out in mice. According to this, intestinal bacteria package their metabolic products in small membrane vesicles, so-called vesicles, and allow them to be transported throughout the body via the bloodstream. In this way, the bacterial biomolecules reach various organs and can even cross the blood-brain barrier.
Billions of bacteria colonize our intestines and form the so-called intestinal microbiome. It is estimated that there are 1.3 bacterial cells for every human cell in the body and all intestinal bacteria together have around 150 times as many genes as we do. The gene products of our microbiome interact through direct contact with the cells of our intestinal mucosa, but also have an effect far beyond the intestine. However, how they reach distant organs such as the liver, kidneys or brain has so far been unclear. One hypothesis was that bacterial metabolic products such as proteins and hereditary RNA molecules are distributed through the bloodstream in the body via vesicles.
Red glow as a marker
A team led by Miriam Bittel from the University of Erlangen-Nuremberg has now confirmed this hypothesis. In order to be able to trace the path of the bacterial biomolecules in the body, they used a trick: They used mice that were genetically manipulated in such a way that they possessed a gene that is activated upon contact with a certain gene scissors and produces a glowing red protein. They colonized the intestines of these mice with E. coli bacteria, which produced these gene scissors. Body cells of the mouse that came into contact with the bacterially produced gene scissors began to fluoresce red and were thus easily identifiable.
The result: “We observed a red fluorescence in the cells along the intestinal epithelium, including intestinal stem cells and immune cells of the mucous membrane such as macrophages,” the researchers report. “In addition, the bacterially produced gene scissors also induced activation of the marker gene in a large number of tissues, including the heart, liver, kidneys, spleen and brain, far outside the intestine.” Bittel and her colleagues were also able to demonstrate under the electron microscope that the E. .coli bacteria actually packaged the gene products in vesicles with a size of 50 to 150 nanometers. Tests on cell cultures also showed that the vesicles can fuse with the host cells via various mechanisms and thus deliver their contents.
Vesicles as a shuttle system
“Taken together, our results provide a method and fundamental proof that vesicles can serve as a biological shuttle system for the transfer of functional biomolecules between bacteria and host cells of mammals,” the researchers say. Co-author Stefan Momma from the Goethe University in Frankfurt am Main comments: “It is particularly impressive that the vesicles of the bacteria also cross the blood-brain barrier and in this way can get into the otherwise very well isolated brain. And the fact that the bioactive bacterial substances were even absorbed by stem cells in the intestinal mucosa shows us that intestinal bacteria can possibly even permanently change the properties of the intestinal mucosa. “
From the point of view of the researchers, their research method could help to better understand the influence of intestinal bacteria on diseases. The new findings on the distribution of vesicles in the body could also be used therapeutically and diagnostically: “Vesicles are in the pipeline as novel, intelligent drug carriers for the targeted administration of drugs, as biomarkers in diagnostics and early cancer detection, and as a promising instrument for development of vaccines, ”the researchers said. “Our study provides fundamental new information about the cellular targets of vesicles throughout the host system, which is of particular interest in order to better assess the biological scope of such novel therapies.”
Source: Miriam Bittel (University of Erlangen-Nürnberg) et al., Journal of Extracellular Vesicles, doi: 10.1002 / jev2.12159