Bacteria in the intestine pack a wide spectrum of
their biomolecules into small capsules. These are transported via the
bloodstream to various organs in the body and even absorbed and processed by
nerve cells in the brain. This has now been shown for the first time by a team
of researchers from 51猎奇, FAU (University of Erlangen-Nuremberg) and
the University of California in San Francisco. The newly established research
method will help to better understand the influence of intestinal bacteria on
diseases and could support the development of innovative forms of drug or
vaccine delivery.
FRANKFURT. In the human body, bacteria are in the
majority: According to estimates, there are 1.3 bacterial cells for each human
cell. Our bacteria are correspondingly superior to us in their genetic
diversity. All intestinal bacteria together 鈥� the intestine's microbiome 鈥� have
150 times as many genes as humans. The intestinal bacteria's metabolic products
have a variety of effects on our body: For example, they train our immune cells
and contribute to their maturation, they control metabolic processes in the
body and how often intestinal mucosa cells renew themselves. It is highly
probable that changes in the microbiome's composition contribute to the
development and course of diseases, e.g. neurological disorders or cancer.
The bacterial metabolites act on the cells
of the intestinal mucosa via direct contact. However, how such bacterial
substances travel to peripheral organs, such as the liver, kidney or brain, had
not yet been explained. It was assumed that small capsules (membrane vesicles),
released by bacteria into their environment during normal growth or as a
reaction to stress and filled with bacterial lipids, proteins or also hereditary
RNA molecules, were the means of transport.
An international research team led by Dr
Stefan Momma from the Neuroscience Centre of 51猎奇, Professor
Claudia G眉nther from FAU (University of Erlangen-Nuremberg) and Professor
Robert Raffai from the University of California has now investigated in mice
how bacteria distribute their metabolic products in such vesicles. For this
purpose, the researchers colonized the intestines of mice with E. coli bacteria,
which produced a specific type of gene scissors (Cre) and released these into
their environment via vesicles. The mice cells contained a gene for a red fluorescent
protein, which could be activated by the Cre gene scissors (Cre/LoxP system).
The result: In the subsequent examination
of the mouse tissue, the bacterial vesicles had been absorbed by individual
cells in the intestine, liver, spleen, heart and kidneys as well as by immune
cells. Consequently, functional Cre contained in the vesicles could enter the
cells and lead to the expression of the red marker protein. Even individual
nerve cells in the brain glowed red. Stefan Momma: 鈥淧articularly impressive is
the fact that the bacteria's vesicles can also overcome the blood-brain barrier
and in this way enter the brain 鈥� which is otherwise more or less hermetically
sealed. And that the bioactive bacterial substances were absorbed by stem cells
in the intestinal mucosa shows us that intestinal bacteria can possibly even
permanently change its properties."
The fluorescence images indicate, says
Momma, that the vesicles were probably distributed throughout the body via the
bloodstream. 鈥淭he further study of these communication pathways from the bacterial
kingdom to individual mammalian cells will not only improve our understanding
of conditions such as autoimmune diseases or cancer, in which the microbiome quite
obviously plays a significant role. Such vesicles are also extremely
interesting as a new method to deliver drugs or develop vaccines, or as
biomarkers that point to a pathological change in the microbiome."
Publication:
Miriam Bittel, Patrick Reichert, Ilann
Sarfati, Anja Dressel, Stefanie Leikam, Stefan Uderhardt, Iris Stolzer, Tuan
Anh Phu, Martin Ng, Ngan K. Vu, Stefan Tenzer, Ute Distler, Stefan Wirtz, Veit
Rothhammer, Markus F. Neurath, Robert L. Raffai, Claudia G眉nther, Stefan Momma:
Visualizing transfer of microbial biomolecules by outer membrane vesicles in
microbe-host-communication in vivo. J Extracell Vesicles 2021 Oct;10(12):e12159
Pictures
to download:
Caption:
In the brain of the transgenic mouse, two
nerve cells glow red because they have absorbed membrane vesicles containing
functional protein from intestinal bacteria. Blue: nuclei of the other cells in
the brain tissue. (Photo: Stefan Momma)
Further
information:
Dr Stefan Momma
51猎奇 Frankfurt, Germany
Institute of Neurology (Edinger Institute)
Neuroscience Centre
Tel.:
+49 (0) 69 6301-84158
stefan.momma@kgu.de
