New research published in the journal Science reports the discovery of a unique pathway by which bacteria in the gut can communicate directly with neurons in the brain responsible for regulating appetite and body temperature. The novel mechanism adds to our growing understanding of gutbrain communication pathways.
One of the most compelling emerging areas in medical science is the connection between the gut and the brain. Recent research has revealed fascinating ways that these two different parts of the body communicate with each other, from the discovery of novel gut cells that can engage neural synapses almost immediately, to the revelation that the gut Certain types of bacteria in the U.S. can affect the activity of immunity. cells in the brain.
Most of these gut-brain discoveries involve bacteria that indirectly affect the brain, such as through releasing molecules that trigger a cascade of other mechanisms. But this new study describes a new way that bacteria can directly modulate the activity of certain groups of neurons.
The research began by examining a type of receptor called NOD2 (nucleotide oligomerization domain). These receptors are normally found on certain immune cells and they respond to the presence of bacterial molecules called muropeptides.
When the bacteria grows, replicates, or dies, it releases these muropeptides from its cell walls. Immune cells depend on NOD2 receptors to detect these muropeptides and keep bacterial populations under control. NOD2 abnormalities have been associated with inflammatory bowel disorders such as Crohn’s disease.
Knowing NOD2 is the key for the body to directly understand these bacterial molecules, the researchers wondered whether any neurons in the brain have NOD2 receptors. Not only did this new study reveal that there are NOD2 receptors expressed by neurons in several regions in the brain, but a high density of NOD2 activity was found specifically in the hypothalamus, a brain region responsible for controlling appetite and body temperature. Responsible for metabolic functions.
In a series of innovative animal experiments, researchers found that muropeptides can directly affect neural activity in areas of the brain that control appetite. Mice engineered to lack NOD2 exhibited rapid weight gain and high susceptibility to metabolic diseases such as type 2 diabetes. Essentially, the research found muropeptides from gut bacteria could not help regulate food intake and body temperature without NOD2 receptors.
To confirm that the bacteria playing this role were muropeptides, the researchers used radioactive tags to track the movement of these molecules. About four hours after feeding the animals these tagged muropeptides, the researchers found that the molecules had moved into the brain and attached to neurons in the hypothalamus.
A visual illustration of the newly discovered communication route
Institut Pasteur / Pascal Marceaud
“It is extraordinary to find that bacterial fragments act strategically directly on a brain center known as the hypothalamus, which is known to manage vital functions such as body temperature, reproduction, hunger and thirst,” said Pierre- said Mary Ledo, a writer. new study.
Interestingly, the researchers noted that the effect of this muropeptide/NOD2 mechanism was most prominent in aged female mice, particularly around six months of age. The study shows that this age span in rats is related to the pre-menopausal period of the human lifespan. It has been hypothesized that hormonal changes in middle-aged women may affect this muropeptide/NOD2 pathway, leading to hot flushes and changes in body weight typical for menopause.
Of course, it’s important to emphasize the general caveat that this research has so far only been done in animals. So more work will be needed to understand whether this same gut-brain pathway plays a similar role in human metabolism.
Nevertheless, this study is an important new contribution to our growing insight into how the gut communicates with the brain. And more specifically, if this NOD2 mechanism is replicated in humans it opens the door for researchers to investigate new ways of treating metabolic disorders.
The new study was published in the journal Science,
Source: Institut Pasteur
