Another area of study that seems to be exploding recently is the relationship between the gut and neurodegeneration. Just 3 months ago, back in November, I wrote about research from Cambridge University which described their finding that the immune system of the brain is directly connected to the immune system of the gut. It was a remarkable discovery: the same antibodies that would protect the gut from invaders were found in the brain. I promised you then to follow that developing story, not thinking that less than 3 months later, I’d be keeping that promise!
New research just published in the very prestigious journal, Nature, describes how a kind of brain cell, the astrocyte, can prevent inflammation, and its activity is modulated by molecules from gut bacteria.[i] Astrocytes are non-neuronal cells that are abundant in the brain and spinal cord and which are known to help maintain the blood-brain barrier as well as regulate the activity of neurons. They also appear to play a significant role in the immunology of the brain, and in the last few years, research has shown that they can trigger inflammation. This new research shows, however, that they can also protect the brain from inflammation.
It turns out that the reason for this duel effect is that not all astrocytes are the same, which is a novel discovery. These scientists found a new kind of astrocyte near the meninges (the membrane which encloses the brain, which I describe in that November post) that express a pair of proteins which signal the destruction of inflammation-promoting rogue cells. The “on” switch for this astrocyte activity stems from bacteria in the gut, which regulate a molecule called interferon-gamma. The lead researcher states, ““Finding microbiome-controlled anti-inflammatory subsets of astrocytes is an important advance in our understanding of CNS inflammation and its regulation…This is a very novel mechanism by which the gut controls inflammation in the brain. It guides new therapies for neurological diseases, and we believe that this mechanism could contribute to the pathogenesis of brain tumors.”[ii]
These scientists believe that this is really only the tip of the iceberg – that many other specific types of astrocytes are yet to be discovered, which are also likely directed by gut flora.
At the same time that this paper came out, a second one was just published by researchers at Washington University in St. Louis, which also looked at immune cells in the meninges. They were trying to find the immune system’s “gateway” into the brain, and noticed that there are vessels which contain fluid leaving the brain which run alongside the sinuses in the dura mater, which is a tough outer layer of the meninges. Dural sinuses contain blood that carries immune cells, and they are not separated by the blood brain barrier.
It turns out that the dural sinuses are filled with molecules from the brain as well as multiple kinds of immune cells – similar to the findings I described 3 months ago. This indicates that essentially, the immune system watches the brain from a distance, and only gets involved when there is a problem. The way the lead researcher describes it: “Imagine if your neighbors went through your trash every day…If they start finding blood-stained towels in your trash, they know something is wrong. It’s the same thing with the immune system. If patrolling immune cells see tumor antigens or signs of infection from the brain, the cells know there’s a problem. They will take that evidence to immune headquarters, which is the lymph nodes, and initiate an immune response.”[iii] Why is this so important? If the location of these inflammatory responses which lead to neurodegeneration has been isolated, there is huge hope that treatments can be developed which target that area, even non-invasively. The lead researcher suggests that since the dura is so close to the skull, ointments may be developed which diffuses through the skull to reach the area.
So all this is especially interesting in terms of tumor development, Alzheimer’s, Parkinson’s disease (PD), multiple sclerosis and more. In fact, in the last few days, I also spotted a press release on the Parkinson’s News Today website, which I read regularly.[iv] A clinical trial is set to take place later this year looking at a treatment to restore the gut microbiome as a treatment for some of the non-motor issues in PD, like constipation. As my regular readers know, the evidence has been rapidly mounting that PD starts in the gut. Unfortunately, the press release doesn’t give any details as to what they will be using to modulate the gut biome, but I will update everyone as soon as more information becomes available. I won’t be at all surprised if it involves butyrate-producing bacteria, in some form or another.
So lots of progress to report in this field to start the year.
[i] anmarco, L.M., Wheeler, M.A., Gutiérrez-Vázquez, C. et al. Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes. Nature (2021). https://doi.org/10.1038/s41586-020-03116-4.