The Immune System of the Brain Stems from the Gut

There were two big biome stories at the end of last week so I’ll use to this week to catch you all up.  Today’s post is about research out of Cambridge University in the UK, in conjunction with our National Institute of Health, which shows just how critical the microbiome is to brain health.[i]  This is a little technical but if I can understand it, so can you!  And it’s definitely worth a read!

As  many of you may remember, as I’ve talked about it many times on this blog, the brain is meant to be protected from the rest of the body by the blood-brain barrier  and the meninges (which are 3 membranes which line the skull and spine – the root of the word meningitis (i.e. inflammation of the meninges)), to prevent anything getting into that crucial organ that shouldn’t be there.  Under normal and healthy circumstances, viruses and bacteria should not be able to make their way into the brain, nor should the immune cells  floating in your blood stream which are attacking pathogens.

What these scientists discovered is that the meninges  actually house their own immune cells called plasma cells, which are positioned right next to large blood vessels (to protect against any invaders being carried in the blood)…and which secrete antibodies to protect the brain.

Now for the slightly technical bit: plasma cells are derived from a kind of immune cell, B cells, which have a unique antibody in their surfaces.  If a germ binds to that antibody, it activates the cell, which in turn, divides to make new cells which can also recognize that antigen.  During the division, the B cell actually creates a mutation (changing 1 amino acid) to change the binding characteristics.  Some of these new “mutated” B cells will better bind to the antigen, and will multiply rapidly – but those less adept at binding (after mutation) will die off.  This ensures that the body is producing the best antibodies for destroying that particular germ.

The antibodies in the blood are normally immunoglobulin G (IgG, which are produced in the spleen and bone marrow).  The scientists were astounded to find that the antibodies in the meninges were IgA, which are the type made in the lining of the gut (and nose and lungs), which protect mucosal surfaces.  They delved deeper, looking at the antibody genes in the B- and plasma-cells of both the gut and in the meninges, and were able to establish that they are indeed related:  those in the meninges of the brain are the offspring of the ones in the gut that had been exposed to particular pathogens, and had replicated.  The defense of the brain starts with the defense system of the gut:  “…meningeal IgA is essential for defending the central nervous system at this vulnerable venous barrier surface.”

Says the lead scientist of this study, Professor Menna Clatworthy, “…even a minor breach of the intestinal barrier will allow bugs to enter the blood stream, with devastating consequences if they’re able to spread into the brain. Seeding the meninges with antibody-producing cells that are selected to recognize gut microbes ensures defense against the most likely invaders.”[ii]  It makes sense, of course:  this system would provide the brain with a way to defend itself from invaders in the gut – and most germs enter through the nose and mouth.

The original work was done in mice and how’s this for incredible:  when the mice were raised germ-free, there were no IgA producing cells in the meninges either.  When the germ-free mice were colonized with probiotics, the IgA plasma cells in the meninges was restored.   When they removed the plasma cells from the meninges of mice, microbes were able to travel from the blood stream into the brain.  They then went on to see if this same system was present in humans and found that indeed, it is.

You have to wonder then what these findings will end up signifying, in terms of diseases that we know start in the gut – like Parkinson’s and autism, to name just a few.  What treatments may eventually evolve from the discovery?  Stay tuned.
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[i] Fitzpatrick, Z et al. Gut-educated IgA plasma cells defend the meningeal venous sinuses. Nature, 2020 DOI: 10.1038/s41586-020-2886-4

[ii] https://www.sciencedaily.com/releases/2020/11/201104121444.htm

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