The Biome/Brain Connection

We know that the brain and immune system are directly connected. We know that 70% or more of that same immune system is located in the lining of the nose and digestive system.  And we know that the digestive system is directly connected to the brain. While we’ve known much of this for decades (except for those lymphatic vessels connecting the brain to the immune system, as per my last post), what has become one of the hottest areas of research now worldwide is the study of how the non-human living organisms of our biome directly affect the brain.

The human body houses about 100 trillion organisms with their own DNA.  It’s astounding that we are only 10% ourselves as those organisms outnumber our cells 10 to 1. I laughed when I read this article a few weeks ago, “Do Microbes Control Our Mood?”[i] which starts off by saying, “If aliens were to examine a human, they would think we were just slavish organisms designed to feed microbes and carry them around.”

So true!  We do indeed serve our co-inhabitants, housing them, feeding them, and if we’re smart, caring for them. The human biome is now recognized as being so integral to health, it is now considered a bodily organ, just like your heart or liver.

How these organisms affect the brain is a hot topic in science research now.  We do know that they communicate with the brain directly. They also have profound indirect effect on the central nervous system.  For example, they help us fight pathogens (thereby, playing an integral part in immunity, which affects the brain) and they make key vitamins that affect the functioning of the central nervous system.

Just this morning, I came across several new papers on this very subject.  One article in particular blew me away:  “The Gut-Brain Axis, BDNF, NMDA and CNS Disorders.”[ii] This came out just this past Friday, and describes how disruption of the gut biome during development negatively affects BDNF (brain derived neurotrophic factor) and the NMDA receptors, which in turn affect synaptic plasticity and cognitive function.  Let’s simplify this:

1. BDNF is a protein and a member of the growth factor family.  That is, it affects nerve growth in the brain.
2. NMDA receptors (often written as NMDAR) are receptors for glutamate. Glutamate is an excitatory neurotransmitter which means it causes neurons to fire.  Abnormalities with this receptor are highly associated with mental disorders including schizophrenia, autism, mood disorders, Huntington’s disease, Alzheimer’s, etc.
3. Gut microbiota modulate BDNF function in the central nervous system by affecting various processes in the body. For example, healthy gut bacteria create short chain fatty acids, which are highly anti-inflammatory and which cross the blood-brain barrier, affecting various brain chemicals.
4. In the absence of normal gut bacteria (i.e. a baby that has been given antibiotics early in life, while the brain is still developing), BDNF levels are lowered, which leads to abnormalities in the development of the NMDAR, which leads, in turn, to excessive glutamatergic output.
5. Excessive glutamatergic output the brain leads to extreme brain hyper-reactivity. (Many anti-seizure medications, in fact, reduce brain glutamate to calm the brain down.)

“In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits.”

 So, here we have just 1 potential mechanism whereby altering gut bacteria may affect brain development and cognition.  Within minutes of finding this article, I found this one, published in September, “Cognitive Function and the Microbiome,”[iii] which states:

“Cognition was originally thought to be exclusively regulated by the central nervous system, with long-term potentiation and neurogenesis contributing to the creation and storage of memories, but now other systems, including, for example, the immune system and the intestinal microbiome may also be involved.”

And then I found this one, also just published, “The Central Nervous System and the Gut Microbiome”:[iv]

“…emerging data suggest communication between the gut and the brain in anxiety, depression, cognition, and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain barrier, myelination, neurogenesis, and microglia maturation and also modulates many aspects of animal behavior.”

I genuinely believe we are living through a medical revolution, as historically important as when “germs” were first discovered in the 1850s.  I believe we will learn to fix “broken” microbiomes (more on this in future posts), and with all my heart, I hope we learn to fix the CNS damage such unhealthy biomes may have caused.

 

 

[i] https://www.sciencedaily.com/releases/2016/10/161020114611.htm

[ii] Maqsood, R. & Stone, T.W. Neurochem Res (2016) 41: 2819. doi:10.1007/s11064-016-2039-1

[iii] Gareau, M.G. (2016). Chapter Eleven – Cognitive Function and the Microbiome. International Review of Neurobiology. Volume 131, 227-246.

[iv] Sharon, G., Sampson, T.R., Geschwind, D.H., Mazmanian, S.K. (2016). The Central Nervous Ssytem and the Gut Microbiome. Cell 2016  Nov 3;167(4):915-932. doi: 10.1016/j.cell.2016.10.027.