So, for example, when I was young, we were taught in medical school that there was such a thing as an ulcerative-colitis personality. People with ulcerative colitis [a chronic disease of the large intestine] have hard-driving, Type A personalities; they are obsessive compulsives, perfectionists, and neurotic. And those with Crohn’s disease are very nervous and high-tension people. We now know that these are autoimmune diseases, like rheumatoid arthritis and lupus.
It’s not that the brain is doing something bad to the gut. We think bad thoughts put holes in the colon. What is happening is that the holes in the colon make people think bad thoughts. The personality disorders go away when you take the damn colon out and leave ulcerative colitis.
BW: When you spoke of the two systems and two neurotransmitters earlier, which transmitters were they?
MG: Acetylcholine, and what they thought was epinephrine turned out to be norepinephrine (adrenaline and noradrenaline). Acetylcholine is one of the most important neurotransmitters in the body. It’s the one that makes your skeletal muscles work. The nerve-to-skeletal-muscle junction and 100% of the muscle is turned on by acetylcholine. So, that’s critical. Nerve gas blocks the ability of the body to turn off acetylcholine. And it’s deadly, because if you can’t turn it off, your muscles just become flaccid and can’t work.
BW: Can you talk about your work with serotonin?
MG: Serotonin was first known to be a neurotransmitter in the brain. While working with Edith Bülbring, I became aware of the fact that 95% of the body’s serotonin is actually found in the gut, not the brain. So, the brain is just a small afterthought in terms of the amount of serotonin that is present in the body.
Brain and gut serotonin are completely different because the blood-brain barrier does not let serotonin go through it. So, all the serotonin that’s in the brain is made there, and all the serotonin the gut puts out into the rest of the body (including the 2 to 3% of it found in the blood) is essentially made in the gut.
Now, the serotonin that’s in the brain seems to be involved in everything that makes life worthwhile. For example, it’s important for happiness and in fighting depression. It’s involved in sex, eating, sleeping, and dreaming. I mean, it’s wonderful stuff, but, quantitatively speaking, the gut is where it’s at.
I began looking at what it does there. As it turns out, it’s involved in many, many different kids of things. It’s what I’m now calling a polyfunctioning molecule. The gut has serotonin that is part of the sensing system, and so, when bacteria — and there are plenty of those in your gut — begin to invade, an anti-inflammatory response, which is anti-bacterial, is set up. This is independent of the brain.
However, the inflammation in the gut, which serves to prevent invasion, is potentially damaging to the gut, so the nerve cells in the gut can be collateral damage. But serotonin in the nervous system has a completely different role. Instead of promoting inflammation, it blocks it. And inside the gut, it protects the neurons from inflammation, so if any get killed, it helps make new ones from stem cells. So serotonin acts like the sword and shield of the gut. It also has a number of other functions.
BW: What would happen if serotonin wouldn’t do that?
MG: Animals that have reduced serotonin signaling, turns out, have bacterial overgrowth. It comes charging up out of the colon and the big and small intestine, and, if you monitor that, you see this constant bacterial invasion. They don’t fend off bacteria very well.
But what’s very interesting is that lots of diseases of the brain also affect the gut. For example, Alzheimer’s and Parkinson’s cause problems in the gut. In fact, in Parkinson’s patients, their guts are affected long before they have motor symptoms and can cause them to become profoundly constipated. Similarly, the gut doesn’t function very well in individuals with an autistic spectrum disorders.
There are only a few tens of thousands of serotonin nerve cells in the brain, but they project to many regions of the brain and are necessary for modulating brain function.
BW: How do you study the effects of serotonin in the body?
MG: We now have lots of tools to study it that are very novel. For example, we can look at mice that have no serotonin in the lining of the gut, mice that have no serotonin in the nervous system but have plenty of it in the lining of the gut, and mice that have no serotonin at all — the latter are very unhappy animals. If you eliminate all of the serotonin in the body, you will survive, but you wouldn’t survive very well.
This article is updated from its initial publication in Brain World Magazine’s print edition.
