The complex world of the enteric nervous system and its relationship with the microbiome.
Introduction
Have you ever had a ‘gut feeling’ about something, or experienced the sensation of ‘butterflies in your stomach’ when you felt nervous or excited? Well, as it turns out, the gut has long been considered the seat of emotion, and these common expressions are rooted in biology.
Put simply, the gut-brain axis is the two-way connection and communication that takes place between the gut and the brain, linking the central nervous system (CNS) to the enteric nervous system (ENS).
There are other systems involved, but we’ll focus on the CNS and ENS in this tile.
We’ve known about the gut-brain axis for a long time, but as interest in the microbiota has soared, we’ve come to learn that the microbes in our gut are intimately involved in this conversation between brain and gut. For this reason, we’ll refer to the two-way link as the microbiota-gut-brain axis (MGBA).
Enteric nervous system
The enteric nervous system (ENS) is made up of a vast network of neurons, or nerve cells. The exact number is disputed but estimates range from 100 million to between 200 and 600 million – the same number of neurons found in the human spinal cord. No wonder, then, that the ENS is referred to as the “second brain”!
The neurons in the ENS talk to the microbes in the gut and send signals to the brain via a network of nerve endings in the intestinal wall – allowing the ENS to talk to the CNS without having to cross the blood-brain barrier. The blood-brain barrier protects the central nervous system from toxins and pathogens in the blood. Most of these signals are sent via the vagus nerve, which is one of several pathways of communication between these two systems.
Vagus nerve, part 1
The vagus nerve is the longest nerve in the human body, reaching all the way from the brainstem to the large intestine. It provides a physical link between gut and brain and allows these two organs to talk to each other.
Vagus is a Latin word meaning ‘wandering’. Although its name is singular, it’s actually a pair of nerves. The right vagus nerve travels down the right side of your body, while the left vagus nerve travels down the left side of your body, like a divided highway, relaying traffic in the form of signals through your neurons, from the brain to the gut, and vice versa.
Vagus nerve, part 2
The vagus nerve is an essential part of the gut-brain axis and is involved in controlling inflammation, regulating food intake and satiety, and maintaining energy homeostasis in the gut. Research also seems to suggest a poorly functioning vagus nerve could lead to psychiatric disorders, obesity, and other diseases brought on by stress and inflammation. In fact, vagal nerve stimulation – where electrical impulses are sent to the brain via the vagus nerve – is now a well-known treatment for depression, particularly in cases that don’t improve with therapy and medication.
The conversation that goes on between brain and gut happens both ways, but most of the signals – around 80% – are sent from the gut to the brain. Several pre-clinical studies have shown this ‘bottom-up’ signaling can affect cognitive development and mood.
This is important for our understanding of the role of the microbiota in health and disease. We used to think that gastrointestinal disorders like irritable bowel syndrome caused depression, but we now know that signals for depression are mostly sent from the gut to the brain.
Neurotransmitters
Neurotransmitters are chemical messengers that play a key role in the microbiota-gut-brain axis. Serotonin, produced by both neurons in the brain and enterochromaffin cells in the gut, has been linked to depression and anxiety disorders. Dopamine is another neurotransmitter involved in this system; prebiotic fibers can modulate dopamine release from enteroendocrine cells which could potentially improve cognitive function. Acetylcholine is also important for cognition and memory formation; stimulating the vagus nerve may increase levels of acetylcholine, leading to improved performance on cognitive tasks.
GABA, short for gamma-aminobutyric acid, is a neurotransmitter believed to play a role in behavior, cognition and the body’s response to stress, fear, and anxiety. GABA is produced by some Lactobacilli and specific strains of Bifidobacterium. Low GABA levels are associated with a range of mental health issues, including depression and schizophrenia.
Metabolites
The microbiota-gut-brain axis is not only involved in the production of neurotransmitters, but also in the production of metabolites. Metabolites are small molecules produced by bacteria that can have a wide range of effects on our health. For example, short chain fatty acids (SCFAs) such as acetate and propionate are produced when dietary fiber is fermented by gut microbes. SCFAs can reduce inflammation, improve insulin sensitivity and even act as appetite suppressants – all beneficial for maintaining good health. Another important metabolite is indolepropionic acid (IPA), which has been linked to improved cognitive performance and reduced risk of neurodegenerative diseases like Alzheimer’s disease.
In addition to these metabolic benefits, certain bacterial species produce vitamins essential for human nutrition such as vitamin K2 and B12. Vitamin K2 helps regulate calcium levels in the body while B12 plays an important role in energy metabolism and red blood cell formation. These vitamins cannot be synthesized by humans so it’s essential that we get them from our diet or through supplementation with probiotics containing these bacteria strains. By understanding how metabolites interact with our bodies we can gain insight into how they affect our overall wellbeing – both physical and mental!
Gut microbes and mental health
The community of microbes in our gut has been shown to play a role in the onset of mental illness. Several studies have linked the presence of an overgrowth of the Toxoplasma gondii parasite to obsessive compulsive disorder, or OCD. A recent study on mice revealed that a metabolite called 4EPS produced by bacteria in the gut can travel to the brain and alter the function of brain cells, leading to increased anxiety.
Neurological research suggests that microbiota also play a role in neurodegenerative diseases. This lends support to the idea that an ageing gut microbiota could be linked to immune and neuron dysfunction in Alzheimer’s and Parkinson’s disease.
As is typical with dysbiosis, these pathogens are able to proliferate, destroy the good bacteria and colonize the guts of patients whose microbiotas have been dysregulated by illness or antibiotics.
