What is the Gut-Brain Axis?
This week we explain a much quoted term in gut health - the gut-brain axis. We note that it can help explain the many varied origins of gut conditions like IBS.
Our explanation uses lots of technical terms and acronyms - human bodies are beautifully complex things. If human biology is not your thing, we recommend you jump ahead to the suggestions about how you can exploit the axis to improve your gut health, and perhaps your cognitive and emotional health too.
Ok, let’s jump in.
Gut to brain:
Communication from the gut to the brain is less well understood. However, sensory neurons in the gut do detect changes in the environment (e.g., nutrient levels, gut motility) and relay this information back to the brain.
Endocrine System Communication:
Brain to gut:
Something called the HPA axis is a key player in hormonal regulation of gut function – it also links through to the parasympathetic nervous system. The HPA connects together the hypothalamus, pituitary gland and the adrenal cortex. It responds to either emotional or environmental stress, detected by the limbic (primitive) brain or immunological stress signalled through pro-inflammatory cytokines.
Stress activates the HPA axis leading to widespread effects in the gut. Here’s how it works:
Hypothalamus: Located in the brain, the hypothalamus contains neuroendocrine neurons that synthesize and secrete corticotropin-releasing hormone (CRH).
Pituitary Gland: CRH and another hormone called vasopressin stimulate the anterior lobe of the pituitary gland to release adrenocorticotropic hormone (ACTH).
Adrenal Cortex: ACTH travels through the bloodstream to the adrenal cortex (located on top of the kidneys). There, it stimulates the production of glucocorticoid hormones, primarily cortisol in humans.
Cortisol: This stress hormone has widespread effects on various tissues, including the gut.
It modulates gut immune responses, influencing inflammation and tissue repair.
It influences the integrity of the gut barrier which prevents harmful substances from entering the blood.
Cortisol affects the gut microbiota composition.
It influences gut motilty, nutrient absorption and metabolism.
Cortisol also acts back on the hypothalamus and pituitary, suppressing CRH and ACTH production in a negative feedback loop.
It’s unsurpring then that dysregulation of the HPA axis due to chronic stress can lead to gut disorders. This is a possible cause of IBS.
Gut to brain:
Hormones produced in the gut (e.g., leptin, ghrelin, glucagon-like peptide-1) influence appetite, metabolism, and mood. If you, like me get hangry around 11:00am, blame your hormones (and have more protein and fibre at breakfast).
These hormones can cross the blood-brain barrier and directly affect brain regions involved in emotion and thinking.
Immune System Communication:
Immune cells in the gut interact with the CNS through cytokines, chemokines, and other signalling molecules. Inflammation in the gut can affect brain function and vice versa (see above).
The Gut Microbiome: A Key Player
The concept of the gut-brain axis has recently been extended to include the gut microbiome. The gut microbiome is composed of trillions of microorganisms. There is good evidence that it can influence gut health, and there are growing indications that it may also influence the gut-brain axis.
Research on the gut microbiome has made great progress in recent years as the cost of sequencing and identifying the different microbres has got easier. However, to some extent, this area of research it is still in it’s infancy. Most study has focused on the species that exit the gut in the poop, rather than the species that are remain in the mucous layer lining the gut , and arguably might be expected to have have more effects.
It is not really clear exactly what constitutes a ‘healthy microbiome’. This may differ for different individuals. It appears that to some degree there is redundancy built in the system, so that multiple genera of microbes can take on the key roles of producing positive metabolites in different people. Generally though, a few patterns appear to be correlated with good health:
a higher diversity of different genera
a good balance of Bacteroidetes compared to Firmicutes bacteria (increased F/B ratio is associated with obesity, but decreased F/B is associated with inflammatory bowel disease).
an abundance of the groups that convert prebiotic fibre into short chain fatty acids (SCFAs) such as Bifidobacterium and Lactobacillus. SCFAs are fuel for colon cells and help maintain a healthy gut barrier. They also stimulate serotonin production in the gut that modulates motility.
a low abundance of so-called “pro-inflammatory” bacteria, potential pathogens, and those that produce bacterial toxins such as lipopolysaccharide (LPS).
Gut dysbiosis, an imbalance in microbial composition or movement away from these patterns, has been linked to gut symptoms, dysfunction in the gut-brain axis, and possibly neurodegeneration. Dysbyosis after an infection can cause post-infection IBS in some people.
Generally, it appears that the microbes interact locally with intestinal cells and the enteric nervous system, and may also interact directly with brain through neuroendocrine and metabolic pathways.
Mechanisms:
Microbes produce metabolites (e.g., short-chain fatty acids) that affect many parts of the body including the brain. For example they downregulate the synthesis of the hunger-suppressing hormones.
Other metabolites, such as the bacterial toxin lipopolysaccharide (LPS) can have negative effects, especially if they cross through a leaky gut-barrier.
They modulate the immune system, influencing brain health.
The gut-brain-microbiome axis may be a potential therapeutic target
However, much of the evidence for these effects comes from animal studies, that are quite extreme in nature…and it is unclear to what extent they reflect the natural state of affairs in humans. The findings from these studies include:
Germ-free mice (raised without gut microbes) exhibit altered gut motility and behaviour, memory and brain function
Transplanting specific gut microbes into germ-free mice or providing probiotics can restore normal behavior and memory if done early enough.
Microbial metabolites influence neurotransmitter production.
Alternatively, research data comes from association studies in humans, but causality is not always clear in these types of studies. For example, people with IBS tend to have different signature gut microbiome pattern, but it is unclear if the microbiome changes are due to the changed gut motility patterns that occur in IBS, or the cause via effects on the gut-brain axis.
Similarly, it is perhaps too early to be confident that we can use the gut-brain-microbiome axis to treat neurodegnertive diseases such as Parkinson’s, but new research may get us there. We were excited to read recently that a team at Queensland University of Technology have received funding to work on this very problem. They hope to be able to identify so-called "healthy bugs" that may disappear in people with Parkinson's and then find ways to to develop drugs to target the microbes. They will also engineer bacteria and test their potential to slow or stop Parkinson's progression by altering the gut ecosystem. Exciting stuff!
What can you do right now?
Try techniques like deep breathing to stimulate the parasympathetic system. Breathing exercises that extend the out breath relative to the in breath are best. Slow controlled breathing with long exhales moves the nervous system away from the fight-or-flight mode and towards rest-and-digest. Try the 4-7-8 breathing technique that involves breathing in for 4 seconds, holding the breath for 7 seconds, and exhaling for 8 seconds.
Yoga, meditation, and progressive muscle relaxation can also stimulate the parasympathetic system, as well as the colour blue and being out in nature. A walk by a river or ocean is perfect to re-set your parasympathetic system.
Consume plenty of prebiotic fibre to feed the beneficial bacteria that can influence your gut-brain axis. Prebiotic fibre is converted into SCFAs that feed colon cells and has a whole raft of positive effects through the body including the liver and brain.
A Mediterranean diet rich in fish, legumes, olive oil and fruit and vegetables is also linked to a well balanced microbiome. Reduce your intake of refined sugar and fats that lead to dysbiosis, a leaky gut and increased inflammation.
A disordered gut-brain axis leads to visceral hypersenitivity (making bloating extra painful). The low FODMAP diet reduces fermentation of carbohydrates in the gut so that you experience less gas, bloating and discomfort.
These changes are all likely to improve your gut health, and may also have long term positive effects on mood and brain health too.
References:
Bicknell, B., Liebert, A., Borody, T., Herkes, G., McLachlan, C., & Kiat, H. (2023). Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome. International journal of molecular sciences, 24(11), 9577. https://doi.org/10.3390/ijms24119577
Margolis, K. G., Cryan, J. F., & Mayer, E. A. (2021). The Microbiota-Gut-Brain Axis: From Motility to Mood. Gastroenterology, 160(5), 1486–1501. https://doi.org/10.1053/j.gastro.2020.10.066
Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28(2), 203–209. link