how our gut health affects our brain

Dr Jess says: When I graduated medical school in 2006 to become a doctor, I had little knowledge about the emerging research on the gut microbiome (the trillions of microorganisms living in our gut). This explosion of evidence came in 2012 and has only grown since then. We are still learning the astonishing number of ways that the gut can influence our health, including its impact on inflammation, our risk of disease, our weight and food cravings and whether we will get or be likely to die from infections. It’s certainly worth thinking about, given the recent pandemic. 

Sadly, medical evidence takes at least 17 years to filter through to standard  medical practice, so it is still rare to hear your GP or consultant talk about the microbiome and the importance of protecting it. 

I agreed to do a talk on the gut-brain connection several years ago and after reading the most recent studies, I was excited to find a wealth of research showing how much of our mood, brain function and even risk of diseases like Parkinson’s’ and Alzheimer’s are linked to gut health. 

This all fits with the knowledge running through traditional medicines, which have emphasised for thousands of years that the gut is the root of disease and that food is our most important medicine. We also have phrases in our language like ‘gut feelings’ and ‘gut instinct,’ which show our innate knowledge that the gut and brain are somehow connected.

I have observed more times than I can count that working on a patient’s nutrition and diet changes their mood and also improves memory, focus, motivation and concentration, whether they are three or 83. The gut-brain axis allows you to take control of your mood and brain symptoms by working on your gut health. 

what is the gut-brain axis?

Simply put, the gut-brain axis is the many ways that our gut communicates with and affects our brain health. Recent research strongly confirms that the gut microbiome (the trillions of microorganisms: bacteria, viruses, protozoa, fungi and parasites in our gut) has a very significant effect on our brain. This connection is by several methods:

  1. Through the interaction between the gut microbiome, the health of the gut wall and the immune system (read more about inflammation here). The release of inflammatory chemicals from the immune cells when the microbiome is imbalanced (dysbiosis) can affect the blood-brain barrier (the barrier protecting the brain) and cause brain inflammation, brain diseases, behavioural changes and mood symptoms.1
  2. In a condition called a leaky gut or intestinal permeability, we see that the leaking of lipopolysaccharide (a toxin produced by an unhealthy microbiome) through the gut wall creates a condition called endotoxemia, which can trigger brain inflammation by stimulating the brain’s ‘immune system’ – the microglial cells. This has been linked to diseases like Alzheimer’s.2 
  3. The vagus nerve is the main nerve connection between the gut and the brain and is their primary method of communication. There is a large nervous system in the gut called the enteric nervous system, which has more nerve cells than our spinal cord. We can measure that the gut is sending much more information to the brain than the other way round. We just don’t know what it is saying (yet)! Recently, we have also learned that abnormal proteins from the gut can move up the vagus nerve and cause diseases like Parkinson’s.3  
  4. Hormones produced by the brain communicate with glands like the adrenal gland (on top of the kidneys) which releases cortisol. This can have a big impact on the gut, increasing intestinal permeability. We call this the HPA axis and it is important in our response to stress (both emotional and physical) and is also activated by inflammation and interacts with the gut microbiome.4 
  5. BDNF (brain-derived neurotrophic factor) is a protein that is produced in the brain that helps new nerve cells to grow. It helps our nerves to form connections, making it very important to our brain function! Research in animals indicates that if they are fed multiple courses of antibiotics, they develop dysbiosis (abnormalities in the gut microbiome) and this results in reduced BDNF expression and a much stronger response to stress.5 
  6. Our gut produces 90% of the happy neurotransmitter serotonin, 50 % of pleasure-seeking dopamine, the sleep hormone melatonin, relaxing GABA and cuddle hormone, dopamine. Whilst we don’t know exactly how this affects the balance of hormones in our brain, we can see that changes in these levels in the gut seem to mirror those in the brain.6

These are only the pathways we have begun to learn about! Evidence and research is relatively new in the exciting and developing field of gut-brain connections. We now need to look at brain diseases and symptoms, mood and psychiatric problems both together and in the context of our whole body, the gut and inflammation. Instead of seeing a neurologist (a brain specialist), psychiatrist (a mood and behaviour specialist), immunologist (an immune system specialist) or gastroenterologist (a gut specialist), maybe we need to have neuropsychoimmunogastroenterologists who consider everything together! All the evidence really shows is how much our gut health, food, immune system and lifestyle can even change our mood, behaviour and brain function. 

the gut brain-axis and disease

We know that conditions like irritable bowel syndrome have a very strong connection with mood disorders like anxiety and depression and we are now linking this to disruption of the gut-brain axis.7 Parkinson’s is now likely linked to an abnormal protein alpha-synuclein, which originates in dysbiosis (abnormality of the gut microbiome) many years before symptoms show and a diagnosis is made.8 Dysbiosis is also now thought to play a major role in dementia and Alzheimer’s, through many of the mechanisms listed above. With dementia a leading cause of death, this should make gut health a priority for us all.9 In the area of mental health, even conditions considered to be difficult to cure, like schizophrenia, may find hope in early microbiome research. 

Animal studies show that faecal transplants (taking poo from one patient and placing it into another’s gut) from patients with schizophrenia put into mice resulted in schizophrenia-like behaviours in the mice.10 Could this mean that healthy faecal transplants may benefit those with schizophrenia? This is a promising area for further study. All research in brain function, mood and the gut-brain axis is in its infancy, but it is very likely from the connections already shown that this field is going to expand dramatically over the next few decades, with targeted microbiome treatments. 

how can we improve our brain function by healing our gut?

Remember that our core gut microbiome is with us for life (each gut microbiome is as unique as a fingerprint). Ours are all formed before the age of three. You get your first microorganisms from your mother as you pass through the birth canal or are breastfed. Even though your core microbiome is developed early in life, the interactions between the bacteria, relationship to other microorganisms (like the virome, the viruses controlling the bacteria) and how the microbiome responds and interacts with the gut can all be improved.

We are also learning that many of the tried-and-tested home remedies and natural gut supports that are hundreds to thousands of years old, like fermented food, plant fibres and herbs, all have positive impacts on the microbiome and gut health. Probiotics have shown so much promise in many behavioural and brain function conditions that they now have the medical name ‘psychobiotics,’ in which research is attempting to isolate specific strains of bacteria to help elevate and improve the mood. 

We know that fibre has a big impact on gut health.The microbiome ferments the fibre in our diets, to create Short Chain Fatty Acids (SCFAs). There are healthy types of SCFA and less healthy types. Butyrate is a very important SCFA that balances the health of the microbiome, is anti-inflammatory, reverses gut damage, heals the blood-brain barrier, helps insulin sensitivity (blood sugar regulation is also extremely important for brain health), mood and contributes to nerve health.11 A diet that is high in fibre and prebiotics can boost butyrate production.  

It is also important to realise that food is the biggest factor in gut health (alongside antibiotics and medications). Pilot studies show that it may only take one meal to change your health. Just a few hours after a high-carbohydrate McDonalds meal, a study showed inflammatory changes that were measurable in the blood.12 People literally became inflamed and sicker because of what they ate. 

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References:

  1. Zhu S, Jiang Y, Xu K, Cui M, Ye W, Zhao G, Jin L, Chen X. The progress of gut microbiome research related to brain disorders. J Neuroinflammation. 2020 Jan 17;17(1):25. doi: 10.1186/s12974-020-1705-z. PMID: 31952509; PMCID: PMC6969442.
  2. Brown GC. The endotoxin hypothesis of neurodegeneration. J Neuroinflammation. 2019 Sep 13;16(1):180. doi: 10.1186/s12974-019-1564-7. PMID: 31519175; PMCID: PMC6744684.
  3. Kim S, Kwon SH, Kam TI, Panicker N, Karuppagounder SS, Lee S, Lee JH, Kim WR, Kook M, Foss CA, Shen C, Lee H, Kulkarni S, Pasricha PJ, Lee G, Pomper MG, Dawson VL, Dawson TM, Ko HS. Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson’s Disease. Neuron. 2019 Aug 21;103(4):627-641.e7. doi: 10.1016/j.neuron.2019.05.035. Epub 2019 Jun 26. PMID: 31255487; PMCID: PMC6706297.
  4. Petra AI, Panagiotidou S, Hatziagelaki E, Stewart JM, Conti P, Theoharides TC. Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation. Clin Ther. 2015 May 1;37(5):984-95. doi: 10.1016/j.clinthera.2015.04.002. PMID: 26046241; PMCID: PMC4458706.
  5. Bistoletti M, Caputi V, Baranzini N, Marchesi N, Filpa V, Marsilio I, Cerantola S, Terova G, Baj A, Grimaldi A, Pascale A, Frigo G, Crema F, Giron MC, Giaroni C. Antibiotic treatment-induced dysbiosis differently affects BDNF and TrkB expression in the brain and in the gut of juvenile mice. PLoS One. 2019 Feb 22;14(2):e0212856. doi: 10.1371/journal.pone.0212856. PMID: 30794676; PMCID: PMC6386304.
  6. Strandwitz P. Neurotransmitter modulation by the gut microbiota. Brain Res. 2018 Aug 15;1693(Pt B):128-133. doi: 10.1016/j.brainres.2018.03.015. PMID: 29903615; PMCID: PMC6005194.
  7. Koloski NA, Jones M, Kalantar J, Weltman M, Zaguirre J, Talley NJ. The brain–gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut. 2012 Sep;61(9):1284-90. doi: 10.1136/gutjnl-2011-300474. Epub 2012 Jan 10. PMID: 22234979.
  8. Caputi V, Giron MC. Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease. Int J Mol Sci. 2018 Jun 6;19(6):1689. doi: 10.3390/ijms19061689. PMID: 29882798; PMCID: PMC6032048.
  9. Kesika P, Suganthy N, Sivamaruthi BS, Chaiyasut C. Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer’s disease. Life Sci. 2021 Jan 1;264:118627. doi: 10.1016/j.lfs.2020.118627. Epub 2020 Oct 22. PMID: 33169684.
  10. Zhu F, Guo R, Wang W, Ju Y, Wang Q, Ma Q, Sun Q, Fan Y, Xie Y, Yang Z, Jie Z, Zhao B, Xiao L, Yang L, Zhang T, Liu B, Guo L, He X, Chen Y, Chen C, Gao C, Xu X, Yang H, Wang J, Dang Y, Madsen L, Brix S, Kristiansen K, Jia H, Ma X. Transplantation of microbiota from drug-free patients with schizophrenia causes schizophrenia-like abnormal behaviors and dysregulated kynurenine metabolism in mice. Mol Psychiatry. 2020 Nov;25(11):2905-2918. doi: 10.1038/s41380-019-0475-4. Epub 2019 Aug 7. PMID: 31391545.
  11. Stilling RM, van de Wouw M, Clarke G, Stanton C, Dinan TG, Cryan JF. The neuropharmacology of butyrate: The bread and butter of the microbiota-gut-brain axis? Neurochem Int. 2016 Oct;99:110-132. doi: 10.1016/j.neuint.2016.06.011. Epub 2016 Jun 23. PMID: 27346602.
  12. Aljada A, Mohanty P, Ghanim H, Abdo T, Tripathy D, Chaudhuri A, Dandona P. Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Am J Clin Nutr. 2004 Apr;79(4):682-90. doi: 10.1093/ajcn/79.4.682. PMID: 15051615.

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