Growing evidence for anatomical Mind-Gut link

By Eva Istsenko

If your ‘gut is telling you’ that something is up, or you’ve ever felt ‘butterflies’ when you look at that special someone, that is because of bidirectional Brain- Gut connection. Two thin layers of over 100 million nerve cells line the gastrointestinal tract from oesophagus to rectum and are called the enteric nervous system (ENS) or sometimes ‘our second brain’ (hopkinsmedicine.org, 2019). 

It was conventionally thought that gastrointestinal branches of the vagus nerve were the centre of the Brain-Gut axis (Rege, 2019), mainly responsible for the feeling of hunger or satisfaction after a meal. More recent studies show that the function of the ENS is much wider than that, playing a significant role in various neuropsychological processes, like anxiety, depression and even autism (Fan, 2019). Until recently the Brain-Gut circuit remained unmapped, due to difficulty in isolating specific vagal organ afferents. However, using a combinatorial viral detection approach, a modified light sensitive rabies virus was injected into wild-type mice and, using laser stimulation, sensory neurons in the upper gut were excited. Rabies virus has the ability to ‘jump’ from one synapse to another and travel to the brain, so its movement was tracked and mapped (Han, 2018). The study showed direct anatomical link between the gut and the brain.

The results demonstrate a previously unproven direct relationship between the ENS and CNS (central nervous system) and may mean new treatment opportunities. About 20% of people struggle with depression during their lifetime. Depressed patients may suffer not only from a mental disorder but from immune system dysfunction and hormonal imbalance. While most common treatments include antidepressants or cognitive therapy that work by increasing serotonin levels, more recent theories believe that gut health plays a big component in brain conditions.  Our gut contains the biggest variety of microorganisms in our body- bacteria, viruses, fungi and so on, called microbiota. Depressed patients have less rich and active microbiota than a healthy person. This leads to disturbed function of the HPA (hypothalamic–pituitary–adrenal) axis and excess production of the stress hormone cortisol (Greenberg, 2018), as well as inconsistent levels of the neurotransmitter serotonin, proven to be a mood-booster. 

Another gastrointestinal disease, overlapping mind and gut, is IBS (irritable bowel syndrome), affecting 10-15% of western population. IBS is characterized by constipation, diarrhoea, abdominal pain and may also lead to intestinal cysts and more. IBS patients also suffer from hypersensitivity and lower pain tolerance. Using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) it was determined that IBS subjects have disturbed bidirectional message relay between the brain and gut. There are different mechanisms of how the brain-gut axis may be affected- cortisol release and processing, stress response, inflammation and more, depending on the IBS subtype (Coss-Adame and Rao, 2014). All of this switched the believe that mental illnesses are the consequence of IBS, but rather shows they may be the cause. 

Finally, in the recent years there has been increasing speculation of relationship between gastrointestinal (GI) disorders and autism spectrum disorder (ASD) which includes several developmental disorders. Two main factors contribute to its occurrence- genetics and environment. For instance, malfunctioning serotonin transporters (SERT) lead to lower motility, decreasing intestinal permeability, leading to smaller number of neurons in submucosal neural networks in ENS. It is also believed that ‘Western’ habits, like excessive antibiotics use and hygiene, high-fat and high-sugar diets, ethanol use and C section birth could be the cause for microbiota disbalance. It is believed that ‘healthy’ microbiota is 70% Gram negative bacteria and 30% Gram positive, while ASD children have a higher percentage of G negative bacteria. This results in higher number of lipopolysaccharides (LPS) and pro-inflammatory cytokines, which in order leads to ‘leaky’ gut, which is damage of gastrointestinal and blood brain barriers, allowing toxins and waist products to reach the bloodstream (Lasheras, 2020). Although it is still unclear how exactly gut microbiota affects the development of ASD brain, because of heterogeneity of conducted studies; many agree on distinct microbial pattern in ASD patients.  

So far, the best way to target poor variety of gut microorganisms is by pre- and probiotics. Prebiotics are undigestible oligo- and polysaccharides—fructooligosaccharides or galactooligosaccharides (GOS), which promote bacterial growth and/or activity, often helping increase in bifidobacteria and inhibition of harmful types like Clostridia or Coliform. Probiotics are live or weakened microorganisms and the type of given probiotic depends on individual concern. Natural sources include fermented products like yogurt or pickles. Another supplement that shows to be effective is omega-3, which can positively affect microbiota by increasing anti-inflammatory compound content, such as fatty acids (Menees and Chey, 2018). Omega-3 can be naturally found in fatty fish, for example salmon or sardines. Other treatment suggestions include improving overall lifestyle with a cleaner diet, reduced stress and sufficient exercise. 

The gut- brain axis research is a promising field opening up a large number of opportunities for further investigations in neurology, gastroenterology and microbiology. But it is certain that there is a strong link between our gut condition and the brain, which can lead to innovative ways to treat one through the other. It is a challenging area of research since the axis can be influenced by variety of factors like age, ethnicity, diets, inheritance, etc. so collecting sufficient homogenous sample size has been a struggle, most studies so far were conducted on animals. However, we can say with certainty that our mental health is as important, as our physical health. 

References:

Fan, S. (2019). 5 Discoveries That Made 2018 a Huge Year for Neuroscience. [online] Singularity Hub. Available at: https://singularityhub.com/2019/01/17/5-discoveries-that-made-2018-a-huge-year-for-neuroscience/ [Accessed 9 Sep. 2020]. 

Greenberg, M. (2018). Feeling Depressed? Gut-Brain Dysfunction May Be to Blame. [online] Psychology Today. Available at: https://www.psychologytoday.com/us/blog/the-mindful-self-express/201812/feeling-depressed-gut-brain-dysfunction-may-be-blame [Accessed 9 Sep. 2020]. 

Han, W. (2018). A Neural Circuit for Gut-Induced Reward. [online] cell.com. Available at: https://www.cell.com/cell/fulltext/S0092-8674(18)31110-3?utm_source=STAT+Newsletters&utm_campaign=ec49afc536-MR_COPY_08&utm_medium=email&utm_term=0_8cab1d7961-ec49afc536-149692869#secsectitle0030 [Accessed 9 Sep. 2020]. 

hopkinsmedicine.org. (2019). The Brain-Gut Connection. [online] Available at: https://www.hopkinsmedicine.org/health/wellness-and-prevention/the-brain-gut-connection [Accessed 9 Sep. 2020]. 

Rege, S. (2019). The Simplified Guide to the Gut Brain Axis – How the Gut Talks to the Brain. [online] Psych Scene Hub. Available at: https://psychscenehub.com/psychinsights/the-simplified-guide-to-the-gut-brain-axis/ [Accessed 9 Sep. 2020]. 

Coss-Adame, E. and Rao, S.S.C. (2014). Brain and Gut Interactions in Irritable Bowel Syndrome: New Paradigms and New Understandings. Current Gastroenterology Reports, [online] 16(4). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4083372/ [Accessed 9 Sep. 2020]. 

Lasheras, I. (2020). Microbiota and gut-brain axis dysfunction in autism spectrum disorder: Evidence for functional gastrointestinal disorders. Asian Journal of Psychiatry, [online] 47, p.101874. Available at: https://www.sciencedirect.com/science/article/pii/S1876201819307476#bib0320 [Accessed 9 Sep. 2020]. 

Menees, S. and Chey, W. (2018). The gut microbiome and irritable bowel syndrome. F1000Research, [online] 7, p.1029. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039952/ [Accessed 9 Sep. 2020]. 

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