ATP Project Podcast 108

Gut versus Brain

The enteric nervous system (ENS), along with the sympathetic and parasympathetic nervous systems, make-up the autonomic nervous system.

The human ENS contains more than 100 million neurons; which is more than the peripheral nerves of the sympathetic and parasympathetic nervous system combined, about the same number of nerves as in the spinal cord and of which dwarf the number of efferent fibres that reach the gut in the vagus nerves.[1]

Balance between the sympathetic nervous system (stress and survival) and the parasympathetic nervous system (rest and digest) do influence digestion by manipulating your body’s priorities depending on whether your brain thinks you need to fight or escape a stress or if you are allowed to relax and eat. But the ENS controls the digestive process itself.

Sympathetic stimulation causes inhibition of gastrointestinal secretion and motor activity, and contraction of gastrointestinal sphincters and blood vessels.

Parasympathetic stimuli typically stimulate digestive activities.

Enteric nervous system

ENS is described as second brain but I don’t know about that. It might get a lot of the first say as it is the first line of defence and if you consider that 90% of the gut-brain nerve fibres are sending stuff to the brain and only 10% are fibres sending instructions form the brain to the gut.

ENS secretes the full array of neurotransmitters; GABA, noradrenaline (norepinephrine), serotonin, acetylcholine and dopamine. As well as other chemical messengers and peptides like GLP-1, neuropeptide Y, ghrelin, Leptin etc.

In the brain, these neurotransmitters induce mood changes. In our gut, they control mucous and movement and blood flow and control how the mucous membrane and muscle of the bowel work together.

Then they are sent to the brain to work as well. Most of the neurotransmitters in the brain are made in the gut ENS.

Gut v Brain v Immune System

The innate immune system throws in more curve balls when trying to decide who is in actual control over your brain and gut. Cytokines are chemical messengers originally linked to immune cells but we now know that these chemicals are also released from nerve cells in the enteric nervous system as well as other peripheral and central nervous systems. They instantly induce a cascade of events that include physical and mental symptoms of stress and pain and interact directly with other neurotransmitters.

Allergies and the ENS

Allergies drive up a chemical called histamine in the body. Histamine is the nasty chemical that causes your nose to run and cause mucus to form. Anti-histamines are often taken as a response to this annoying effect. Exposure of the ENS to histamine, either by exogenous application in vitro or by release from sensitised mast cells in response to allergens (for example, food proteins or infectious organisms), alters neurotransmitter balance and function.

Basically, allergens stimulate the release of histamine, which screws with numerous neurotransmitters, which means the neurons are unable to communicate effectively with each other, leaving the individual with a huge array of neurological symptoms (depression, anxiety, fatigue etc). The problem with this is that if someone is diagnosed with anxiety and treating with an anti-anxiety drug, the cause may never be addressed, leaving with the sufferer on potentially incorrect medications and the thought that they are ‘messed up in the head’ when they may have a simple dust, pollen or wheat allergy.

Gut Flora

The human genome project has shown just how tiny the human gene pool is compared to others in nature for example the human gene pool has 26,000 units compared to rice that has 46,000 functioning genes that have evolved over time. How can such a complex creature as a human have so much less than rice? It is possible that it is because we have a symbiotic relationship with other microbes that are also a part of us and we get access to their gene pool of functions. There are 10x as many bugs in our guts than whole cells of our whole body after all.  A hundred trillion bacteria in one adult human contains 4 million bacterial genes, with more than 95% of that isolated to our large intestine.

This gut flora interacts directly with the ENS. We are still learning just how powerfully it interacts.

Gut Bugs make Neurotransmitters

We will learn more of what they make and do but for starters:

Lactobacillus – acetylcholine and GABA

Bifidobacterium – GABA

E.Coli – noradrenalin (norepinephrine), serotonin, dopamine

Streptococcus – serotonin

Bacillus – noradrenalin, dopamine

Gut bugs also feed on neurotransmitters for example noradrenalin from stress feeds E.Coli and clostridia and reduces other bacteroides.

So, which comes first the stress leading to infection or the infection leading to stress?

Answer may be different each time but needs to be investigated properly.

Many Brain Disorders may actually be gut Disorders and need further investigation;

But there will be so many more…

  • Parkinson’s disease.
  • Autistic spectrum disorder.
  • ADD, ADHD.
  • Some forms of depression.
  • Some forms of anxiety.
  • Alzheimer’s disease.

There are Multiple different ways the ENS can create Chronic Disease

  • Excitatory neurotransmitters like glutamate in ENS and then CNS from your diet and gut flora.
  • Immune and inflammation activation and subsequent tissue damage.
  • Apoptotic (self-destruct mechanism in cells) triggers.
  • Neurotransmitter dysregulation.
  • Leaky gut wall and blood brain barrier.

 

Recommended reading from the podcast

Galland L.The gut microbiome and the brain. J Med Food. 2014 Dec;17(12):1261-72. doi: 10.1089/jmf.2014.7000.

Ochoa-Cortes F1Turco FLinan-Rico ASoghomonyan SWhitaker EWehner SCuomo RChristofi FL. Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases. Inflamm Bowel Dis. 2016 Feb;22(2):433-49.

Fichter M1Klotz MHirschberg DLWaldura BSchofer OEhnert SSchwarz LKGinneken CVSchäfer KH. Breast milk contains relevant neurotrophic factors and cytokines for enteric nervous system development. Mol Nutr Food Res. 2011 Oct;55(10):1592-6. doi: 10.1002/mnfr.201100124. Epub 2011 Aug 2.

Perez GG1Schneider LCButtow NC. Ginkgo biloba (EGb 761) extract: effects on the myenteric plexus of the large intestine in Wistar rats. Dig Dis Sci. 2009 Feb;54(2):232-7. doi: 10.1007/s10620-008-0338-3. Epub 2008 Jul 9.

Yin Y1Zhong L1Wang JW1Zhao XY1Zhao WJ1Kuang HXTong Xie Yao Fang relieves irritable bowel syndrome in rats via mechanisms involving regulation of 5-hydroxytryptamine and substance P. 2015 Apr 21;21(15):4536-46. doi: 10.3748/wjg.v21.i15.4536.

Yao CK1Muir JG1Gibson PR1. Review article: insights into colonic protein fermentation, its modulation and potential health implications. 2016 Jan;43(2):181-96. doi: 10.1111/apt.13456. Epub 2015 Nov 2

Ochoa M1Lallès JPMalbert CHVal-Laillet D. Dietary sugars: their detection by the gut-brain axis and their peripheral and central effects in health and diseases. 2015 Feb;54(1):1-24. doi: 10.1007/s00394-014-0776-y. Epub 2014 Oct 9.

Hansen MB1Witte AB. The role of serotonin in intestinal luminal sensing and secretion. 008 Aug;193(4):311-23. doi: 10.1111/j.1748-1716.2008.01870.x. Epub 2008 Jun 28.

Nat Rev Gastroenterol Hepatol. Serotonin signalling in the gut–functions, dysfunctions and therapeutic targets. 2013 Aug;10(8):473-86. doi: 10.1038/nrgastro.2013.105. Epub 2013 Jun 25.

Savidge TC1Newman PPothoulakis CRuhl ANeunlist MBourreille AHurst RSofroniew MV. Enteric glia regulate intestinal barrier function and inflammation via release of S-nitrosoglutathione. 2007 Apr;132(4):1344-58. Epub 2007 Feb 1.

Kirchgessner AL1Liu MTAlcantara F. Excitotoxicity in the enteric nervous system. 997 Nov 15;17(22):8804-16.

Böttner M1Barrenschee MHellwig IHarde JEgberts JHBecker TZorenkov DWedel T. The enteric serotonergic system is altered in patients with diverticular disease. 2013 Dec;62(12):1753-62. doi: 10.1136/gutjnl-2012-302660. Epub 2012 Nov 10.

Yu Y1Wu SLi JWang RXie XYu XPan JXu YZheng L. The effect of curcumin on the brain-gut axis in rat model of irritable bowel syndrome: involvement of 5-HT-dependent signaling. . 2015 Feb;30(1):47-55. doi: 10.1007/s11011-014-9554-z. Epub 2014 May 8.

Gershon MD1. Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense. 2012;123:268-80; discussion 280.

Forsythe P1,2,3Kunze W4,5Bienenstock J6,5. Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis? 2016 Apr 19;14:58. doi: 10.1186/s12916-016-0604-8.

Burapan S1Kim M1Han J1. Curcuminoid Demethylation as an Alternative Metabolism by Human Intestinal Microbiota. 2017 Apr 26;65(16):3305-3310. doi: 10.1021/acs.jafc.7b00943. Epub 2017 Apr 14.

Berg CJ1Kaunitz JD2. Gut chemosensing: implications for disease pathogenesis. 2016 Sep 30;5:2424. eCollection 2016.

Mazzoli R1Pessione E1. The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling. 2016 Nov 30;7:1934. eCollection 2016.

Frantz DJ1. Neurologic complications of bariatric surgery: involvement of central, peripheral, and enteric nervous systems. 2012 Aug;14(4):367-72. doi: 10.1007/s11894-012-0271-7.

[1] Furness, JB. The Enteric Nervous System. Blackwell Publishing; 2006.