In previous articles about the microbiome we explored the microbiome and its host connection with digestion and the Immune system. We have simply ‘wetted the appetite’ since these subjects are highly complex and there are volumes of research and many books that are out there covering these topics but our goal is to present our articles in ‘Layman’s terms’ and not ‘baffle’ you with science.
For our bodies to work well and for us to feel well the body as a complex carbon life form must function in equilibrium and be homeostatically balanced; the body prefers this state and it prefers little change like any functional system..once it’s working, don’t try to fix it. However, if the body does ‘Gets out of kilter’ then you have no choice but to fix it, unless you want to suffer, trust me, and millions of us when we say it’s not worth being in the land of the miserable for the sake of a daily crispy cream donut.
I have stated this before but balance is crucial within the host and between the host and its microbial neighbors. A plethora of exogenous and endogenous factors exist just waiting to upset the balance. Conventional medicine is very capable of identifying and aptly naming the enormous number of physiological and psychological conditions that can ignite if the body becomes unbalanced physically, chemically and psychologically. However, when they occur and you ask the obvious ‘Why?’ The reply from your physician generally is “We don’t know why this happens…it could be genetic..old age..susceptibility of your body”…I know… Why don’t I ask Mr Bun the Baker or even the Candlestick maker or even the Mad Hatter, they might be able to help.
What is wrong with examining the patient as a whole entity ( just like they used to in the old days ) and ask the question WHY do you have these symptoms? What has become ‘unhinged’ or unbalanced instead of spending 15 minutes for the physician to figure out what drug to prescribe to target the symptom. Wouldn’t it be more comforting to be told that “this sounds to me like a case of Gut dysbiosis so we need to redress the balance and possibly reseed your gut flora with a good probiotic,and put you on a detox program to help your liver out”.
Good vs Bad Bacteria
In the previous article I intimated the existence of Beneficial flora and opportunistic or commensal flora where the latter can ‘bat either side of the plate’, if kept in check by our beneficial flora the commensal colonies remain harmless and in some cases assist the host in a beneficial way thus becoming an extension of our beneficial flora colonies. However, if the beneficial flora, our guardians become compromised or damaged then the commensal colonies overgrow and cause harm. Opportunistic flora as part of their normal metabolism create toxic by-products which are neutralized under normal healthy conditions but if an imbalance occurs these toxins begin to cause trouble. Histamine ( a metabolite from an amino acid ) is a nitrogenous compound involved in the inflammatory response process and a central mediator to Pruritus ( Itching ). It is produced by Basophils ( white blood cell Leukocytes ) and Mast cells. Mast cells patrol the body looking for the enemy and spray histamines when they encounter them, inducing a greater blood flow to the infected area creating an inflammatory response.
Particular species of our commensal bacteria also produce histamine including Lactobacillus Casei, Lactobacillus delbrueckii, Proteus family,E.Coli family and Staphylococci. A lot of food contain histamines including fermented foods, dairy, some vegetables and fruit, some fish, and there are even foods that promote histamine production such as fruit ( grapefruit,papaya ( yuk , my favorite ), pineapple ( yuk, another favorite ), banana etc, vegetables like spinach,eggplant,avocadoes. Nuts and tea. On the other hand some beneficial bacteria actually degrade histamine which becomes a natural treatment or prevention against an allergic response. These bacterial histamine degraders include Bifidobacterium infantis and Bifidobacterium.longum.
Our body joins the histamine fight by producing Diamine Oxidase an enzyme produced by epithelial cells that also degrades histamine and another enzyme N-methyltransferase which exists in most body tissue providing your Methylation * process is working efficiently. The most histamine produced is within our gut flora so it is crucial that this is kept balanced ( I know I sound like a scratched vinyl record but I will continue to mention it ) or histamine intolerance could ignite and then life could become miserable involving a diet elimination program as well as a course of Probiotics ( another topic for future articles).
The Basics of Methylation
In essence Methylation is a cyclical process that occurs daily, in the body millions of times/second to satisfy the body’s crucial requirements.
Methylation involves the following recipe ingredients:
- Methionine ( an essential amino acid absorbed from our diet ( nuts, meat, cheese, fish, eggs, beans, spinach, broccoli, seaweed, cauliflower, Parsley for example ).
- Folic acid from dark green leafy vegetables
- MethylCobalamin (B12) from red meat
Methylation cycle involves :
- MTR gene that provides instructions to make Methionine synthase that converts Homocysteine into Methionine, and MTRR gene to produce methionine synthase reductase
- MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase used for the intermediary folate cycle
- Magnesium/ATP from the cells mitochondria
- Methionine can then produce SAMe (S-Adenosyl methionine which is the main methyl donor to the bodies methylation cycle.
- Methionine has attached a methyl group ( 1 carbon atom + 3 hydrogen atoms ) ** which is used for every required function of Methylation.
The basic idea is shown in Fig 1, however this is not a complete representation since there is also a short cut route from Homocysteine to Methionine that uses BHMT enzyme.
Fig 1: Basic Methylation Cycle
**Methyl groups are likened to clothes ( what is he talking about ?? ). For example, if I am invited to a job interview I would obviously wear a suit and tie, but If I was playing Tennis I would wear a dry fit shirt and a pair of shorts. So the change of clothes to suit the occasion is the Methyl group.
This Methylation cycle occurs within each cell and 85% of methylation occurs in the liver, the rest in the kidney and testicles. The purpose for 80% of Methylation is to produce creatine for muscles, and to maintain brain and neurological health, the remainder covers some 200 other functions that include dopamine and estrogen degradation, production of Norepinephrine, Melatonin, Carnitine, Coenzyme Q10 ( for the heart ) and gene switching.
So, why I am explaining this, and what has this got to do with our microbiome?
Two reasons, our microbiome if unbalanced can screw up the methylation cycle and in addition our bacteria also has a Methylation cycle and one of its purposes is to create a restriction modification cycle to defend itself against foreign DNA which occurs when a virus ( a vicious parasite ) that needs other bacterial cells for its duplication; these are called Bacteriophages – more on this intrigue in Part 2.
The Dangers of Bacterial Overgrowth
So a small intestinal bacterial overgrowth can cause an overload of Histamine as well as an impact on the Methylation cycle by increasing folate levels, interfering with MTHFR pathways and a decrease in B12 absorption, not to mention the negative influence on our genes. For example, the gene COMT which relates to methylation, provides instructions to make an enzyme catechol-O-methyltransferase which is used to control the production and degradation of hormones, so excess Histamine production can interfere with this process. An imbalanced gut flora allow commensals to produce too many toxins that disturb our methylation cycle causing anxiety, tension, insomnia, pain, fatigue and brain fog.
There are 3 big microbial by-products that impair methylation which are
- Phenols, if an imbalance gut is causing more phenols to leak into the body it will slow the clearance of Estrogen and stress hormones, since phenols from the diet (Resveratrol or Tea Catechins) or even worse from poisonous health products and cleaning products compete with estrogen and adrenalin/dopamine for metabolism through the COMT pathway.
- If too much or too little of the aromatic amino acids is produced by our bacteria tyrosine, phenylalanine and tryptophan it can have an impact on the brain and methylation.
- Bacteria such as Candida release toxic substances that are similar in shape and function as formaldehyde and ethanol. The aldehyde type substance is metabolised by the same enzymes that metabolise neurotransmitters ( Dopamine, Seratonin, Adrenalin ) so they compete, thus disrupting methylation and slowing down the metabolic process. Ethanol ( alcohol ) depletes the body of zinc.magnesium,folate and the B vitamins, but they to get converted into aldehydes that can cause DNA damage.
So in effect gut microbe by-products can increase the level of stress hormones. There is another lurking danger which involves alcoholic effects Candida love to munch on sugar and its digestion is a fermentation process, so it converts glucose into ethanol and its by-product is acetaldehyde. Individuals that appear to be under the influence of alcohol after a meal containing carbohydrates have in fact Candida overgrowth which makes sense, since yeast is used in the fermentation process of making beer. In terms of methylation, pure ethanol in low concentration (less than 5%/vol) such as beer, is a mild stimulant of acid secretion of the stomach, but higher concentrations of ethanol such as in Spirits ( Whiskey, Gin,Cognac) has an anti-stimulatory to a mild inhibitory effect on acid secretion. This means that there is a potential negative effect on stomach acid secretion which can deplete the creation of methyl groups In addition the typical poisonous ‘Western diet’ can also upset Methyl group creation.
Dysbiosis can cause Serious Problems
Gut microbiome activity converts other toxic substances such as Dimethylamine, Piperidine, Pyrrolidine,Tyramine and Octopamine from the metabolism of amino acids Choline, Lecithin, Methylamine, Lysine, Arginine, Ornithine and Tyrosine which cause depression and behavioral problems. Natasha Campbell Mcbride’s wonderful work with GAPS children, inform us that opportunistic flora such as Candida Albicans, Bacteroides,Clostridia, Streptococci, and Staphylococci have been found in their stool samples.
However stool samples are samples from the lumen of the bowel but little research has been performed on the commensal microbial species within a dysbiotic gut that live on the mucosal wall. Dr Campbell-Mcbride goes on to say that the most ubiquitous opportunistic bacteria are the Bacteroids such as Bacteroides melaninogenicus and Bacteroides fragilis that are always hanging around the mucosal areas of the body. They can always be found around infected tissue of the digestive tract such as abscesses, ulcers,urinary infections,peritonitis, mouth and gum infections and they always hang out with worse ‘Thugs’ Clostridia which are even more damaging ( although Clostridium tetani of Tetanus fame also exists within a healthy gut and its tetanus toxin cannot penetrate our mucosal firewall. However the compromised microbiomes of GAPS children it can. The work conducted by Dr Campbell-Mcbride involves Autism and a number of other psychological conditions suggesting a powerful link between Autism and gut damage.
Are there any drugs that actually improve your Microbiome?
A drug exists which is an antibiotic and antiprotozoal ( anti-particular bacterial microbe ) called Metronidazole (marketed brand name Flagyl) which can be used to reduce Clostridium difficile, a bacterial strain that can cause a form of fatal colitis. This drug can reduce autistic symptoms and improve digestion but as soon as the drug treatment is stopped the symptoms return..Surprise, surprise. The good news is that the drug is inexpensive ( $26 for a 10 day treatment program ) and for $26 you can enjoy the pleasures of the following :
- Agitation, back pain, blindness, blurred vision, burning, numbness, tingling, or painful sensations in the hands or feet, changes in speech patterns, confusion, convulsions, decreased vision, depression, dizziness, drowsiness, eye pain, fever, hallucinations, headache,irritability,lack of coordination, nausea
- seizures, shakiness and unsteady walk, slurred speech, stiff neck or back. trouble speaking unsteadiness, trembling, or other problems with muscle control or coordination, unusual tiredness or weakness, vomiting, weakness in the arms, hands, legs, or feet
- Black, tarry stools, blood in the urine or stools, body aches or pain, chills, clumsiness or unsteadiness,
- difficulty with breathing, ear congestion, feeling of pelvic pressure, frequent or painful urination,
- loss of voice, nasal congestion, pinpoint red spots on the skin, runny nose, skin rash, hives, redness, or itching, sneezing,stomach and back pain (severe),unusual bleeding or bruising,vaginal irritation, discharge, or dryness not present before taking the medicine
- Bleeding gums, bloating, chest pain, constipation, cough, dark-colored urine, fast heartbeat,indigestion
- loss of appetite, painful or difficult urination,pains in the stomach, side, or abdomen, possibly radiating to the back, sore throat,sores, ulcers, or white spots on the lips or in the mouth,swollen glands,yellow eyes or skin.
There is another drug available called Vancomycin, also an antibiotic and also used to treat Clostridium difficile colitis but it is more expensive, and it, like Metronidazole is on the World Health organisations List of essential medicines. As I understand it Vancomycin is made by a soil Bacterium Amycolatopsis orientalis.
Two Important Enzymes
I want to draw your attention toward 2 enzymes that are related to stress namely ACE (Angiotensin Converting enzyme) and GAD (Glutamic acid decarboxylase).
GAD is an enzyme responsible for producing GABA (Gamma aminobutyric acid) which is a crucial inhibitory neurotransmitter in neurons and the beta pancreatic cells. It is also an identified ‘Perp’ in autoimmune disease and Type 1 diabetes ( more of these conditions in Part 2 of this article).
Angiotensin is responsible for vasoconstriction ( blood vessel constriction) triggered by the Autonomic Nervous system ( Sympathetic branch) to regulate arteriole diameters, in order to increase or decrease blood flow to various organs. A normal intelligent function of the body I might add, but of course this action will obviously alter blood pressure. Angiotensin I is a protein produced by the liver and released into the blood. ACE converts Angiotensin I to Angiotensin II for the purpose of blood flow regulation. Since Allopathic medicine is on the ‘warpath’ to keep everybody on the same blood pressure ( because it causes strokes ???) they prescribe ACE inhibitors to lower blood pressure and in the words of Dr Bergman ‘to have the audacity to second guess the body’. Furthermore, the other functions of Angiotensin II is Growth induction, cell migration, mitosis of vascular smooth muscle cells, increased synthesis of collagen in fibroblasts, as well as some involvement in myocardium repair process following a myocardial infarction.
The Effect of Stress on the Microbiome
Stress enzymes, GAD ,ACE and the Angiotensin protein are also related to adrenal stress and Aldosterone ( an adrenal activated hormone that affects blood pressure regulation by signalling the kidney/colon to increase the amount of sodium released in the blood and the amount of potassium released into the urine. In addition, it triggers the uptake of water and sodium into the blood to increase blood volume, and helps in the maintenance of PH and Electrolyte levels. Thus Aldosterone is linked to 2 other hormones Renin and Angiotensin forming the rehydration axis; the Renin-angiotensin-aldosterone system which is activated upon detection of low blood pressure This axial system kicks in to regulate plasma sodium concentration and arterial blood pressure …wait, one of the side effects of the ACE inhibitor is hypotension ( low blood pressure ) so the inhibition of the enzyme to produce Angiotensin must result in the collapse of this functional axis.
When sympathetic stress is activated, 50% of the stress hormone substance is sprayed onto the microbiome like fertilizer which enhances the growth of the bacteria included the opportunistic flora. I read an article that described taking a sample of E.Coli from the gut and placing it into 2 Petri dishes and one was sprayed with Adrenalin, then left 24 hours. Then the sprayed petri dish was examined and the E.Coli had grown 10,000% faster than the other unsprayed culture.
Furthermore, this particular article by Dr Rostenburg of Red Mountain natural medicine clinic also explained how, if the host is under stress, it allows our microbial ‘thieves’ to steal our iron directly from the hosts armoured trucks Lactoferrin and Transferrin. Lactoferrin ( A natural iron binding protein found in human milk and other human secretions like tears and saliva) is an integral part of the immune system since white blood cells release it to inflammation sites to provide anti-microbial/anti-inflammatory protection. It also is part of the microbiome control mechanism to ensure balance. Transferrin is a true iron transport which is used to control the level of free iron in biological fluids. It is a bold face iron ‘Stick-up’ by our microbial buddies..what was I saying about keeping your enemies closer.
In Part 2 we will go into more detail on how a breach in the epithelial can cause other diseases like Autoimmune and Autism.
Dr. Carpenter: Agent Scully.
Scully: Oh, Dr Carpenter, I fell asleep.
Dr. Carpenter: I’ve done some work. These are the DNA sequences from the bacteria sample you brought in. You seem to know something about molecular biology. Do you know what you’re looking at?
Scully: Yeah, I think these are genes.
Dr. Carpenter: Right. They’re called base pairs. Each pair is made up of something called a nucleotide. Only four nucleotides exist in DNA, four. And through some miracle of design that we have yet to fathom, every living thing is created out of these four basic building blocks. What you’re looking at is a sequence of genes from the bacteria sample. Normally, we’d find no gaps in the sequence. But with these bacteria we do.
Scully: Why is that?
Dr. Carpenter: I don’t know why. But I tell you, under any other circumstances my first call would have been to the government.
Scully: What exactly did you find?
Dr. Carpenter: A fifth and sixth DNA nucleotide – – A new base pair. Agent Scully, what you are looking at, it exists nowhere in nature. It, would have to be by definition… extraterrestrial.
The X-files, Episode “The Erlenmeyer Flask”
Author: Eric Malouin
Reviewed by Dr. John Bergman