Nutrients in Food and their bodily purpose XIX (Methylation V and the Microbiota I)

I have always said that, to understand whats going on today we must look into what has gone before. Climate change is a classic example.  Instead of panicking over global warming and needlessly spending huge amounts of money on attempting to reduce human induced carbon dioxide emissions, and realise that this is plant food and not a pollutant, and our history clearly shows that cold and hot periods are cyclical over time, and is quite normal.  Medicine today has conveniently erased the past that recognised the value of nutrition, biochemical individuality, and the vital importance of adapting to the environment. Robert O. Becker (1923-2008) a great orthopedic surgeon and researcher in electrophysiology and electromedicine states that with all advances in technology medicine has left behind ‘MEDICINE’S HUMANITY’:

“ The promise to humanity of a future of golden health and extended life has turned out to be empty and replaced by a widespread global population that are suffering with degenerative disease that have replaced infectious diseases that once plagued the planet.”  

Robert O Becker

 

“ You can look into every caviolea of the human organism and understand the immense complexity of how it works, but until modern medicine banishes this tragic course of pharmacology and embraces the true medicine of the body it will continue to blaze a trail of eventual extinction”.   

Eric Malouin

 

“ The failure of technological medicine is due, paradoxically, to its success, which at first so overwhelming that it swept away all aspects of medicine as an art.  No longer a compassionate healer working at the bedside and using heart and hands as well as mind, the physician has become an impersonal white gowned ministrant who works in an office or laboratory.”  

Robert O Becker

Introduction

So let us count how many people on the planet are suffering from some degenerative disease such as neurological disorders ( Alzheimer’s, Parkinson’s), strokes, multiple sclerosis and epilepsy etc on the planet….> 1 billion people…1 billion people. and a further 6.8 million…6.8 million. are dying each year from some disease or another.  Wait a moment…. 1 billion people..that is a ⅙ of the entire planet.   Robert O.Becker wrote the words above in a book called ‘Body Electric’ with Gary Selden in 1985..38 years ago.  In 1985, the world wide population was 4.8 billion, so how many were suffering then from some form of degenerative disease, and how many were dying annually from their malady ?. I am sure these statistics are discussed at the bilderberg conferences along with other world affairs, and I wonder what their remarks are ?… maybe it’s a methodology to maintain global population control perhaps.


The intricacies of our microbiota

 

We have mentioned how the imbalance of our bacterial colonies that make up our internal microbiota can cause problems with the host in a variety of ways.  It makes perfect sense that this imbalance can screw up the methylation cycle. Our bacterial symbionts also have a Methylation cycle, and one of its purposes, is to create a restriction modification cycle to defend themselves against injected foreign DNA into its own cells by bacteriophages, for the purpose of viral replication.  Physicians and patients in general tend to ignore these huge bacterial colonies, but they do this at their peril, since these organisms are as alive as the hosts mammalian cells, and have a great influence on host function. This is most apparent when considering autoimmune conditions, but generally conventional medicine refer to these conditions as idiopathic and incurable, despite the source of the problem is staring at them when specific antibody production is discovered from blood tests.

Rapid bacterial gene transference

It is important to be aware that these bacterial colonies are vast in bacterial numbers, versatile and highly adaptable.  In order to speed up their replication they can streamline their DNA gene pool by simply sloughing off unwanted genes, commensurate with their particular environment, under the same principle as not using a limb for a while..use it or lose it. If their environment changes, and they need these discarded genes, by lateral gene transfer they can simply get them back by way of bacterial conjugation or consuming dead cells from other bacteria, a process that can be completed within hours. Although, consuming dead cells runs the risk of consuming damaged cells,  so bacteria prefer to swap genes. What this means is, that bacteria subjected to antibiotics, adapt quickly to acquire the necessary genes to protect themselves, which is why antibiotics are only temporarily effective. This versatile gene transfer can occur between different species, genera and domains so there is no reliance on slow vertical gene transfer as in our own mammalian genes. What this means is that potentially, speciation ( formation of new species ) can occur rapidly. The very reason for this fast lateral gene transfer as mentioned above is for rapid replication which is a fundamental concept of survival and competition with other species.  If bacteria were to keep all of their genes as ‘just in case’ paradigm they would be too slow in colonization and less competitive. It is also known that this bacterial behaviour also maintains a practical genome size, that is not too large, and in the order of transcribing some 9000 genes, compact, that can adapt quickly.

The blame game – defective genes the culprit yet again.

We have already established that DNA methylation, histone modification and chromatin remodelling  represent the mechanism of epigenetic gene expression. Furthermore we have also well established the influence on many varied host health conditions by the dark side of our microbiota in the guise of pathogenic flora. It goes without saying, although we have said many times before, a symbiotic host-microbiota relationship is crucial for mammalian homeostasis. Looking for variances or transcriptional differences between a sample genome and a reference genome is useful for the progression of human physiological knowledge, but not as a means to lay blame on these variances as a cause of human disease. How the host handles its environment endogenously and exogenously in terms of nutrition and toxicity is far more relevant, which ultimately will affect the epigenetic expression of these genes anyway.  The new fad of genetic testing to ascertain disease predisposition based on a large sample of population is in my opinion scientifically flawed, since some results pinpoint some conditions that are clearly of gut dysbiosis origin and not caused by ‘defective genes’ even if they are shared among a number in a population sample.

Microbiota (Microbiome) basics

At this juncture I would like to recall some previous text from 2 years ago from the articles ‘Microbiome’ :  The Microbiome in the human organism is a vast ecosystem of microorganisms that live and thrive throughout the long tunnel that runs from our mouths to our anus like microbial wallpaper. Externally there are vast colonies that live on our bodies, in our mouth,on our skin, and under our arms. So not only are we a complex chemical factory but we are also a walking garden of Bacteria. Our microbial ecosystem exists to help us digest our food, regulate our immune system, protect us from harmful pathogens and manufacture essential vitamins. Some references identify 1000 different species with 7000 different strains.  A well nourished gut flora contains around 150 microbial species that has over 9,000 glycoside hydrolase enzymes and 2,000 polysaccharide lyases thus providing an estimated 60,000 carbohydrate degrading enzymes. Within the microbial communities it is known that there is cross feeding that occurs between species and its this nutritional interaction that ultimately shape the microbes metabolic capacity, where one species will digest a substance and secrete a metabolite ( chemical fingerprints of cellular processes ) such as lactic acid, acetic acid or butyrate which are then ingested by other microbial species to achieve optimal energy for the host.  Propionate is a microbial fermentation metabolite that is promoted by dietary intakes of Arabinoxylan ( a substance found from the outer shell of wheat and rice ) and available as a dietary fiber supplement, or Polydextrose which is a synthetic sugar fiber and only partially fermented by our gut microbes. Propionate, acetate and butyrate are all examples of SCFA (Single Chain Fatty acids) produced by bacterial fermentation of insoluble fiber from plant sources. It has been discovered that the majority of individuals with a healthy gut maintain 3 dominant bacterial phylum : Bacteroidetes, Firmicutes and Actinobacteria.

The Gastrointestinal epithelium the Major defensive line between outside (the world) and the inside (Body)

The entire gastrointestinal epithelium must be protected at all costs, since it is the major defense firewall between the outside world and the inside of our body.  It’s fundamental infrastructure consists of many Tight Junctions (TJ) knitted together by IEC (Intestinal Epithelial Cells ) referred to as Zonula Occludens providing a semi permeable entry for water, electrolytes, nutrient solutes, and keeping pathogenic microbes,toxins,antigens out.    It is coated with mucus, a ‘slimy’ material composed of Mucins ( Glycoproteins ), inorganic salts ( i.e Table salt NaCl ), suspended in water; it is our Mucosal Firewall. The protective purpose of Mucus is to bind to Bacteria to prevent bacterial colonization and repel damaging chemicals such as gastric acid (stomach hydrochloric acid).  In addition the IEC’s secrete a bicarbonate ion on their apical faces ( cell apex that face the lumen, the hollow part of the tract ) to maintain a neutral PH ( even though the lumen itself is highly acidic ). Regulation of smooth muscle within the epithelium is achieved by Prostaglandins ( a fatty acid compound ) which are synthesized within the mucosa from arachidonic acid ( an omega 6 fatty acid) by an enzyme called Cyclooxygenase providing cytoprotection ( pertaining to chemicals  used to protect cells from harmful agents) and to stimulate mucus and bicarbonate secretion.

Additional epithelium protection

Additional epithelial protection is afforded by Goblet cells scattered along the epithelial gut wall that not only secrete the protective mucus, but also produce Trefoil proteins ( small peptides ) that coat the IEC apical face protecting the epithelium from a range of toxins and drugs, playing a part in IEC repair.  Furthermore, Nitric acid also plays a role in mucosal integrity, when secreted by IECs, in response to ( for example ) a lumen dwelling pathogen Giardia Lamblia.  Within the crypts Paneth cells ( epithelial granulocytes- white blood cells containing secretory granules in its cytoplasm ) secrete antimicrobial peptides (AMPs) known as alpha-defensins  (Lysozymes) and Reg3 gamma (Regenerating islet-derived proteins), both used for pathogenic defense. Secretory immunoglobulin A ( sigA ) which are secreted by plasma cells located in the lamina propria ( inside the body) and transported into the lumen ( outside of the body) by IECs which have the property to block epithelial receptors preventing pathogenic attachment.


Mammalian-microbiota communication I (Shoring up the epithelium barrier)

In terms of the chemical crosstalk between the IECs and the microbiome, certain strains of E Coli a human fecal isolate, and probiotic strain, enhances protein expression within the epithelium, thus enhancing barrier integrity.  Metabolites secreted by Bifidobacterium infantis also provide barrier integrity.  Lactobacillus plantarum regulate barrier proteins providing protective effects by preventing and even reversing adverse effects from pathogens. Strains of Bifidobacterium lactis also provide protective effects.  These protective effects are in part due to the competition that occurs between probiotic beneficial bacteria and potentially pathogenic commensal bacteria for nutrients, required for growth and adhesion.  In addition, the metabolites secreted by the probiotic bacteria, go on to strengthen the Tight junctions (TJ) of the epithelium, through a cell signaling pathway that must be initiated by the probiotic bacteria, before treatment from metabolites are secreted from pathogens. One such bacterial strain that achieves this is a metabolite secreted by Salmonella enterica serovar Typhimurium ( However this strain itself can cause pathogenic harm).  Lactobacillus acidophilus and Streptococcus thermophilus assist infected IECs by treating them with protein inhibition to protect against TJ disruption.  Additional protection against barrier dysfunction is also provided by commensal bacteria species Bacteroides thetaiotaomicron, Lactobacillus rhamnosus and Bifidobacterium Longum.

Mammalian-microbiota communication II (Inter-kingdom signalling)

Inter-kingdom signalling refers to communication is conducted between the host and its symbiotic bacterial neighbors known as the microbiota.  We mentioned in a previous article a cell to cell communication mechanism that occurs within the bacterial colonies referred to as Quorum Sensing (QS), to coordinate gene expression within the bacterial population. However, the QS mechanism is utilized by Bacteria to communicate to the host as well.  Much of the research focuses on disease and pathogenic flora, because, like conventional medicine in general, they believe it’s their life long struggle to stamp out disease in our defective, or in this case ‘infected’ bodies, but, we all know that many millions are suffering with disease as a result of the pathogenic flora.  They overlook the fact that these negative conditions only manifest themselves when the the gut is allowed to become unbalanced, allowing the pathogenic colonies to take control, and by simply redressing the balance, allows the beneficial flora to take control, resulting in a healthier gut. Many research papers refer to the colonies as commensal, which we know from various articles, that these colonies tend to ‘sit on the fence’, and only join the winning colonies during the ‘competitive power struggle’ between beneficial and pathogenic colonies.  It is we, the host, that possess the power to decide who will be in control, by nutritional input and emotional control of our own lives, specifically with low or no stress. This bacterial ecosystem communicates with our own mammalian cells in a positive ( beneficial flora are in control) or a negative ( pathogenic flora are in control) manner. The symbiotic arrangement of beneficial bacterial species is paramount in nutrient assimilation and the development and regulation of our innate immune system.

Hormone signalling

The major interkingdom signalling pathway is by the use of hormones, whereby  bacterial signals can modulate mammalian cell signal transduction and host hormones can cross-signal with QS signals to modulate bacterial gene expression.  However, these signals can get hijacked by pathogenic bacteria to activate their virulence genes. The human peptide hormones include Insulin, Endorphins, Glucagon, Ghrelin etc, while steroid hormones include Testosterone, Estradiol, Aldosterone, Progesterone, Cortisol, Adrenocortical hormone, etc, and the Amine hormones include the catecholamines such as Adrenaline, Noradrenaline and Dopamine. From our discussions ( recalling some text from the articles ‘Microbiome’) concerning the gut-brain connection, this crucial link between our microbiome and the brain is bi-directional, insofar as the brain influences the ongoing development of our microbial colonies, while our microbial colonies manufacture neuroactive substances that include neurotransmitters ( serotonin ) and metabolites that influence the brain.  Our microbiome use the Vagus nerve ( this is the longest cranial nerve that connects the medulla oblongata just under the brain to the large intestine, the colon ) to communicate with the brain, while the metabolites excreted from our microbes influence the host immune system which maintains its own independent connection to the brain.

Serotonin production and function

We already know Serotonin (5-Hydroxytryptamine (5HT)) is manufactured in the gut by Bacterial species Lactobacillus and Bifidobacteria,  while Enterochromaffin cells (EC), that are found in the colon,  pick up a reserve of 5HT. This reserve is transported to the mucosa, lumen and circulating blood platelets, and in fact to 14 different 5HT receptor sites. 5HT provides signaling stimulus to a cell found in the GI tract called the Interstitial cells of Cajal ( ICC,  named after Santiago Cajal, Spanish pathologist), that work as an electrical pacemaker, generating electrical slow waves to the smooth muscle that make Peristalsis possible. The wave frequencies that occur in the GI Tract are:

  • Stomach –    3/minute
  • Duodenum – 11-12/minute
  • Ileum –         9-10/minute
  • Colon –        3-4/minute

5HT that is injected into the blood, maintains hemostasis control ( Blood clotting), vasodilation (blood vessel dilation, lowering blood pressure, regulated by the Autonomic nervous system Sympathetic branch throughout the body), pain and nausea perception, and influences bone development.  Interestingly, 5HT influences intestinal integrity, since epithelial cells secrete SERT (Serotonin selective Reuptake Transporter) which is also responsible for uptake in the brain. It also has been discovered that approx 2% of the neurons in the myenteric plexus( the major nerve supply to the GI Tract ) is serotonergic, where SERT acts like a sponge, removing the 5HT from the interstitial cells and soaking the epithelial cells.  It is known that 5HT is synthesized by the interplay between enterochromaffin cells (EC), the mucosal mast cells, myenteric neurons and 2 different Isoenzymes ( Isozymes or a multiple enzyme complexes ) of Tryptophan Hydroxylase ( TPH) that mediate neuronal activity but how it is accomplished is unknown.

Conclusions

The research of inter-kingdom signalling between the host and the microbiome is still in its infancy.  We are aware of these 2 dimensional influences, but there are still many unanswered questions. A great many diseases inflicted on mankind is of a microbiome-host dysfunction origin, but as long as conventional medicine continue to overlook this vital relationship, in terms of health of the human, the suffering, misery and needless low quality of life will continue.  My aim is to highlight how important this interface signalling is and attempt to make sense of how it is achieved despite the research emphasis on disease as opposed to health. This symbiotic/pathogenic relationship that exists between host and our bacterial ecosystem has existed since the existence of the first life forms that walked the earth, so it will always exist, and should always be a fundamental consideration in maintaining health during the lifespan of humans.  We will continue in the next article attempting to uncover more toward this crucial relationship and how it affects methylation.

We manipulate nature as if we were stuffing an Alsatian goose. We create new forms of energy; we make new elements; we kill crops; we wash brains. I can hear them in the dark sharpening their lasers.”

— Erwin Chargaff (1905-2002) Austro-Hungarian Biochemist who discovered base pairing in DNA.


Check out other Articles in this series:

Nutrients in Food and their bodily purpose I (Phenols)

Nutrients in Food and their bodily purpose II (Lignans, Triterpenes, Phytosterols, Carotenoids & Fats)

Nutrients in Food and their bodily purpose III (Phenolic acids, sulphur, sulphides,sulphoxides )

Nutrients in Food and their bodily purpose IV (Glucosinolates, Sulforaphane, Indole-3-Carbinol)

Nutrients in Food and their bodily purpose V (Lipid distribution, absorbed fats, Criciferous Veg)

Nutrients in Food and their bodily purpose VI (Nutrients required for Liver Detox)

Nutrients in Food and their bodily purpose VII (Seeds & the Omega Fatty Acids)

Nutrients in Food and their bodily purpose VIII (Nutrients required for cellular energy production)

Nutrients in Food and their bodily purpose IX (Water I Properties and Body fluids)

Nutrients in Food and their bodily purpose X (Water II Cellular Hydration)

Nutrients in Food and their bodily purpose XI (Water III Fluid filtration, reabsorption, excretion)

Nutrients in Food and their bodily purpose XII (Water IV Blood pressure, Blood volume regulation)

Nutrients in Food and their bodily purpose XIII (Water V Body Fluid Dysfunction

Nutrients in Food and their bodily purpose XIV (Dental Nutrients)

Nutrients in Food and their bodily purpose XV (Nutrients involved in Methylation I)

Nutrients in Food and their bodily purpose XVI (Nutrients involved in Methylation II)

Nutrients in Food and their bodily purpose XVII (Nutrients involved in Methylation III)

Nutrients in Food and their bodily purpose XVIII (Nutrients involved in Methylation IV)

Nutrients in Food and their bodily purpose XX (Methylation VI and the Microbiota II)

Nutrients in Food and their bodily purpose XXI (Superfoods: Wheatgrass)

Nutrients in Food and their bodily purpose XXII (Superfoods: Adaptogens)

Nutrients in Food and their bodily purpose XXIII (A look into our nutritional past Sir Robert McCarrison)

Nutrients in Food and their bodily purpose XXIV (Pregnancy: Nature vs Nurture vs Nutrition)


References/Acknowledgments :

  1. The Body Electric 1985 Robert O Becker & Gary Selden
  2. Power, Sex, Suicide 2005 Dr Nick lane
  3. Article Series ‘The Microbiome’ 2017 Eric Malouin extremehealthacademy.com
  4. Inter-Kingdom signalling: communication between bacteria and their hosts 2008 David Hughes and Vanessa Sperandio NCBI (Pubmed)
  5. How gut microbes talk to organs: The role of endocrine and nervous routes 2016 Patrice Cani and Claude Knauf  Molecular Metabolism Elsevier NCBI (Pubmed)

Author: Eric Malouin