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How Does Methylation Affect Gut Health?

How Does Methylation Affect Gut Health?

Brain-GutOur gut is a central organism in our body, and it includes the oesophagus, stomach, and intestines. All   these parts work together so we can both eat and digest our food. The main function of the gut is to   keep the system functional and balanced.

Gut health is essential for

  • our immune system,
  • absorption of nutrients,
  • absorption of B12
  • and gut/brain connection

We have discussed the role of the gut in other blogs.  In this blog we hope to impress upon you that the microbial mechanisms and key metabolites that shape the composition of the human gut microbiota are still largely unknown, impeding efforts to manipulate dysbiotic microbial communities towards stability and health. However, research is demonstrating that vitamins, (which by definition are not synthesized in sufficient quantities by the host) can – DRUM ROLL…….. mediate fundamental biological processes in microbes and represent an attractive way for reshaping microbial communities.

In this blog we discuss how vitamin B12 (cobalamin) impacts diverse host-microbe symbioses (harmony). Cobalamin is synthesized by some human gut microbes and is a precious resource in the gut. That said – while cobalamin does make an unrecognized contribution in shaping the structure and function of human gut microbial communities, it does not appear to be created in significant quantities. This is one challenge for those whose methylation cycles are challenged.

What Is Methylation

We have talked about methylation in other blogs, please see the end of this blog for further reading.

In summary Methylation is a simple biochemical process, which is essential to our overall well-being. When it is out of balance, it can cause several different health problems. Methylation is where a molecule called a ‘methyl group’ is added to another substance, such as DNA or protein, so this substance can function.

Genetic Methylation 

Epigenetics refers to chemical processes that influence how our genes work, with or without changing our DNA. Methylation is an example of one epigenetic process that is necessary for our DNA to work perfectly. It can be an essential link between our environment, nutrition, and diseases.

Importance of Methylation 

Methylation in DNA regulates gene expression by recruiting proteins involved in gene expression or inhibiting the binding of transcription factors to DNA. The comprehensive regulation of DNA methylation is necessary for normal cognitive function.

To increase DNA methylation, these basic nutrients should be added to the diet:

  • Folate
  • B vitamins
  • Choline

Symptoms of Malfunctioning Methylation

(This could be insufficient methyl groups or an inability to use the methyl groups you have).

  • Depression
  • Anxiety
  • Histamine intolerance
  • Cancer
  • Hormone imbalance
  • Poor detox capabilities
  • Infertility
  • Multiple miscarriage
  • Chronic Fatigue
  • ADD/ADHD
  • Multiple chemical sensitivity
  • Birth defects
  • Low energy levels

And much more

How To Fix Methylation Problems

Our genes can make you susceptible to having a defect in your methylation processes, however it is your environment that influences whether these genes express or not. Let me say that again – it is your environment that influences whether these genes express or not. We are not victim to our genes.

For example, infection, stress, lack of sleep, poor gut function, toxins you are exposed to, the food you eat, what you drink, can all put more demands on your methylation cycle. So, if you have a deficiency naturally (perhaps because of MTHFR), you will find it harder to catch up and the more environmental factors may impact you.

Many things can help to take the demand off your methylation cycle, i.e.:

  • Eat well
  • Stay hydrated
  • Get enough sleep
  • Get plenty of exercise (but not too much)
  • Manage stress with meditation, yoga, mindfulness.

Foods that help in improving the methylation in the body include:

  • Avocado
  • Brussels sprouts
  • Broccoli
  • Asparagus
  • Legumes
  • Green leafy vegetables, etc.

How Does Methylation Affect Gut Health?

What is Leaky Gut?

We have blogs on leaky gut as well however in summary: Leaky gut occurs when the intestinal lining gets damaged. The digested food and microbial flora that are meant to be confined to the gut don’t stay in the gut but ‘leak out’ and create an immune response. We might see this with a high Zonulin reading in your stool test for example. The condition is also known as intestinal permeability. This results in the inflammation and may cause inflammation throughout the body, because toxins enter the bloodstream when they shouldn’t be able to. This can affect your immune system and cell membranes which can lead to further health issues.

Causes of Leaky Gut

There are several different factors that can contribute to leaky gut:

  • Imbalanced gut bacteria
  • Stress
  • Pesticides
  • Food allergens

Photo by Brooke Lark on UnsplashThese factors place stress on the digestive systems.

So how is this all linked to methylation?

Methylation And Leaky Gut

S-adenosyl-L-methionine (SAMe) is a compound found naturally in the body. SAMe helps produce and regulate hormones and maintain cell membranes. 

Methylation can affect SAMe’s production and cause intestinal problems. This can result in the inability to digest food and stay healthy, nausea, vomiting and diarrhoea. Other symptoms can include:

  • Decreased memory
  • Bloating
  • Headaches
  • Mood fluctuations
  • Joint and muscle pain
  • Autoimmune diseases.

A severe deficiency of SAM can lead to histamine intolerance, which results in food allergies, hives, skin conditions like eczema, anxiety, period pain, PMS, asthma and much more.

SAM is required for the breakdown of histamine, so when SAM is in short supply, the histamine isn’t broken down, leaving extra amounts in the body. This creates histamine intolerance.

Nutrients Needed For Proper Methylation

Proper methylation plays a key role in keeping the body functioning well. If you are suffering from a leaky gut, it’s important to improve the function of the gut, the quality of the mucosa and eliminate any dysbiotic bacteria. This helps heal the gut so you can move into the recovery phase.

The following nutrients will help improve methylation, and in return, improve gut health:

  • Magnesium
  • Riboflavin 5’-Phosphate (active vitamin B2)
  • Pyridoxal 5’-Phosphate (active vitamin B6)
  • 5-MTHF (active folate)
  • Methylcobalamin (active vitamin B12)
  • Betaine (also known as trimethylglycine)

Please see our blog on Supplements – They Mean Well.

The Importance Of Vitamin B12 For Methylation

The human body does not synthesize vitamin B12, yet it’s needed for different body functions, including gut health. Also known as cobalamin, vitamin B12 deficiency is more often seen in vegetarians, as the vitamin is mainly present in:

  • Liver
  • Fish
  • Eggs
  • Chicken

Role of Vitamin B12 (Cobalamin)

Cobalamin plays an active role in:

  • synthesizing DNA and maintaining the health of blood cells and neurons
  • also plays a major role in synthesizing gut bacteria that help in the digestion of the protein, as well as maintaining the health of the gut.

The intricate vitamin has a complex structure. It requires 30 different genes in a bacterial genome to make vitamin B12.

Here is a list of our gut bacteria that produce vitamin B12:

  • Firmicutes: Clostridium difficile, Faecalibacterium prausnitzii, Ruminococcus lactaris, Lactobacillus plantarum, L. coryniformis, and L. reuteri.
  • Fusobacteria: Fusobacterium varium.
  • Bacteroidetes: Bacteroides fragilis and Prevotella copri.
  • Actinobacteria: Bifidobacterium animalis, B. infantis and B.longum.

These bacteria are present in the large intestine region, while the receptor of vitamin B12 is present in the small intestine. They absorb it after protein digestion in the stomach. 

Vitamin B12Deficiency of Cobalamin

A deficiency can lead to several symptoms, such as nausea, vomiting, diarrhoea, weight loss, sometimes constipation, memory problems and depression. If left untreated, it can also lead to death. Researchers have also found that deficiency of cobalamin can result in neurologic disorders.

Knowing this, it is important ensure your levels of vitamin B12 are healthy. Start by eating foods that are rich in cobalamin and take vitamins on top to supplement and maintain gut health.

Folate And The Gut 

Folate is vitamin B9, which is needed to make DNA and other genetic material. Folate deficiency is the most common vitamin deficiency in developed countries, resulting from low intake, malabsorption and/or alcoholism.

Bacteria play a key role in the production of folates in the colon region. If this bacteria is lacking in the body, then the folate isn’t received and it can result in conditions such as anaemia, slowed growth, neural tube defects, weight loss, diarrhoea, cancers and neurological issues like anxiety and depression. Monoglutamylated folate is produced in the gut region at a high rate. The intestinal microbes synthesize the folates and absorb it into the bloodstream where it is used in the body. 

So now you can understand how gut issues might impact your folate. 

Absorption of Folate

The absorption of folate occurs first in the duodenum (the first and shortest section of the small intestine), then in the jejunum region (the larger part of the small intestine), and in the end, it reaches the colon. If gut health is poor, chances are there will be a lack of the folates in the body. If there is inflammation present or a person is suffering from diseases, such as colon cancer, then a reduction of folate will occur. 

Key Genes That Affect Our Microbiome

The body’s microbiome, composed of microbial cells that number in the trillions, is involved in human health and disease in ways that are just starting to emerge. The microbiome is assembled at birth, develops with its host, and is greatly influenced by environmental factors such as diet and other exposures. Recently, a role for human genetic variation has emerged as also influential in accounting for interpersonal differences in microbiomes. Thus, human genes may influence health directly or by promoting a beneficial microbiome. Studies of the heritability of gut microbiotas reveal a subset of microbes whose abundances are partly genetically determined by the host.

As we have seen, the microbiome shapes human health and protects us from disease. Recent studies suggest that variations in human genetics are also pivotal in the microbiome. Several studies show a clear relationship between microbial genes and human genes. For example, there is one notable bacteria, called bifido bacteria, which are related to the human lactase nonpersister genotype that leads to intolerance of lactose.

MethylationHere are some other genes that affect our microbiome:

Hydrochloric acid – BHMT or betaine homocysteine methyltransferase is a zinc dependant enzyme that is highly expressed in the liver, kidney, and lens of the eye. This gene is used to catalyse the transfer of methyl from betaine to homocysteine. The result is the production of dimethylglycine and methionine. The process of remethylation is critical for the synthesis of S-adenosyl methionine (SAMe), the methyl donor for most methylation reactions. This gene is essential in helping you to recycle homocysteine and from a clinical perspective people with this polymorphism do really well on betaine hydrochloride which is essential for absorption of nutrients.

If you’re considering adding a betaine HCL supplement to your treatment regimen, make sure to talk to your healthcare provider and pharmacist before you make a big purchase. With their help, you can make an educated decision considering any potential risks or medication interactions based on your personal medical history.

Top Food Sources. Which foods contain betaine?

Here are 12 of the best food sources of betaine:

  1. Wheat Bran — 1/4 cup uncooked (about 15 grams): 200 mg
  2. Quinoa — About 1 cup cooked or 1/4 cup uncooked: 178 mg
  3. Beets — 1 cup raw: 175 mg
  4. Spinach — 1 cup cooked: 160 mg
  5. Amaranth Grain — About 1 cup cooked or 1/2 cup uncooked: 130 mg
  6. Rye Grain — About 1 cup cooked or 1/2 cup uncooked: 123 mg
  7. Kamut Wheat Grain — About 1 cup cooked or 1/2 cup uncooked: 105 mg
  8. Bulgar Grain — About 1 cup cooked or 1/2 cup uncooked: 76 mg
  9. Sweet Potato — 1 medium potato: 39 mg
  10. Turkey Breast — 1 breast cooked: 30 mg
  11. Veal — 3 ounces: 29 mg
  12. Beef — 3 ounces cooked: 28 mg

Oxalates – there are many genes that affect the breakdown of oxalates and now that we are spraying our foods with glyphosate, we are jamming up our oxalate pathway. This leads to an excess of oxalates (which can cause gut pain, thyroid issues, joint pain, recurrent candida, low Sulfur and much more). This is significant because oxalates bind to B6, Zinc, iron and make them unavailable for use. They also affect our calcium stores.

Oxalates are found in nuts, seeds, and many vegetables like carrots, celery, spinach, and potatoes. High levels of oxalates can cause kidney stones, autoimmunity, inflammation, mineral balance, connective tissue integrity, urinary tract issues, and poor gut function. Since our focus is on gut health, higher levels of oxalates will further increase the absorption of oxalates in the body. Oxalates are sharp crystal shapes and can damage our tissue and cell membranes.

Sulfur is an incredibly important substance for our body. Sulfur acquisition is crucial to both humans and their symbiotic gastrointestinal tract (GI tract) microbiota. The colonic compounds consisting of Sulfur are organic, e.g., bile, mucins, dietary amino acids, or inorganic, Sulfite/Sulfate.

H2S or hydrogen sulfide is produced, which is the end product of anaerobic microbial degradation of the Sulfur compounds. This happens when the process of assimilation of the Sulfur compounds fails to occur in the body. Gastrointestinal H2S is a neuromodulator and is crucial in controlling the physiological responses, like epithelial cells’ health and motility. The exact role and fate of sulfide in the human GI tract is not clear and until now, there are only few sulfidogenic microorganisms described that use Sulfate or Sulfite as terminal electron acceptor, such as Desulfovibrio spp. or Bilophila spp. (via taurine).

Microbial fermentation leads to an increase in the histamine content of foods. The process is caused by some types of bacteria that are present in the gut, known as histamine producing bacteria.

Some examples include:

  • Morganella
  • Enterobacter and citrobacter
  • Klebsiella
  • Lactobacillus species: Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus delbrueckii, Lactobacillus lactis, and Lactobacillus reuteri.
  • Enterococcus species: Enterococcus faecalis, and some types of E. coli.

The build-up of histamine takes place when the number of histamine producing bacteria outgrows the histamine degrading bacteria, like:

Bifidobacteria species: particularly Bifidobacterium infantis.

Lactobacillus species: Lactobacillus gasseri, Lactobacillus Plantarum, Lactobacillus rhamnosus, and Lactobacillus salivarius.

When this happens, the histamine producing bacteria fails to breakdown the excess of histamine, resulting in the occurrence of histamine intolerance symptoms like allergies, gut pain, cramping, diarrhoea, flushing, headaches and much more.

Man vs MicrobiomeIn  Conclusion:

Our gut microbiome is a combination of fungi, and trillions of bacteria and other microorganisms. It plays a crucial role in your health by controlling the digestion process, keeping your overall immunity strong and supporting mental health. Any imbalance in your gut microbiome may lead to high blood pressure, weight gain, high cholesterol, depression, anxiety and much more. Keeping your gut healthy is crucial and for that, you need to have a good quality diet. Initially you may have a restricted diet to help your gut heal, however your long-term diet should consist of healthy, organic (or as much as you can afford) foods, fruits, vegetables, and whole grains. Incorporate protein from eggs, fish, chicken, lentils, legumes, and fermented foods where possible. Include pre and probiotics in your diet to support a healthy microbiome. Try to keep the stress under control, exercise, get sufficient sleep and don’t ignore symptoms that may lead to bigger issues later when it comes to your gut.

For further information please see our sequence of blogs on these topics:

What is Leaky Gut?

What Is The Gut?

Why Is Everyone Banging On About Gut Health?

Whats This Microbiome Thing?

The Mushroom Craze

Is Your Gut Making You Feel Unhealthy Paranoid Or Stressed Out?

Should I be Freaking Out About my Genes?

How to Boost Your Glutathione?

How Can I Improve Methylation?

What is Oxidative Stress?

Are Your Methylation Processes Bang On, OR Are They Off the Rails?

 

. . . . .
Yours in health…
Jennifer Barham-Floreani
Bach. Chiropractic, Bach. App Clinical Science
Registered internationally, no longer practicing as a chiropractor in Australia.

 

 

References:

 

Degnan PH, Taga ME, Goodman AL. Vitamin B12 as a modulator of gut microbial ecology. Cell Metab. 2014;20(5):769-778. doi:10.1016/j.cmet.2014.10.002

Folic acid and folate https://mpkb.org/home/food/folic#%3A~%3Atext%3DFolic%20acid%20is%20the%20synthetic%2Cthat%20make%20up%20their%20DNA

Goodrich JK, Davenport ER,Clark AG, and Ley RE (2017).The Relationship Between the Human Genome and Microbiome Comes into View. Annual Review of Genetics. Vol. 51:413-433 (Volume publication date November 2017)

Pérez-Miguelsanz J, Vallecillo N, Garrido F, Reytor E, Pérez-Sala D, & Pajares MA. Betaine homocysteine S-methyltransferase emerges as a new player of the nuclear methionine cycle. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research, Volume 1864, Issue 7,2017, Pages 1165-1182,

Sulfur metabolism in human gut microbiota. https://www.wur.nl/en/project/Sulfur-metabolism-in-human-gut-microbiota.htm

 

 

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