ALL ABOUT BUTYRATE & WHY IT IS THE ULTIMATE MAST CELL STABLIZER

 

I have been working with mast-cell stabilizers now for nearly a decade.

When I was diagnosed with histamine intolerance and mast cell activation syndrome, I could not tolerate any of the prescription mast-cell stabilizers.

That led me to research the list of 21 anti-histamine foods that fight inflammation and stabilize mast cells nearly seven years ago.

That list highlights butyrate as a proven mast-cell stabilizer.

Since then, I have understood the paramount importance of butyrate, which maintains homeostasis in the body, not just of our mast cells but also our cell function in general.
 

WHAT IS BUTYRATE?

Butyrate is a type of short-chain fatty acid (SCFA).

SCFAs are the building blocks of fats that our cells need for energy.  Without sufficient SCFAs, our cells do not have the energy to function.

Butyrate is produced mainly by our microbiome, where it provides the energy for the cells lining our intestine to function.

Around 5 – 10% of butyrate enters the bloodstream, where it circulates not only to maintain energy homeostasis but also for our brain to function. 

Without sufficient butyrate, energy, gut, and brain, dis-homeostasis is inevitable.

THE MICROBIOTA

Butyrate is produced mainly by our microbiota.

Butyrate is produced indirectly through:

  • The presence of butyrate-producing bacteria
  • Feeding on prebiotic fibers (and intestinal mucus)
  • Cross-feeding and interacting with the whole microbiota.

Butyrate-producing bacteria typically belong to the firmicutes phylum. A detailed list of known butyrate-producing bacteria follows:

Of these, Faecalbacterium prausnitzii are significant butyrate-producers and amongst the most abundant bacteria in a healthy microbiome.

Interestingly, in an animal study, butyrate supplementation also directly altered the gut microbiota by increasing SCFA-producing bacteria and decreasing histamine-releasing bacteria.

Butyrate production will be hampered without sufficient butyrate-producing bacteria, the fiber in the diet, or a diverse and abundant microbiota.

 

GUT BARRIER

Our microbiome regulates the cells lining our intestines.

It is butyrate that provides the energy to the large intestine to grow, maintain, and protect the intestinal barrier.

Interestingly, certain butyrate-producing bacteria include Rosburia intestinalis and Eubacterium rectale, feed on the intestinal lining to produce butyrate.

Therefore, a healthy intestinal lining is crucial to some of the butyrate-producing bacteria that colonize and feed on it.

Without sufficient butyrate, leaky gut is inevitable.  

 

MAST-CELL AND IMMUNE MODULATION

 

Butyrate not only supports the gut barrier but also regulates mast-cells and the whole immune system.

The gut immune system needs to mount immune responses to pathogens while maintaining immune tolerance to commensal bacteria and foods.

Butyrate levels determine whether these two seemingly competing needs can be achieved.

High levels of butyrate:

  • Assist the immune cells in mounting a response to bacteria, viruses, and even cancer,
  • Improve oral tolerance of foods,
  • Increase the number of immune cells that suppress inflammation and allergic responses,
  • Enhance the anti-bacterial activity of macrophages to restrict pathogen growth,
  • Suppress mast-cell activation, and
  • Co-ordinate the mast-cell and immune system to both promotes immunity and immune tolerance.

     

Without sufficient butyrate, Th2 dominance, autoimmunity, and mast-cell activation are inevitable. 

 

ENERGY METABOLISM

Butyrate is an energy source, not only for the gut, for the remainder of the body, and it also regulates energy homeostasis throughout the body.

Butyrate is the primary energy source for the intestines, which consume up to 95% of butyrate.

Butyrate then enters the liver and fat tissues, where it regulates whole-body energy homeostasis. 

High levels of butyrate result in metabolic programming. Butyrate;

  • Prevents obesity by increasing energy expenditure,
  • Improves blood glucose and insulin,
  • Regulates appetite and leptin,
  • Improves triglycerides,
  • Prevents fatty liver, and
  • Improves mitochondrial function.

 

Interestingly, aside from being produced by bacterial fermentation, butyrate can also be produced in smaller amounts by our cells through fatty acid oxidation itself.

Without sufficient butyrate, energy dis-homeostasis is inevitable, resulting in obesity, metabolic syndrome, fatty liver, and mitochondrial issues. 

BRAIN FUNCTION

The brain is a site of immense energy demands.

Butyrate not only crosses the blood-brain-barrier, but there are SCFA transporters and receptors in the brain.

While research is still emerging, studies to date all point to butyrate playing a significant role in both the brain and the gut-brain-axis. 

High levels of butyrate;

  • Maintain the blood-brain-barrier – similar to the intestinal barrier,
  • Have an anti-inflammatory effect on the brain,
  • Facilitates neuronal plasticity by transforming short-term memory into long-term memory,
  • Restore neuronal plasticity as a result of illicit drug use (including cocaine or amphetamines) and I suspect pharmaceutical drug acquired brain injuries,
  • Increase GABA (an important inhibitory neurotransmitter that puts the brakes on histamine in the brain),
  • Regulate the hypothalamic-pituitary-adrenal (HPA) by reducing cortisol in response to acute psychological stress, and
  • Stimulate colonic motility by stimulating serotonin secretion from the gut cells through activation of the vagus nerve.


All of these points to butyrate play an essential role in providing the energy the brain needs to maintain homeostasis in the brain and communicate with the gut-brain-axis.

MECHANISM OF ACTION

 

 

The mechanism of action of butyrate is still emerging.

However, the degree of the interface between butyrate and the body is truly astounding.

Fundamental mechanisms of action include:

  • Microbiome homeostasis - Butyrate appears to play a vital role in regulating the gut-biome, which produces many essential vitamins and neurotransmitters needed for health.

  • Histone activation - Butyrate activates the HDAC genes that promote survival, plasticity, and cell regeneration and protect cells from oxidative stress. This accounts for much of its mast-cell stabilizing properties.

  • G protein-coupled receptors (GPCR) - Butyrate regulates energy homeostasis via GPCRs.  GPCRs bind extracellular signals such as light, hormones, and neurotransmitters that influence cell function. GPCRs are critical to homeostasis, the immune system, the autonomic nervous system, and energy production.

  • Mitochondrial activity - Butyrate regulates energy homeostasis in the mitochondria. Mitochondria are responsible for generating the energy (ATP) needed to power the cell's biochemical reactions. 

Simply put, there are few genes, cells, and functions not regulated by butyrate levels. 

HOW TO INCREASE BUTYRATE

Fortunately, there are many ways to increase the levels of butyrate with foods, fibers, probiotics, and direct supplementation.
 

FOODS HIGH IN BUTYRATE

Butyrate is also produced in an animal's gut and transferred via its milk.

Butyrate occurs naturally in whole cow's milk, butter, ghee, cheese (especially goat's cheese), and human breast milk.
 

FOODS THAT FEED BUTYRATE-PRODUCING BACTERIA

Most whole grains, fruit, and vegetables have prebiotic fibers to some extent. 

However, foods that particularly feed butyrate-producing bacteria include:

  • Jerusalem artichokes
  • Yacon tubers
  • Burdock roots
  • Chicory roots
  • Dandelion roots
  • Garlic
  • Onions
  • Leeks
  • Asparagus
  • Globe artichokes
  • Legumes
  • Brassica family
  • Fresh beans
  • Beetroot
  • Sunflower seeds
  • Pumpkin seeds (pepitas)
  • LSA

 

PREBIOTICS

Prebiotics are food supplements that produce butyrate in the gut through microbial fermentation.

Hyper producers of butyrate are:

  • Fructose Oligosaccharides (FOS)
  • Galactose Oligosaccharides (GOS)
  • Xylooligosaccharides (XOS)
  • Disaccharides (Lactulose)
  • Potato Starch (and RS2)
  • βeta-glucans
     

The products with this prebiotics are:

  • MegaPre
  • Zinobiotic (this is not available in Australia - but can be purchased overseas. It is a practitioner-only product; however, you can use my name).
  • Actilax (this is available in Australia without a prescription)

I use all three and rotate them as they feed different bacteria. Zinobiotic is not suitable for individuals with small intestinal overgrowths.

 

PROBIOTICS

There has been limited research undertaken into probiotics that cross-feed with butyrate-producing bacteria.

Lactobacillus Rhammnos GG is one probiotic. 

However, MegaSporeBiotic, when combined with MegaPre, produced a 150% increase in butyrate production in clinical studies. That is, together they had a synergistic effect due to the cross-feeding with the whole microbiome. 

As MegaSporeBiotic is a quorum-sensing probiotic that restores homeostasis to the microbiome it is my preferred probiotic for increasing butyrate. 

 

BUTYRATE SUPPLEMENTATION

Most studies that supplement butyrate directly use sodium butyrate.

There are a plethora of new types of butyrate supplements that have come onto the market. Most marketing materials quote improved bioavailability.

It is important to emphasize that sodium butyrate supplementation will not directly raise butyrate-producing gut bacteria levels. It will simply protect cells from the impact of low butyrate production by the microbiome. 

The dosages of sodium butyrate used in the studies vary widely. Studies use doses of between 100 - 1200 mg/kg. Studies also use them via enemas direct to the colon. Pessaries can also likely be used. If you are using other forms with higher bioavailability the dosage will of course vary. 

It is important to note that high doses can activate the HPA axis, becoming a stressor, such that it is best to titrate any supplementation. Also, developing brains both whilst pregnant and in children should not be exposed.

CONCLUSION

In conclusion, SCFA receptors are important regulators of mast-cell and immune function, including neuroinflammation, host energy metabolism, and homeostasis.

There is no commercially available way of measuring butyrate levels. 

However, butyrate-producing bacteria, and the firmicutes family, are measured by most complete microbiome mapping tests. 

As a general rule butyrate producers should be 25% or more of the microbiome. The higher the inflammation in the body the higher we want butyrate producers.  

Whilst demand for butyrate can be inferred from a range of standard blood panel markers including metabolic markers (such as blood glucose, insulin, and triglycerides) and inflammation (raised CRP). 

Butyrate levels are amongst the most important markers of health and the ultimate mast-cell stabilizer.  

 

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