What To Do About A Leaky Gut – Best Biohack Strategy

The Vitamin Clerk dives into a little biology for biohacking a leaky gut.  Part 2 of 2 blog series.

 

Visit Part 1 of this blog

 

The anatomy of the intestinal barrier begins with the layer of cells called enterocytes (and colonocytes in the colon) that face the inside of your gut.  Enterocytes have five types of barriers.  The Tight Junction is the barrier type of importance to permeability disorders.  It is a belt of filament proteins called actinomyosin found towards the top of the cells.

Along this belt, imagine several “buckles”.  They are made of proteins called Zonula Occludens and other types of proteins.  These buckles join buckles of adjacent enterocytes so tightly that they preclude the passing of even ions between the cells.

Another protein called Myosin Light Chain Kinase (MLCK) regulates this belt.  MLCK causes the filaments to tighten, thereby pulling open the “buckles” of the Zonula Occludens.  Many cellular signals regulate tight junctions by either activating or inhibiting MLCK or the Zonula Occludens.

 

 

How are tight junctions regulated.  We know more about tight junction regulation thanks to Vibrio cholera. 

 

This is the pathogenic bacteria whose toxin causes cholera diarrhea.  The toxin disassembles the Zonula Occludens of the tight junction buckles.  Turns out that mammals make a protein called Zonulin that is very similar to the cholera toxin.  Zonulin also loosens the Zonula Occludens of the Tight Junctions. 

The cellular signaling leading to the production of Zonulin is the mechanism by which our body regulates the permeability of the tight junction.

Gluten intolerance is the result of increased Zonulin production and prolonged permeability of the gut from steady state.  Gluten is made of subunits called Gliadin.  Gliadin binds to specific proteins on the surface of the enterocytes which signal the release and production of Zonulin.  This happens to everyone, but some with a genetic predisposition end up with a strong inflammatory reaction.

And remember, as I mentioned in Part 1, that the inflammatory response is caused by lipopolysaccharides (LPS) produced by bacteria in your gut.  Prolonged leaky gut leads to increasing presence of LPS throughout your body.

 

 

But when does it become a problem?  

So many factors cause a transient leaky gut and LPS mediated inflammation, including stress and exercise.  This is within norm.  Afterall, the tight junction is a dynamic interface that connects the gut, brain and immune system.  The delineation between being normal versus becoming a disease is believed to be established by Toll-like receptors (TLR’s).  TLR’s are found throughout your body.  They recognize foreign antigens, especially LPS, and turn on the pro-inflammatory response that facilitates the immune reaction.  When LPS activates TLR’s beyond a threshold, the inflammation may become persistent and lead to other diseases.

 

 How can we biohack the leaky gut problem?

The connection between intestinal permeability and health is very strong.  However, we need more clinical research before we can claim that treating dysregulation of intestinal permeability will reverse quality-of-life morbidities.  But we can certainly leverage functional food supplements as a preventative strategy. 

We want to focus on functional foods that promote less LPS exposure and more factors that upregulate the intestinal barrier.  Functional foods along with diet choices may give us a better chance at preventing health issues as we age. 

  

Here I suggest a biohack that promotes good gut health against a leaky gut.

1. Check if your L-Glutamine levels are low. Glutamine is an important amino acid for a healthy gut in multiple ways.

Our intestines consume more glutamine than other organs.  Enterocytes have high metabolic requirements because intestinal wall turnover new enterocytes every few days.  Glutamine is an important intermediate in energy metabolism for enterocytes.  Glutamine is a precursor to DNA and RNA.  It signals cell proliferation, particularly in injured tissues.  And it protects cells from oxygen free radicals.  It is the precursor to Glutathione, which is our body’s most important antioxidant.   

Glutamine also preserves intestinal permeability.  A cell-signaling enzyme called PI3K (Phosphatidylinositol-3-kinase) can increase intestinal permeability.  But Glutamine suppresses the presence of PI3K.  If Glutamine deficiency is a problem, you may not have enough glutamine to help you maintain a well regulated intestinal barrier.

We offer L-Glutamine in pure powder form, no fillers.  Consider taking at least 2,000 mg per day of L-Glutamine. 

 

2. Promote a balanced intestinal microbiome in favor of butyrate-producing bacteria.

Butyrate, acetate and propionate are Short Chain Fatty Acids (SCFA’s).   Our gut bacteria make SCFA’s from the fermentative breakdown of the fiber that we can’t digest.  But Butyrate is an important health-promoting molecule.

First, the cells of our intestinal wall --- particularly in the colon --- rely on butyrate just as much as glutamate for cellular energy production.  Second, butyrate also regulates the maintenance of our intestinal barrier.  Butyrate activates a cell-signal protein called AMP-Activated Protein Knase (AMPK).  AMPK inhibits the Myosin Light Chain Kinase (MLCK).  It maintains the filament proteins of the Tight Junctions in their normal conformation and keeps them less permeable. 

Butyrate supplements exist.  But that may be like patching the problem.  In the long term, consider consuming more fermentable fiber and functional foods that promote growth of bacteria that produce butyrate.  Foods that stimulate the formation of butyrate are resistant starches, arabinoxylan-rich whole grains, and brans from cereals such as wheat, rye and oats.  

 

Chaga mushroom is particularly interesting in this regard.  In models of diabetes, the unique polysaccharides from chaga have shown to influence the composition of the gut microbiota.

Our gut microbiota is 90% composed of two Phyla of bacteria --- Firmicutes (F) and Bacteroidetes (B).  The ratio of F-to-B is indicative of intestinal permeability.  The F bacteria produce butyrate.  The B bacteria are the type that produce LPS that can stimulate an inflammatory response.  Analysis of Type 2 diabetics have shown consistently that they have lower ratio of F to B, higher intestinal permeability, and chronic low-grade inflammation.

Chaga mushrooms apparently may reestablish a favorable balance of F-to-B bacteria.  This has been shown in traditional mouse models of diabetes.  Also, polysaccharide extracts upregulate the production of Tight Junction proteins.

I suggest Chaga mushrooms because of the high value as a functional food for your investment.  They are rich in other polyphenols and beta-glucans.  They promote healthy immune response.  Plus, they have a high antioxidative capacity.  Our Birch Chaga Powder contains Humic and Fumic Acids which promote detoxification throughout the body.

 

 

 

Follow these references if you enjoy reading the science behind the research on intestinal permeability.

• Bach Knudsen, K. E., et al. (2018). Impact of Diet-Modulated Butyrate Production on Intestinal Barrier Function and Inflammation. Nutrients, 10(10), 1499. https://doi.org/10.3390/nu10101499
• Ye, X., et al. (2023). Methanol extract of Inonotus obliquus improves type 2 diabetes mellitus through modifying intestinal flora. Frontiers in endocrinology, 13, 1103972. https://doi.org/10.3389/fendo.2022.1103972
• McCarty, M. F., & Lerner, A. (2021). Perspective: Prospects for Nutraceutical Support of Intestinal Barrier Function. Advances in nutrition (Bethesda, Md.), 12(2), 316–324. https://doi.org/10.1093/advances/nmaa139
• Wood Heickman, L. K., DeBoer, M. D., & Fasano, A. (2020). Zonulin as a potential putative biomarker of risk for shared type 1 diabetes and celiac disease autoimmunity. Diabetes/metabolism research and reviews, 36(5), e3309. https://doi.org/10.1002/dmrr.3309
• Perna, S., et al. (2019). The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review. International journal of molecular sciences, 20(20), 5232. https://doi.org/10.3390/ijms20205232
• Li, N., & Neu, J. (2009). Glutamine deprivation alters intestinal tight junctions via a PI3-K/Akt mediated pathway in Caco-2 cells. The Journal of nutrition, 139(4), 710–714. https://doi.org/10.3945/jn.108.101485
• Stojanov, S., Berlec, A., & Štrukelj, B. (2020).  The Influence of Probiotics on the Firmicutes/Bacteroidetes Ratio in the Treatment of Obesity and Inflammatory Bowel disease. Microorganisms, 8(11), 1715. https://doi.org/10.3390/microorganisms8111715