I know it sounds like an alien planet or a character from Star Trek but this amazing protein is a fundamental part of gut health (although it is found elsewhere in the body), so I thought I should introduce you to it.

Our gut is one long tube and our intestines are about 8-9 metres in length and is a huge part of our immune system as it is a place where our outside environment meets up with our inside environment. One of the most important factors is the structure of our small intestine which has a tightly packed single layer of cells that interact and negotiate what is allowed across them and into our bloodstream. 

Imagine a tunnel, and along the walls of the tunnel are doors. If you got out of your car and knocked on one of the doors, a decision would be made as to whether you would be let in.  This is what we call ‘intestinal permeability’.  Decisions are made as to whether you are ‘friend’ (nutrient) or ‘foe’ (pollutant or ‘bug’). Of course, in reality it’s more complex than that.   We also have a 2 layers of mucus (the lovely slimy stuff) and specific immunity cells that police the border too. 

The ‘doors in our tunnel’ are what are known as tight junctions and they open and allow nutrients in or out and close to keep the ‘riff raff’ out.  You may have heard of the term ‘leaky gut’ which refers to these tight junctions opening permanently. The technical term is ‘intestinal hyperpermeability’. In reality there is no such thing as a leaky gut (like a leaky tap or bucket) its just a buzz term and easier to say than intestinal hyperpermeability which doesn’t exactly roll off the tongue!  Let’s be clear the tight junctions are meant to open and close – they open when we are stressed to ensure we have more nutrients and certain foods and drinks will also open or close them. Babies in particular are meant to have a ‘leaky gut’ so they can absorb all of the good stuff from breastmilk that would otherwise be too large to cross into the bloodstream from the gut. 

Back in 1993, Zonulin was discovered (I know you were wondering when the heck I was actually going to start discussing zonulin) and was found to be a key modulator for the opening and closing of these tight junctions. (1) 

Whilst there is still a lot we don’t know about ‘leaky gut’, there does appear to be an association with increased intestinal hyperpermeability and chronic disease (although not all chronic diseases have been linked to increased gut permeability) (1) especially when inflammation is driving the disease (this includes lung diseases and COVID 19).

What we do know is that higher levels of zonulin increase the loosening of these tight junctions (imagine those doors in that tunnel not closing shut properly) and thereby increasing the intestinal permeability of the gut lining. (2, 3)

 

Why does that matter?

Because if the intestinal lining is too permeable, then toxins and bugs (viruses and bacteria) and LPS (lipopolysaccharide), a fat-sugar based substance found on the wall of gram negative bacteria that is associated with inflammation, all are allowed to pass though and enter the bloodstream causing havoc in our bodies.  

Whilst many things can create this intestinal hyperpermeability (including medications such as ibuprofen (4) and other inflammatory markers such as IL-13 and TNF) (5), zonulin is an interesting one especially as food and stress can influence it.  

There appears to be 2 things that increases zonulin in people:

1. Bacteria (6) – an increase in zonulin has been noted with an increase in bacteria and yeasts, both those that cause disease and those that don’t, for example Salmonella and Candida.  It may be that this in fact a defense mechanism’. (6, 7) Dysbiosis (an imbalance in gut microbiota) can trigger an increase in zonulin which may then lead to ‘leaky gut’ which leads to inflammation which exacerbates the ‘leaky gut’ and so you have a vicious cycle. (8)
2. Gluten (mainly in those with celiac disease) although the research in healthy adults and those with non-celiac gluten sensitivity shows mixed results. We do know that gluten increases zonulin but it may only be a problem when the gluten is damaging the gut barrier at the same time. (8) 

Some other things may increase zonulin – herbs such as hops, sugar, coconut oil, dairy, inflammation, alcohol and stress. 

To be clear – having a permeable gut is natural, it’s a dynamic process whereby those tight junctions or doorways are continuously opening and closing – and food and stress will influence this. For example the alcohol in red wine opens those tight junctions and the polyphenols (the plant nutrients found in red wine actually close them). The problem is when there is severe, chronic inflammation or injury to the gut lining and those then don’t shut properly. Then you have a problem. 

Testing

There have been tests for zonulin but I’m not sure if there is value in this because – high amounts of zonulin isn’t necessarily a marker for intestinal hyperpermeability or inflammation and zonulin increases and decreases continuously.  Testing inflammatory markers or molecules that shouldn’t be absorbed like mannitol would be better.

Tips

• Prevent infection, inflammation and injury to the gut lining in the first place 
• Prevent or treat dysbiosis
• Possibly remove gluten and/ or address food intolerances. 

1. Eat fibre and prebiotic rich foods (lots of veggies, lots of colour, handful of berries everyday)
2. Eat fermented foods (Kimchi, sauerkraut, kefir, pickled veg, kombucha, yoghurt, miso, tempeh, sourdough bread, a little cheese if you tolerate it) or take a probiotic supplement. A meta analysis recently showed that when this is a long term practice, better results are seen. 
3. Mediterranean type diet would be idea (whole foods where possible, olive oil and other healthy fats, lots of veg and fruit with a little meat on the side, handful of nuts and seeds, legumes and lentils) 
4. Try gluten free grains instead – if you have celiac’s disease then take it seriously and do not eat gluten containing foods even if you don’t have symptoms.  
5. Make sure you drink enough water during the day
6. Vitamins A and D
7. Find ways to manage stress (if you are female it’s even more important the 2nd half of your cycle when cortisol increases naturally).  (9-11)

 

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996528/
2. https://pubmed.ncbi.nlm.nih.gov/22731712/
3. https://pubmed.ncbi.nlm.nih.gov/21248165/
4. https://pubmed.ncbi.nlm.nih.gov/19148789/
5. https://pubmed.ncbi.nlm.nih.gov/20177070/
6. https://pubmed.ncbi.nlm.nih.gov/12404235/ 
7. https://pubmed.ncbi.nlm.nih.gov/25734566/
8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8583036/
9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7548501/
10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706658/
11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4878258/

 

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