Stop Leaky Gut ... with Polyphenols

Broad Benefits from Berries plus ...

Leaky Gut - often talked about but not well understood and certainly with few studies actually measure gut permeability within the context of the discussion. Nevertheless, it is an important metric for health as it assesses the integrity of the gut barrier.

Why does there need to be a barrier? Well there is a lot going on in the lumen of the gastrointestinal tract. Food is being digested and we do not rampant allergies from proteins or peptides getting across into the blood. Digestive processes (proteolytic enzymes, bile for emulsifying fats, breakdown of carbohydrates into the individual saccharides, are all events that you want isolated from the rest of the body. Then of course there is the microbiome, our partners in health. They play such an important part but then again, we cannot accept bacteria, yeasts and viruses circulating systemically in the body. Indeed, normally at least 70% the immune system lines the gut to make sure that everyone knows their place, does their job and does not accidentally cause havoc.

Here is the challenge. We need to keep the lining of the gut solid, with a tight barrier, when we know that the cells have to be replaced at a steady rate given the nature of the flow related breakdown of the barrier. The barrier needs to be selective, we need to let water pass through for hydration and selected, important nutrients. Specialized transport systems need to be operational to transport specific nutrients - vitamins, charged elements like polyphenols and let’s not forget amino acids. Fats are allowed in through spherical bodies (liposomes) that generally enter into the lymphatics and then eventually into the blood stream.

The liver is a major controller as well. Beyond the source of bile for fat metabolism, the liver acts like a quartermaster, the Supply Chain in Chief. Glucose, amino acids, fats are often stored there and then distributed to the body as the needs arise. A giant warehouse that also serves as a detox center where it tags “rubbish molecules” for disposal with additions of molecular tags like glutathione.

It is great when the system works as planned, but conditions arise when the gut barrier is compromised. It could be the result of toxic chemicals that have been ingested, disturbed pH, bacteria that produce toxins that kill the epithelial cells (directly or indirectly through an activated immune system), or other microbial bad actors.

The barrier can breakdown in two dominant ways. The connections between epithelial cells can be loosened. These connections are called tight junctions, pretty self explanatory there. Only very small molecules can pass between these junctions … unless the proteins that pull on the tethers become compromised. Then the space between cells widens and stuff that should not get through starts to get pass the barrier.

The other way to compromise the barrier is to cause frank death of epithelial cells. Inflammation, toxins, xenobiotics all take a toll in the cells. The gut is very rapid in wound repair and epithelial cells replicate and migrate rapidly to cover the wound. If the problem is persistent then the structure of the gut mucosa may become simplified, less complex but that comes at a cost of reduced digestive capacity. Inflammatory bowel disease is a classic example of this.

Some years back I was measuring gut epithelial permeability in response to a unique class of mediators that I was pioneering - Histamine Chloramines - Leaky Gut caused by Histamine Chloramines.

These are potent oxidants that also retain their ability to activate histamine receptors and so they contribute to gut inflammation and allergy (Histamine Chloramines and Exptl Gut Inflammation). There are lots of mast cells in the gut that produce histamine. They are innervated (connected via nerves to the brain) and help tell you that your tummy is upset, stop what you are doing as we have trouble down here. Histamine chloramines are readily formed when histamine reacts with bleach, which is made from white blood cells that fight infections. Yes, your neutrophils make bleach in vast amounts, and the enzyme that makes it (myeloperoxidase) is green in color and is the reason why pus is green.

Polyphenols & Barrier Function: Clinical Evidence

With this background primer we can now address a recent large clinical trial that assessed if dietary polyphenols have any impact on the epithelial barrier function. Seniors, Leaky Gut & Polyphenols They measured the integrity of the barrier, and if it was “leaky” or not, by measuring serum levels of zonulin, which is a key protein that acts as one of the tethers that tighten the Tight Junctions that determines the size of the gaps between epithelial cells. High levels of serum zonulin indicates that the gut is becoming leaky. A successful therapy or intervention will lower serum zonulin levels as it tightens up the barrier.

In this study, a;; participants were over the age 60 years of age, so it was an older population as these tend to have issues with gut barrier function. They were randomized into a LOW or a HIGH polyphenol diet for 8 weeks in a Cross-Over design. That means that each participant took each diet, after 8 weeks they transferred over to the other diet. This design structure is statistically quite powerful as it allows for each individual to be their own control. With this design 51 subjects completed the trial and with excellent compliance (they did what they were told).

KEY OUTCOMES

The key outcomes were diverse:

• There was a dramatic & significant reduction in serum zonulin with the HIGH polyphenol diet. This was also time dependent, with improvements in barrier function the longer they were on the diet.

• These actions were more pronounced in those with higher BMI’s (obese/overweight) and insulin resistance at the start of the trial.

• Blood pressure was reduced, more so in this not currently taking antihypertensive drugs.

• Both diastolic (when the heart is relaxed) and systolic (when the heart contracts) BP was reduced in women.

• The gut microbiome was altered by high polyphenol diets. In particular bacterial species that ferment fiber into butyrate were enhanced (Ruminococcaceae and Faecalibacterium).

CONCLUSIONS

A diet that is rich in polyphenols (think of color - berries, fruit, vegetables with color) has dramatic health benefits. It not only provides the drive for a better gut microbiome, which in turn can impact the barrier function of the gut, but it also has systemic benefits. Here blood pressure was reduced. The most noticeable benefits were seen in those with inherent problems - overweight, insulin resistance - as well as high baseline LEAKY GUT.

Your diet has a huge impact on your health, here I hope that I have provided some solid science explaining why that is true. Bon appetit … just make it colorful and spicy.