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Wendy McLean (00:06):
Welcome to Common Ground, a podcast series discussing new research and interesting projects in the field of complementary medicine. Hello, my name is Wendy McLean educator at vital.ly.
Vital.ly is a digital platform, a professional health resource, and a distribution service all in one.
Firstly, I'd like to begin by acknowledging the Gadigal people of the Eora nation as the traditional custodians on the land, on which we gather here. I'd also like to pay my respect to the elders, both past and present.
When it comes to human health the intestinal barrier is of critical importance. This barrier is the most extensive and crucial mucosal surface of the body, forming a protective barrier against the external environment, which contains not only nutrients, but also potentially harmful microorganisms and toxins. So the challenge is to allow efficient transport of nutrients across this mucosal surface while excluding the passage of harmful molecules and microorganisms.
A wide range of chronic inflammatory and autoimmune diseases have been linked to reduced intestinal barrier integrity, or that is, enhanced intestinal permeability, and this is sometimes also referred to as leaky gut. However, despite the immense interest in gut permeability and its pathogenesis over the last two decades, much remains unknown.
Today on Common Ground naturopath Brooke Schiller shares the latest research on intestinal barrier health, as well as clinical insights on the testing and therapeutic interventions for improving and maintaining the integrity of the intestinal barrier.
Brooke is a degree-qualified naturopath and nutritionist based in Sydney with a passion for digestive health. Brooke follows an evidence-based approach and has a deep love of learning. Her own health journey led her to the herbal medicine path, and now her greatest pleasure and number one driver is guiding people to better health.
Welcome to Common Ground Brooke
Brooke Schiller (02:06):
Thanks for having me, Wendy. I'm thrilled to be here.
Wendy McLean (02:09):
So Brooke, could you explain to us what is the intestinal barrier and what exactly is intestinal permeability?
Brooke Schiller (02:18):
Absolutely. So the intestinal barrier is part of the gastrointestinal tract that allows the absorption of nutrients and fluids, while limiting the transport of potentially harmful antigens and microorganisms from passing through the intestinal epithelium to the underlying tissue.
There is a delicate balance to keep a functional barrier and it's maintained by physical defense mechanisms, including tight junctional complexes that link the epithelial cells and as well, the mucosal surface of the epithelial cell lining.
So intestinal permeability, this is describing the control of material passing from inside the gastrointestinal tract through these cells lining the gut wall. It's a necessary function, but the issue arises when we get impaired or increased intestinal permeability. So impaired impermeability occurs when the intracellular proteins holding these tight junctions together disassemble and this results in translocation of luminal contents to the inner layers of the intestinal wall, which can trigger local or systemic inflammation and disease. Generally, we can have permeability of the stomach lining, the large intestine, or the whole gastrointestinal tract, but generally we're referring to the small intestine and a lot of research is focused on small intestinal permeability. So throughout today, when I refer to intestinal permeability, I do mean impaired or increased permeability.
Wendy McLean (03:58):
Right, that's really interesting, Brooke. I don't know if everyone would be aware that we could have permeability of the entire intestinal tract and that when we're talking about it, we're mainly talking about the small intestine. So thanks for clarifying that. And I think also that was a good explanation, because some people might have this idea that intestinal permeability there's actual holes in the lining. So that's a great, great clearing up of that. So what actually causes intestinal permeability?
Brooke Schiller (04:30):
Yeah. So because the intestinal barrier is highly responsive, there are many factors that can alter its permeability. Some are microbiota modifications, mucus layer alterations, and epithelial damage. And so what causes these, these big things, are genetic factors, so things like coeliac disease; environmental factors, such as drug or antibiotic intake; infections; lifestyle patterns; and even migration to a different location can affect the permeability.
Wendy McLean
Wow. That's very interesting.
Brooke Schiller
It really is. Yeah. and then lastly, dietary factors like alcohol and Western style diets.
Wendy McLean (05:20):
Right, okay. So there are many things that can contribute to it. And so what are the indicators for intestinal permeability?
Brooke Schiller (05:28):
I think this one's quite interesting because not only should we look to gastrointestinal markers such as bloating and abdominal pain, there are a number of other indicators of permeability that we should look out for. And first and foremost is long-term consumption of a Western style diet. So if a client comes to you and they have been eating a typical Western diet for their whole life, intestinal permeability is something to think about. Likewise alcohol, non-steroidal anti-inflammatory drugs, and also high emulsifiers in the diet can contribute. Inflammation is a big one and bacterial overgrowth. So if someone has SIBO or dysbiosis of some description, permeability is something to think about. And then lastly, metabolic markers. So obesity is a risk factor. So if someone comes to you with obesity or dyslipidemia, insulin resistance, hyperglycemia, intestinal permeability is something to consider.
Wendy McLean (06:40):
Right, so a lot of factors there. So we would definitely need to take a very detailed case assessment of an individual.
Brooke Schiller (06:48):
Absolutely, absolutely.
Wendy McLean (06:50):
So what are some of the health conditions? I mentioned that there's a range of inflammatory and autoimmune conditions, but what are these conditions associated with intestinal permeability?
Brooke Schiller (07:01):
Yes. Well, at this stage, the scientific community hasn't yet determined whether the loss of barrier integrity is the cause or the consequence of these diseases. So it's quite an interesting double edged sword there, but some of the conditions to think about are gastrointestinal. So we have inflammatory bowel disease, coeliac disease, gluten sensitivity, and IBS. I touched on it above, but metabolic conditions such as diabetes type two, and also non-alcoholic fatty liver disease. And then some autoimmune states that are in the research include HIV and Parkinson's and lastly some mood disorders, so major depressive disorder, and autism spectrum disorder.
Wendy McLean (07:52):
Definitely a whole range of things. But yeah, as you say, is it a chicken or egg situation. So probably a perpetuating cycle.
Brooke Schiller
Yeah, I think so.
Wendy McLean
So how do we test for intestinal permeability and how accurate are these tests?
Brooke Schiller (08:11):
So there are a range of tests that are available and currently the lactulose/mannitol challenge and urine recovery, I believe is the best test that we have for intestinal permeability. This is a test where clients drink a lactulose/mannitol solution and then do a six hour urine collection. So the way it works is that the probe sugars are passively absorbed from the intestine rather than extensively metabolised. And because of this they're excreted unchanged in the urine in proportion to the quantities absorbed. So an elevated flux of lactulose will generate an increased ratio between lactulose and mannitol. And this is a sign of loss of intestinal barrier integrity, but it's not without its limitations. So at this stage, there's been a couple of studies looking at the length of collection time and both indicate a shorter time would be beneficial. Although at this stage, the six hour collection time still remains in commonly available tests.
Next test we have is serum zonulin. So during the last decade, there was a big push to find a reliable biomarker, able to assess intestinal permeability in the blood. And one of the first proteins identified with promising results was zonulin. So zonulin is a protein that's capable of reversible tight junction disassembly, and therefore it was implicated in the regulation of mucosal permeability. What we need to remember is zonulin is part of a normal protective response in the body. Among several potential substances that can stimulate zonulin release is exposure to large amounts of bacteria. So for example, a bacterial overgrowth and also gluten. So there've been identified as two of the most powerful triggers for zonulin release. Once the pathogen is gone, zonulin levels drop and the junctions close.
So although serum zonulin held a lot of promise, it's not holding up in the research as being a consistent or reputable marker. And part of the problem here is that zonulin is not only produced by enterocytes. It's created by many tissues and organs, including adipose tissue, the liver, the brain, the heart, immune cells, lungs, kidneys, and the skin. So this likely explains why no correlation has been found between serum and faecal zonulin at this state.
Brooke Schiller (10:58):
Yeah. So then we look to faecal zonulin as the next obvious marker. And unfortunately this hasn't shown to be reliable yet and is getting mixed results in the research. But aside from that, we do need to remember that not everyone can make zonulin. So about 17 to 20% of people don't have the gene profile. Zonulin is the precursor to Haptoglobin 2. And some people don't make this, they make haptoglobin 1 instead. So testing zonulin for them, which would, would show as negative, which isn't correct.
Wendy McLean
Right. That's really interesting.
Brooke Schiller
Yeah. A really good one to remember when we think about zonulin. While in some studies, faecal zonulin is showing to be beneficial. It's just not consistent at this stage.
Wendy McLean (11:50):
Right.
Brooke Schiller (11:53):
Faecal calprotectin is another one that's used most commonly in IBD, inflammatory bowel disease. And although it is effective as an inflammation biomarker, it's not fully representing gut mucosal function. So there can be barrier defects, independent of any intestinal inflammation. So they're the main ones to discuss.
There are a couple of markers emerging as potential markers of intestinal barrier dysfunction, and two of those Intestinal Fatty Acid Binding Proteins and plasma lipopolysaccharide binding proteins. But at this stage I think we need to consider the weight of the research when there's new tests are coming out and seeing what's actually working consistently.
Wendy McLean (12:42):
Yeah, absolutely. So it looks like at this stage, we don't really have a gold standard test. You know, the lactulose/mannitol test, but you’re talking about the urine testing times there. So would it be fair to say that as a practitioner, you would use multiple methods and look for multiple signs and symptoms when assessing intestinal permeability?
Brooke Schiller (13:07):
Yes, absolutely. I think we always need to take the test results alongside a client's presenting symptoms. So certainly lactulose/mannitol is the best we have, but we do need to consider all the case taking evidence yet. They're absolutely.
Wendy McLean (13:22):
Yeah. And so it, once we've worked out or suspect intestinal permeability, how do we actually go about helping someone with it?
Brooke Schiller (13:32):
Great question. At this stage, deficiencies of vitamin D, vitamin A and zinc have been found to compromise the epithelial barrier with an increased risk to infection and inflammation. So a key goal is to assess the deficiencies of these and bring these nutrients into range. So that's number one. I think many people would have heard of glutamine and that is very commonly used in the research for intestinal permeability. Multiple lines of evidence have indicated that this modulates the expression of tight junction proteins and the dose in the research varies between 15 to 30 grams per day. So I think it's a good one to highlight because there are a number of products on the market, which contain much less than this. It needs to be considered, whether we're giving that therapeutic dose.
Wendy McLean (14:31):
Wow. Yeah. That's, that's a high a dose, certainly in the research. And what about, what about probiotics Brooke? I read that there were some specific strains that might be helpful.
Brooke Schiller (14:44):
Yeah. Probiotics. Absolutely. So two strains that are in the research are lactobacillus rhamnosus GG. So LGG. Studies have shown that this significantly reduces that increased gut permeability. And then the other one is Saccharomyces boulardii. It's well-researched and it's been shown to directly restore intestinal integrity, as well as inhibit pathogenic bacteria that can affect the integrity of the gut barrier too. So it works if by dual function.
Wendy McLean (15:22):
And dietary interventions, I'm sure.
Brooke Schiller (15:27):
Always. Dietary interventions have a big role to play. And number one is one of my favorites, fibre. So dietary fibers are really relevant in the modulation of inflammation and may influence the gut barrier via short chain fatty acid production. So changes in dietary fibre intake can also affect the composition of the microbiome. And what's getting a lot of interest in the research is Akkermansia. So Akkermansia is a mucin degrading bacteria and it resides in the intestinal mucus layer. Its presence has shown to be crucial for the integrity of the epithelium, but in the absence of dietary fibre, Akkermansia actually utilises the host mucus glycans as its nutrient source. And this can lead to alterations of the colonic mucus barrier. So fibre is a massive one.
Wendy McLean (16:27):
Yeah. And that, it's huge because I think that only about a quarter of Australian adults are actually meeting their daily dietary fibre intakes.
Brooke Schiller (16:39):
Really? That is a fascinating statistic. It doesn't surprise me. I think another really interesting dietary factor is polyphenols. And specifically I was looking at some research on flavonoids recently and they have also shown to have beneficial effects on the epithelial barrier. So the normal intake of flavonoids in the population is thought to be below the threshold for significant beneficial effects. So this would indicate we may need to supplement in addition to the normal diet for susceptible individuals. And again, many studies have indicated that these flavonoids not only protect the barrier integrity by acting on the tight junctions, but they can also modulate the gut microbiota. And an example was in a study that looked at flavonoid rich cranberry extract, and this increased the proportion of Akkermansia in one trial.
Wendy McLean (17:39):
Right.
Brooke Schiller (17:41):
So fibre and polyphenols are two to definitely think about. And I can't not talk gluten. So I did mention earlier that gluten triggers zonulin release. And the zonulin response is theorised to be a protective mechanism to the intestinal permeability. So we have to remember that even a high bacterial count irrespective of its species will trigger an elevated zonulin release in the intestine. Haptoglobin two and zonulin are key in the inflammatory process. So just because gluten causes a rise in zonulin, it doesn't necessarily mean this is above the normal protective mechanism.
Wendy McLean (18:30):
Okay. So we don't necessarily all have to give up gluten?
Brooke Schiller (18:35):
Absolutely not. The research doesn't suggest that gluten needs to be eliminated for everyone. Certainly we'd look to coeliac people and make sure it was out of their diet, but the rest of the population, unless there's specific gluten sensitivity there, it's not indicated at this stage.
Wendy McLean (18:54):
And so are there any other things that we should avoid from or exclude from the diet?
Brooke Schiller (19:00):
Yes. Alcohol is one of the big ones. So studies do suggest that the effects of ethanol on the intestinal barrier have shown consistent increases in permeabilities in a range of different models. So that's a big one to think about with your clients, especially if they have that high alcohol consumption.
And then of interest I think is food additives. So lately there's been a lot of research into certain food additives which have been associated with intestinal barrier dysfunction, and two of them, I'm going to talk about are Carboxymethylcellulose, which is also known as E 466, and polysorbate-80, which is E 433. They are are two really commonly used additives in the food industry and you can recognise them on food labels by their E numbers. So there was an animal trial done with these additives and they were administered at relatively low concentrations, which was believed to be representative for humans when a lot of processed foods are daily consumed and they did induce a reduction of mucosal thickness as well as a higher contact of bacteria with the epithelium and low grade, low grade inflammation.
Wendy McLean (20:27):
Right. Well, that is very interesting. And what are some examples of the type of food that we would find these particular additives in?
Brooke Schiller (20:37):
Yeah, well E466. It's a multi-functional ingredient. It's use it as a thickness, binder, emulsifier and stabiliser. So this found in foods like chocolates, ice creams, condiments, and even instant pastas, anything that's looking for that smooth consistency. And then in E433 is also an emulsifier. So that's found in ice creams and sauces again, and this one helps water-based and oil-based ingredients mix together. So buying anything with those types of ingredients, you would assume that there's some kind of emulsifier in there.
And then two more, I've got is medications. So we need to think about the role of nonsteroidal anti-inflammatories because these are thought to cause a direct damage to the surface of the epithelium. Proton pump inhibitors are also in question, although at this stage, it's thought to have more of an indirect impact rather than impact on the barrier.
And last but not least is stress. And I think it's a really important one in the current climate because stress has been shown to increase intestinal permeability in animal models. And specifically the research attention is on exercise-induced stress because it's believed that this represents a combination of physical and psychological stress that can impact the barrier.
Wendy McLean (22:10):
I have been reading about the exercise-induced or potentially exercise-induced IP and I've read, I think it was, that exercise puts stress on the permeability at more than two hours at 60% of our VO2max of exercise. So that's more moderate to high intensity exercise. Would that be correct?
Brooke Schiller (22:35):
Yeah, absolutely. I've read a few studies on athletes actually, and it's definitely one to consider for athletes or anyone training at high intensity for higher length of time on a regular basis. And the reason they think this occurs is because prolonged exercise can increase core temperatures and this reduces the blood flow within the intestines. So that mechanism is thought to result in an increase in the intestinal permeability.
Wendy McLean (23:06):
Right, that's, that's really interesting. And I guess it's something to consider again, when you've got that patient sitting in front of you and assessing their case and looking at their, not just diet, but their lifestyle and exercise levels as well.
Brooke Schiller (23:22):
Absolutely. It's important to see the whole picture.
Wendy McLean (23:26):
So what are some of the key takeaways that you would like our listeners to remember from today Brooke? There have been so many good points.
Brooke Schiller (23:34):
It’s a big one, but I'll, I'll have three key takeaways, right? Mostly we need to remember that intestinal permeability is not only present in gastrointestinal disease. It's a risk for involvement when you see clients with metabolic conditions, autoimmunity, and mood related conditions as well.
Number two, the lactulose/mannitol our test is the best we have and it's actually reasonably affordable. So this enables testing before and after treatment to see that adequate permeability has been restored.
And then number three, I would say, consider the research of therapeutic nutrient dosages, and support with those dietary factors to improve the microbiome. We need to remember that gluten isn't always the bad guy. So they would be my three Wendy.
Wendy McLean (24:25):
That's great, Brooke. Three great points to sum up with, and thank you so much for your time today, Brooke. I certainly learned a couple of new things as well. So yeah, you've shared some great clinical insights on both the testing and treating for intestinal permeability. So thanks very much.
Brooke Schiller (24:44):
Thank you, Wendy. It's been such a pleasure to speak with you.
Wendy McLean (24:48):
To our listeners. Thank you. And please subscribe to Common Ground. We really appreciate your support and feel free to leave us a review. We'd absolutely love to hear from you. Thank you.
