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How To Tell If You Have A Leaky Gut


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The intestinal barrier plays a critical role human health and disease. It allows for the absorption of nutrients from the food we eat, while at the same time, it protects against the entry of allergens, as well as bacteria, fungi, and parasites. Essentially, it plays the role of a gatekeeper. When this barrier malfunctions, it can cause allergies and autoimmune disorders. This is a condition we call “leaky gut.” But how do you know if you have it? Read on to find out.

Revolution Health Radio podcast, Chris Kresser

In this episode:

04:48 The basics of intestinal permeability
06:52 Is it a good idea to test for leaky gut?
09:34 Testing options for intestinal permeability
11: 50 The lactulose/mannitol test
15:59 The antigenic permeability screen

Chris Kresser: Hey everybody, it’s Chris Kresser here, welcome to another episode of Revolution Health Radio. And we are going to switch things up a little bit. If you’ve been listening to this show for a while, you’ll know that I have cycled through a few different formats over the years. Initially I did single-topic episodes where we dive deep on a particular topic, then I did some Q&A shows where I would answer multiple questions from listeners. I’ve always done some interviews, and that’s of course what I’ve focused on over the past several months. It’s been almost exclusively an interview show. And I am going to now do some Q&As again.

In this case, we’ll just be answering one question per show. We’re going to continue with the interviews because I think those are really informative and I get a lot of great feedback about them, and I enjoy doing them myself. But we’re going to intersperse some Q&A episodes as well, at least for the next few months. And who knows what comes after that.

But let’s start with a question from Kent and let’s give a listen and I’ll come back and answer it.

Kent Langley: Hello, this is Kent Langley and I’m calling on behalf of some friends and family. I’ve read a lot of your articles over the years and listen to most of your podcasts. Thank you for the fine work. The question I have is really relatively simple, but I suspect that it doesn’t have a simple answer. Is there a direct and high-accuracy methodology for testing if you have a leaky gut? My online research hasn’t turned up much, and I thought I would ask. If the answer is no, could you please explain why? Thank you.

Chris Kresser: Okay, thanks again, Kent. That’s a really good question. It’s one that we get in various forms quite often and it’s something I’ve been talking about a lot lately in my clinician training program. I’d love to cover some of the highlights at least briefly in the show.

The Basics of Intestinal Permeability

So before we dive into the nitty-gritty about testing for intestinal permeability, I just want to cover a few basics of what intestinal permeability is for those that aren’t as familiar with it, and then some general aspects about testing for this condition.

The intestinal barrier covers a surface area of about 400 m² and requires about 40 percent of the body’s energy expenditure, and that’s pretty remarkable when you consider that only 20 percent of the body’s energy expenditure is required by the brain. So this tells us that the gut barrier is really crucial. It plays an important role in human health and disease. It prevents against loss of water and electrolytes and the entry of antigens and microorganisms, so allergens, things that could provoke an immune response, as well as bacteria, fungi, parasites, things like that, it allows absorption of nutrients in the exchange of molecules between anything that we eat or put into our mouth and then the inside of our body.

Do you have leaky gut? Two tests to consider.

I think I’ve said this before, but if you really think about the gut, it’s essentially just a hollow tube that connects the mouth to the anus. And everything that is inside of the gut is technically outside of the body. It’s kind of hard to get your head around that, but it’s really the inside of the gut is not technically inside of the body. And in order for it to move in the body, anything that’s in the gut to move into the body has to cross that barrier. And that’s really what the barrier is there for, it’s, at a simple level, supposed to let in things that should get in and keep out things that shouldn’t, that should stay out. And when it’s working well, it does a good job of that. But when certain conditions are present, the barrier’s capability of doing that regulatory task breaks down, and then this is when all kinds of problems can happen.

So there are a lot of different things that can interfere with the gut, the function of the gut barrier. Diet is an obvious factor. Western inflammatory diet, lack of fermentable carbohydrates, and lack of fermented foods, infections and toxins, so bacterial, viral, parasitic infections, fungal overgrowth, heavy metals, mold, etc. Certain medications like proton pump inhibitors, antibiotics, or NSAIDs; lifestyle factors like chronic stress or sleep deprivation or inappropriate physical activity, like too little or too much; inadequate immune stimulation during our developmental period. This is known as the hygiene hypothesis. So hygiene and really clean environments have done a lot to reduce acute infections and saved a lot of lives in that process, but there’s a theory that these overly or these particularly sterilized environments have actually contributed to immune dysregulation because our immune systems aren’t properly stimulated when we grow up in those kinds of environments. Which explains why autoimmune diseases are really quite rare in the developing world when compared to the incidents in the developed world.

Then there are other factors which we call endogenous factors, which means they’re just things that are going on inside of the body that can contribute to leaky gut like chronic inflammation, or SIBO, or gut-brain axis problems, where low levels of certain hormones like melanocyte-stimulating hormone, or MSH, which regulates gut permeability, and then there’s actually probably some genetic susceptibility to leaky gut. For example, one study showed that 70 percent of asymptomatic relatives of patients with celiac disease were positive for intestinal permeability when they were screened. So there does seem to be a genetic component.

Is It a Good Idea to Test for Leaky Gut?

So before we talk about the different types of testing that are available for intestinal permeability, we should actually take a step back and talk about whether it’s even a good idea to test for intestinal permeability and when we should test for it. So my opinion is that intestinal permeability is almost always caused by something else that’s further upstream, meaning that it comes before intestinal permeability and it’s the underlying cause of intestinal permeability. So it could be talking about any of the things that I mentioned just now: poor diet, gut infections, chronic stress, etc. And one of the key principles of functional medicine is that we want to get to the bottom of what is causing symptoms or even manifestations like intestinal permeability, and we want to remove or address those causes or triggers before we try to do anything about the symptom or the manifestation. And the more we can get to the root of the problem, the more effective the intervention will be and the longer term the result will be.

So if we’re just suppressing symptoms or dealing with manifestations of problems, it’s not only going to be less effective, this whatever we’re doing isn’t going to last for as long because we haven’t actually addressed the underlying cause. So with intestinal permeability, if you remove the triggers what’s causing leaky gut the first place—like you fix the diet, you treat the gut infections, the patient starts managing their stress—in many cases you won’t need to even address intestinal permeability because it will take care of itself. One of the amazing things about the cells in the gut is they regenerate every two to three days. And so if you remove the triggers that are causing the problem, then the cells can regenerate and the tight junctions can restore themselves and the intestinal permeability will go away.

So typically in our clinic, we’ll test and treat for SIBO, gut infections, other gut issues, we’ll correct the diet, we’ll address HPA axis dysregulation and screen for heavy metals and mold and other problems like that. And if the patient is still having problems that could be associated with leaky gut, at that point is when we’ll proceed to testing for intestinal permeability.

Testing Options for Intestinal Permeability

So if you look at the research, there are a number of different tests that have been used to define or identify intestinal permeability. And some of these are more common than others, but I’m just going to mention a few different ones and then I’ll tell you what we use in our practice and what I recommend.

So the first is the lactulose/mannitol permeability assay, and this uses molecules, sugars, long-chain sugars called oligosaccharides, and I’ll explain a little bit more about it in a moment.

The second is an antigenic permeability screen, and this looks at antibodies to particular antigens like lipopolysaccharides and then also antibodies to endogenous molecules like actomyosin and occludin and zonulin. So these are proteins that the body produces in the gut that help to regulate tight junction permeability and the structure of the gut and determine whether the gut is permeable or not.

The next marker that’s sometimes used in studies is called D-lactate or D-lactic acid. This is different than lactic acid that you may have heard about that can be high after exercise. This is a product of bacterial metabolism. So it’s produced in the gut. And when D-lactate levels are high, that in some studies has correlated pretty well with intestinal permeability. Butyrate, which is a short-chain fatty acid, has been investigated as a potential marker for intestinal permeability. When butyrate is low, that would be a sign of leaky gut. And then zonulin, as I just mentioned, is a protein that regulates the tight junctions in the gut. That’s being investigated as a marker for intestinal permeability.

But in terms of clinical practice and what’s readily available and what’s been most validated by the scientific research, the lactulose/mannitol test and the antigenic permeability screen, I think, are the two most useful tests.

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The Lactulose/Mannitol Test

With the lactulose/mannitol test, I’m not going to go into a lot of detail because it gets pretty geeky, but it essentially involves measuring levels of two sugars in the urine after the patient consumes those sugars orally. And these sugars have different molecular weights, and then you can look at the results and look at the ratio of those two sugars in the urine and that ratio can tell you whether the gut is permeable and allowing the larger sugar molecules that shouldn’t pass through the gut into the bloodstream or whether it’s doing its job and keeping those molecules out. And so that lactulose/mannitol test is available through labs like Genova Diagnostics, which is a pretty popular functional lab that offers this kind of testing. But there are some definite shortcomings of lactulose/mannitol testing. One of them is that the transport of lactulose or mannitol through the gut barrier is not actually or not necessarily an indicator of malfunction of the intestinal tight junctions. So in other words, a positive result doesn’t necessarily mean that there is intestinal permeability present.

There are a lot of factors that can influence the uptake of those sugars, like GI motility, use of medication like NSAIDs, the surface area of the intestine, gastric emptying, mucosal blood flow, etc., and so these variations can affect the result. But they don’t necessarily mean that the gut is permeable. The other thing is that some studies have shown that only really large molecules, larger than 5,000 daltons, can change the permeability of intestinal epithelial cells and then result in an inflammatory response in the body, which is really what we’re concerned with. And lactulose and mannitol are below 500 daltons, which means they’re much smaller than that, and that suggests that they may not be appropriate as challenge molecules for an intestinal permeability test. So that may have been a little more geeky than I intended it to be, but the takeaway is that the lactulose/mannitol test can give us some information about permeability. But it does have some limitations and it probably shouldn’t be used exclusively. It should maybe just be part of an overall workup that also uses the antigenic permeability test.

There are some ways to increase lactulose/mannitol testing accuracy. One of those is to avoid anything containing lactulose. One of the test molecules that’s used in the diet—and lactulose is not really in a lot of foods, but it’s found in heat-processed dairy and nondairy beverages like soy milk, for example, or some yogurts. You want to avoid mannitol for 24 hours prior to the test, and that’s found in brown seaweed, celery, carrot, coconut, cauliflower, cabbage, pineapple, lettuce, watermelon, pumpkin, squash, cassava, pea, asparagus, coffee, olives and berries, and chewing gum. So you’ll probably have to refer to the transcript for a list of those. You want to generally avoid dairy products for 24 hours before the test, and on the day of the test you want to just avoid drinking too much water, period. And those things can help increase the accuracy of the test. But as I said, it’s still potentially, there are some other issues with it that are more difficult to overcome. I think it’s useful, but it shouldn’t be used in isolation.

The Antigenic Permeability Screen

So the second test for leaky gut is called the antigenic permeability screen, and this was developed by Doctor Aristo Vojdani in Cyrex Labs. In large part, they developed the test because of the shortcomings of the lactulose/mannitol test that we just talked about. Since the lactulose and mannitol are small molecules that don’t necessarily initiate an immune response, Doctor Vojdani wanted to create a test that would better reflect pathological permeability of the gut, which again is really what we’re concerned with. So instead of using larger sugars, he decided to screen for antibodies to proteins and bacterial endotoxins, since those are the major concern when it comes to immunoreactivity. And we know that uptake of these kinds of antigens, proteins and bacterial endotoxins, plays a significant role in the pathogenesis of gastrointestinal and autoimmune disease. In other words, there are a lot of studies showing that inappropriate transfer of these proteins and endotoxins from the gut into the bloodstream initiates an inflammatory response that can contribute to autoimmune disease. And this explains the connection between leaky gut and autoimmune disease. Less than 10 percent of subjects with a genetic susceptibility to autoimmune disease actually progressed to having clinical autoimmune disease in their lifetime, and this suggests that environmental triggers like toxic chemicals and infections and dietary proteins are probably involved in the development of autoimmune disease.

So I’m not going to go into a lot of detail about exactly how this test works because it’s pretty complex, but it’s a blood test. The lactulose/mannitol test that we were talking about earlier is a urine test. This test is only offered by one lab that I know of right now, which is Cyrex Labs. It’s called Cyrex Array 2, and you can check it out at CyrexLabs.com. It needs to be ordered by a clinician. So unfortunately you can’t just order this on your own as a patient, and it is a blood test. And so they draw a blood sample and then they test for antibodies to lipopolysaccharide, they test IgM, IgG and IgA antibodies, which if positive is an indicator of gut permeability and dysbiosis, because lipopolysaccharide is produced by gram-negative bacteria. Those tend to be more pathogenic types of bacteria. Then they test for IgA antibodies to actomyosin, and if those are positive, that indicates epithelial cell damage and that would be an indicator of gut permeability. And then they screen for IgG, IgM, and IgA antibodies to occludin and zonulin. And those are proteins that regulate tight junction. And so if you get a positive result there, that’s an indicator that the tight junctions have been damaged.

And so there are different types of intestinal permeability, and that’s what these different markers give us information about. So those are the two main types of testing that I use in the clinic for intestinal permeability. I’ll say that I don’t actually find myself testing for intestinal permeability very often for the reasons that I mentioned. Typically we tend to look at the underlying cause of intestinal permeability and address that. And if we do a good job with that, in most cases, the intestinal permeability will resolve on its own. When we do test for permeability, we use these two different tests, and I also pay attention to D-lactate. D-lactate can be obtained by running a urine organic acids panel from a lab like Great Plains Labs or also Genova Diagnostics. And if D-lactate is very high then, and especially if Cyrex Array 2 or the lactulose/mannitol permeability tests are positive, I would think it very likely that intestinal permeability is present. So you kind of put together these various tests and along with looking at the history of symptoms and the more indicators you have pointing towards gut permeability, the more likely it is that it’s present. And that’s really the best that we can do from a testing perspective at this point.

Okay, so thanks again, Kent, for your question. Thanks everybody for listening, and I will talk to you soon. We did take a little bit of time off this summer and may have some time off coming up as well. So thanks for being patient in between episodes and hopefully we’ll be back with another episode soon. Thanks for listening.

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Join the conversation

  1. I live in Queensland Australia, am 70, overweight, diabetic, chronic hypertension, chronic pain due to spinal stenosis fibromyalgia and sciatica, all restricting mobility and compounding probable leaky gut and/or IBS.
    It has been going on for so long that I just want to give up!
    Reading this article, I realise that not being able to enjoy eating many foods due to the awful after effects of cramping, diarrhea is identifiable, and I am not alone!
    I don”t digest many foods and dieticians don”t seem to comprehend my list of such foods.
    I try to follow a healthy diet as recommended, but dont know which is worse, feeling sick all the time on a weight reducing diet of salads etc, or eating what agrees with me like plain food (rice, crackers, pasta) that is causing weight gain and all the other associated health issues.
    Grateful for any advice, thanks.

    • Funny, I was saying the exact same thing to my husband last night. Went to see Dr. Pimental at Cedars Sinai in Los Angeles for SIBO and was finally diagnosed with a severe case. The diet he lays out is almost exactly what you have found. Foods like salads make things worse for Sibo, but rice, pasta, bread, etc. are better, making things easier to digest. So, same problem, how to lose weight when I can’t eat the lowest calorie foods, and will do better on the higher calorie? His response was that healing my gut will make it easier for me to lose weight in the long run… Don’t know if that helps but thought I’d let you know you’re not the only one.

      • Thank you so much for replying.
        Although I’m sorry that you are experiencing this, you have no idea how relieved I am to hear that I’m not alone.
        I’m still struggling to find information about any of my symptoms as they don’t fit within the conventional perimeters of general medical practice, and have not yet found someone able to help.
        Therefore, any information you may care to share with me would be enirmously appreciated!
        I will have to look up SIBO. Again many thanks and all the best

        • Go to facebook and look for SIBO. There is a lot of information there. You could also search for Dr. Pimentel from Cedars Sinai. He has a lot of information out there. He’s the main researcher for Sibo. Dr Chris Kresser has interviewed him before and it was very interesting.

    • MO,
      I too suffer from diagnosed fibromyalgia, spinal stenosis from 20ft fall fracturing my head, etc. High BP, gout, stomach cramping so bad my back burns, piriformis syndrome and more. I lost 32lbs on mixed vegetable homemade soups and salads but became totally constipated. I have been taking Zantac for years to eat, and recently read about leaky gut. I stopped the Zantac and started on Betaine HCL with pepsin and Pancreatin (enzymes) before every meal and I have been regular after second day! I forgot to mention I have celiac desease. For my pain and fibro control I roll daily on a white foam roller. Do not buy one with knobs or a stiff roller with an insert. They flare my fibro. So I roll out my buttocks, back, and legs to be able to sleep. Critical to sleeping I bought a new bed. A Therapedic plush that realeases pressure points and allows a descent nights sleep. I get a weekly massage also that is medically necessary to relieve spasm, myositis and stressful pain. If your insurance covers PT or chiropractor, many have a message therapist on board now. If you have an annual health savings account a letter from your MD stating you need message therapy weekly for one calendar year( today it would be prescribed for 3 months through December)for fibromyalgia and you can pay for it that way. My message is 90 minutes for release. Please turn on your favorite music every morning and sing for natural endorphin release rather to watch CNBC and all the negativity in our press. I am down to exercising on my elliptical as it is almost non weight bearing and I did swim but I am sensitive to chlorine. I started getting distilled water to drink and my chronic dry eyes and mouth went away. No more Restasis!! I hope this helps you in some way. Prayer and deep breathing are great releases too!
      God bless you MO!!!

      • Thank you very much for your reply to my post. Ijust read it and will need a bit more time to digest all the information. I will certainly look into it in more detail.
        The first impression I got though is that you too must be suffering a great deal.
        The unfortunate situation we find ourselves in is that all those symptoms are not easily diagnosed and not considered acute enough and therefore not given the appropriate attention by most general health practitioners.
        Your information is therefore very much appreciated. Bless you too

  2. Once a person heals leaky gut, are they more prone to it returning? If so, what should they generally do to maintain a healthy gut and ward off backslides?

  3. problem with cyrex test is that if a patient has depressed gut immunity then you can very well see false negatives since antibodies are not being made to the antigens in the test

  4. Beeturia might be a super easy test. I used to have dramatic beeturia & also anemia (the two are associated, according to studies). After many years on a paleo-type diet, I am no longer anemic, and surprisingly, my beeturia is also completely gone! I believe my gut is less permeable now, due to greater vitamin intake & a healed gut, thus eliminating both problems. I mention it because no where in the literature do I read that people’s beeturia status can change! If I had a friend worried about leaky gut, I would tell them to test by eating some fresh garden beets. Super easy & inexpensive, it’s worth a shot!

    • I have BeetUria – if i eat enough of it… and many of my clients who test negative for gut permeability on the tests above (including cyrex lps) have it too.

      Not reliable.

  5. I know this might not be related to the post but seeing as there isn’t anywhere I could ask. This just an idea with a career choice, I was wondering what could I do to arrive where you (Chris) have today? Would I major in Biochemistry, Nutrition Science? Any help is appreciated, thank you.

  6. Any help appreciated. I have diagnosis of fibromyalgia, gout, twenty years of active leukocytic vasculitis, chronic dry eye and mouth, fasciculations, spasm, on CPAP and hardly sleep due to chronic pain from a 20 ft fall 40 years ago with fractured skull and disc issues c5-6, L5, L2-3 and facet stenosis. I have suffered for twenty years of gut problems and gastritis, and most recently horribly constipated after using the JJ VIRGIN diet. I am gluten intolerant, shellfish anaphylaxis, allergic to tap water(chlorine and trihalomethane)and tested sensitive to a wide variety of foods from close monitoring over nine months with the diet. I am 59 years old. I just started taking Betaine HCL and Pancreatin 3caps and 1cap before meals and my stomach no longer cramps and my back has stopped burning. Continue these products or do you recommend testing for leaky gut? Do you have a recommendation for a functional medicine physician in Arkansas? Thanks for any help. I also have bilateral piriformis syndrome, plantar fasciitis, high blood pressure controlled by meds.

  7. I have a lot of muscle pain or bones not sure what is really hurts. I know is not artritis or rheumatoid or myastenia gravis,, next i want to be tested for celiac dusease and keaking guts….

  8. Very useful information with perfect timing for me. Having been referred to a rheumatologist after elevated ANA levels found, I am now being tested for various IGs plus others. Dependant on my next consultation/results, I now feel empowered to ask more searching questions. I’ve felt for a while now, and certainly after 2 very traumatic bereavements, that things are not right but could not get anything from blood tests my GP frequently ordered until I came down with the worst virus and diarrhoea episode ultimately leading to this referral. I have been on an almost exclusively organic fruit/veg/free range or organic meat and wild salmon diet including bone broths for 3/4 years but it seems I need to get more controlled in my approach to foods. I will be looking at 14four and possibly the GAPS protocol. I am hoping to find a functional doctor here but also learned so much from Chris’s seminar in London last October I should be able to take forward much without needing to stay under the umbrella over the NHS for too long. If anyone knows of a great practitioner in the Midlands or South, please let me know. Thanks for such a wonderful, not too ‘geeky’ talk Chris.

    • Ruth,

      We are based in the UK and run all the functional tests Chris describes.
      I don’t currently have space to take on any more clients – but may do in October – but i have excellent functional practitioners who can help through curoseven.com (which is being re-launched later this month).

  9. Where can a person go to get these tests done? It seems the general practitioners scoff at these things.

    • You can order tests for yourself at DirectLabs.com. You don’t need a doctor’s order, but you need to have a Quest lab in the area to draw the blood (if the test you order requires a blood draw) because that’s who DirectLabs is contracted with.

      The intestinal permeability test is a Genova test that you can order from DirectLabs. It’s a urine test, so no blood draw.

      The zonulin test is from Doctor’s Data, and while DD offers many of their tests thru DirectLabs, I haven’t seen the zonulin test there yet, but it’s new and it might just take time for DirectLabs to offer it.

    • In the UK – we offer the Cyrex Intestinal Permeability Screen – and the Lactulose/Mannitol test as well as Doctors Data and Genova Comprehensive Digestive Stool Analysis and Parasitology.
      curoseven.com (to be re-launched in Late Sept with all updated testing facilities)

    • depends what the gut infection is and what a stool test shows the ‘bug’ is sensitive to be treated with. Dosage needs to be high enough and consistent enough. For some Oregano is too caustic to the gut lining.
      Many Variables.

  10. I took the Genova Intestinal Permeability test and tested solidly in the green for mannitol (which is good/normal), but tested high-yellow for lactulose (borderline/normal). If it’s in the red, that means you have leaky gut.

    In the commentary, it says that I have “normal intestinal permeability.”

    I’m wondering, though, if being in the yellow is really okay, and how quickly that could turn into a leaky gut situation. Anyone have experience with what “yellow” means in this test? Are there degrees of permeability?

  11. Does SIBO need to be treated, or can it resolve itself?

    Paleo diet alone did not “fix” it for me.
    Antibiotics (Rifaximin etc.) did not remove it for me.

    Can it resolve itself after improving low stomach acid production and stress management?

    • Rifaxamin does help the SIBO when my symptoms get unmanageable. I wonder if the leaky gut could be the cause of it?

  12. thanks, I would also be very interested in secretory IgA, particularly very elevated levels measured in stool? what this means and ways to unpack it further

  13. I test high for sibo with a breath test, but test negative twice on several of the leaky gut tests that you mentioned. Why do people keep telling me that I must have leaky gut if I have sibo?

    • RE IgA :

      Immunological activity in the gastrointestinal tract can be assessed using secretory immunoglobulin A (sIgA). Secretory IgA is the predominant antibody or immune protein the body manufactures and releases in external secretions such as saliva, tears, and milk. It is also transported through the epithelial cells that line the intestines out into the lumen. Secretory IgA represents the first line of defense of the GI mucosa and is central to the normal function of the GI tract as an immune barrier. As the principal immunoglobulin isotype present in mucosal secretions, sIgA plays an important role in controlling intestinal milieu which
      is constantly presented with potentially harmful antigens such as pathogenic bacteria, parasites, yeast, viruses, abnormal cell antigens, and allergenic proteins .
      Secretory IgA antibodies exert their function by binding to antigenic epitopes on the invading microorganism limiting their mobility and adhesion to the epithelium of the mucus membrane. This prevents the antigens from reaching systemic circulation allowing
      them to be excreted directly in the feces.

      (So NOT diagnostic of leaky gut – but has contributing role)

      – Curoseven – offer Cyrex and Comp. Digestive Stool Analysis in UK/Europe.

    • SIBO and Leaky Gut CAN be related.
      If SIBO is causing inflammation and there are inflammatory triggers in the diet then increased permeability can occur.

      One does not have to mean the other though.
      Related but not cause and consequence directly.