Probiotics & SIBO with Dr. Jason Hawrelak: Rational Wellness Podcast 329

Dr. Jason Hawrelak discusses Probiotics and SIBO with Dr. Ben Weitz.

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Podcast Highlights

4:30  When Dr. Hawrelak was studying for his PhD, which was focused around dysbiosis and irritable bowel syndrome, he did a literature review on IBS and probiotics and he found studies dated back to the 1950s showing that probiotics were successful in treating IBS.  When we discovered that SIBO is the main cause of IBS in the early 2000s and we have 50 years of research showing that probiotics successfully treat IBS, then why wouldn’t we use probiotics to treat SIBO?  Some would say that it is counterintuitive to take probiotics if SIBO is a condition where you have too many bacteria in the small intestine. But it’s not just that you have too many bacteria, but that you have too many problematic bacteria. It’s too many E. coli or Klebsiella or streptococci, which means that it is more about dysbiosis than it is just about overgrowth of bacteria.  We also need to understand that when we consume probiotics they don’t colonize, so they don’t stay there long term.  This is why when we talk about the 4R program and we come to the reinoculate phase, this just doesn’t happen.  You can’t just take lactobacilli probiotics and increase the amount of lactobacilli in the gut.  On the other hand, while these probiotics pass through, they may secrete some bacteriocins or other antimicrobial compounds that reduce levels of pathogens. They might just secrete short-chain fatty acids or lactic acid, which changes the environment, which reduces levels of pathogenic bacteria.  These probiotics may also secrete short-chain fatty acids or lactic acid, which changes the environment, which reduces levels of pathogenic bacteria.  Some probiotic strains can stimulate the migrating motor complex and help with motility, which is the underlying issue with SIBO. Some can certainly help heal up and regenerate small intestinal cells, and help the healing process after the treatment of SIBO. Some strains or probiotics can reduce visceral hypersensitivity, which is one of the core conditions underlying IBS, where the nerves are hypersensitive to the sensation of gas, or the sensation of feces moving through the colon.  Some can decrease inflammation and some can enhance secretory IgA production.  We just have to use the specific strain of probiotic for the specific benefit we are looking for. 

9:27  Probiotics can be antimicrobial.  For decades we have had case studies of kids with severe SIBO who were hospitalized and antibiotics were not working and they gave them probiotics and the kids got better and got out of the hospital.  Unfortunately, there have been meta-analyses of probiotics that have just lumped studies of various strains of probiotics together, which is like lumping all drugs for hypertension and concluding that drugs successfully treat hypertension.  We need to be specific with strains if you want them to be effective.  There are definitely a handful of studies published each year that show that probiotics effectively treat SIBO.  Lactobacillus reuteri DSM 17938, which produces an antimicrobial substance called reuterin, and is sold around the world as BioGaia, has been shown to reduce the risk of SIBO in kids treated for GERD who were given proton pump inhibitors. 

17:31  When Dr. Hawrelak treats patients with SIBO he will generally choose selectively acting antimicrobial herbals and a prebiotic like partially hydrolyzed guar gum. PHGG is better tolerated by SIBO patients than other prebiotic fibers like inulin, FOS or GOS from a gas production perspective. And then for methane, he might use the BioGaia and Lactobacillus reuteri as well.  Dr. Hawrelak finds using the PHGG to stimulate buyrate production works better than taking supplements of butyrate.

24:22  When Dr. Hawrelak orders SIBO breath testing he does not order the Trio Smart that tests hydrogen, methane, and hydrogen sulfide gases but he continues to do the 2 gas test, but often has patients repeat the test 3 times with lactulose, glucose, and fructose and each for 3 hours.  He doesn’t yet trust the 3 gas SIBO breath test.


Dr. Jason Hawrelak is a researcher, lecturer, naturopath, and nutritionist with over 20 years of clinical experience with a focus on the treatment of gastrointestinal conditions.  Dr Hawrelak is the Head of Research at ProbioticAdvisor.com, which is an incredible database of information about probiotics. Dr. Hawrelak completed his PhD examining the capacity of probiotics, prebiotics, and herbal medicines to modify the gastrointestinal tract microbiota. He teaches and lectures on probiotics and the microbiome all over the world.  He has written many papers and over 20 textbook chapters.  Probiotic Advisor can be found here: https://www.probioticadvisor.com/.  Dr. Hawrelak continues to work with patients at Gould’s Natural Medicine clinic in Hobart, Australia. 

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure.  Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111. Dr. Weitz is also available for video or phone consultations.



Podcast Transcript

Dr. Weitz:                            Hey. This is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field, to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website drweitz.com. Thanks for joining me, and let’s jump into the podcast.

                                                Hello, Rational Wellness podcasters. Our topic for today is probiotics and SIBO with Dr. Jason Hawrelak. SIBO, small intestinal bacterial overgrowth, is believed to be the most common cause of irritable bowel syndrome, or IBS. And SIBO is a condition of too many bacteria in the small intestine.  Now, why would you want to treat it by ingesting more bacteria when you already have too many? But some studies do show that taking probiotics are helpful for both IBS and SIBO. And while some studies show that specific strains such as Bifidobacterium infantis strain 35624 helps with IBS, other studies and meta-analyses just lump various probiotics and often of unspecified strains or mixtures together.   This has created somewhat of a mishmash of research confusion. I’ve talked to Dr. Mark Pimentel about probiotics for SIBO.  And he basically dismissed it, partially because how can you talk about a group of substances?  It would be like saying antibiotics are good for a certain condition.  So saying probiotics are good for SIBO from a scientific perspective, really doesn’t seem to make much sense.   Now, there’s one prominent doctor in the SIBO world who recommends taking triple probiotic therapy, taking a Lacto/Bifido blend of unspecified strains, a Saccharomyces boulardii product, and a spore based probiotic for patients with SIBO. And he says that specific strains don’t matter, just take one from each category.  Some Functional Medicine practitioners have concluded that the best type of probiotic for patients with SIBO, is to take a spore based probiotic, since it won’t open up until it gets into the colon, and therefore will not add to the bacteria in the small intestine. On the other hand, many functional medicine practitioners in the SIBO space do not recommend taking probiotics while treating SIBO, until after you’ve reduced the number of bacteria with appropriate antibiotics or herbal antimicrobials.  And of course, this would make sense based on the Four R or Five R strategy pioneered by the father of Functional Medicine, Dr. Jeffrey Bland, who taught us to remove, then replace, then reinoculate, and finally repair the gut. And so there you would only use probiotics in phase three, the reinoculate phase.

                                                So who better to help us understand this confusion about probiotics for patients with IBS or SIBO than Dr. Jason Hawrelak, joining us from Australia? Dr. Jason Hawrelak is a researcher, lecturer, naturopath, and nutritionist with over 20 years of clinical experience with the focus on the treatment of gastrointestinal conditions. He’s the head of research@probioticadvisor.com, which is an incredible database of information about probiotics. And he also offers a series of courses, that are available adjacent to that program as well.  Dr. Hawrelak completed his PhD examining the capacity of probiotics, prebiotics, and herbal medicines to modify the GI tract. He teaches and lectures on probiotics and the microbiome all over the world. He’s written many papers and over 20 textbook chapters. Dr. Jason Hawrelak, thank you so much for joining us.

Dr. Hawrelak:                     Hey. You’re very welcome, Ben.

Dr. Weitz:                           Thank you.

Dr. Hawrelak:                     I’m glad to be here chatting with you again, about a very interesting and apparently controversial topic, that we’re delving into. Yeah.

Dr. Weitz:                           So why don’t we start by talking about SIBO and IBS? So let’s focus in on SIBO, which a lot of the data seems to show is the most common cause of IBS, probably accounting for 60, maybe as much as 70 or more percent depending upon how we’re able to determine if you have SIBO.  And the way we generally determine if you have SIBO, is with a SIBO breath test. And I’d like you to comment about the SIBO breath test? And especially about the various substrates that are available, that are used in the test including lactulose, glucose, fructose?

Dr. Hawrelak:                     Gosh, I don’t know where to start even.

Dr. Weitz:                            So-

Dr. Hawrelak:                     Maybe I’ll take a step back and go.

Dr. Weitz:                            Yeah.

Dr. Hawrelak:                     Listen, my PhD was specifically around dysbiosis irritable bowel syndrome.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     We were running clinical studies in IBS, giving them prebiotics, and probiotics, and herbs to try to influence their microbiome. This was back, I started my PhD and my honors degree, which followed my PhD in the year 2000. So before people were talking about SIBO as being anything but this really rare condition.  And so I had a chance to do this lovely literature review into irritable bowel syndrome and probiotics. And look back, and found the first studies going back to 1950s, showing probiotics were successful in treating IBS. And not every single strain is, obviously. But the bulk of data suggests that probiotics are helpful for treatment of IBS. That was clear in the early 2000s, when this idea of SIBO came out of… So for me, and then SIBO came out as the cause of IBS. And I’m like, “Well, is SIBO is the cause of IBS, and we’ve got 50 years of research showing that probiotics successfully treat IBS, then why on earth wouldn’t we be using probiotics to treat this, when we already have 50 years of data showing that apparently it successfully treats this condition?”  So that’s what my background was from where people were like, “Oh, don’t use probiotics.” But it’s like if you’re saying this is the cause of IBS, and we’ve got all this data showing probiotics work on IBS, it just doesn’t make sense that we say we should not take probiotics.

Dr. Weitz:                           But it’s counterintuitive, if the problem is too many bacteria, why are you going to put more bacteria in?

Dr. Hawrelak:                     I think it’s counterintuitive if that’s the big viewpoint. Rather than, “Okay, it’s actually not just too many bacteria, it’s too many problematic bacteria.”

Dr. Weitz:                           Right.

Dr. Hawrelak:                     Or it’s too many streptococci, or too many E. coli, or Klebsiella that are there. And when you understand that differently, that changes things. Because it’s like, “Okay.” Because I think that conception around SIBO is changing. And in fact, there’s more of a thinking now that it’s more about dysbiosis than it is about just overgrowth of bacteria. And you could have overgrowth of some bacteria and never have an issue with it. And you have overgrowth of Klebsiella, or E. coli, or Streptococci and you get symptoms associated with it. And potentially gut damage too in the small bowel.  So I think with that understanding, it’s like, “Okay. Well, what do we know that probiotics can do?” I think there’s this misconception, and this goes back probably to the Four R or Five R type stuff with reinoculation. You can’t reinoculate with probiotics. This is an old myth that we should really make sure we toss out. And certainly I teach within the functional medicine program at the University of Western States, and we change that reinoculate to restore.  It’s like, get with the new century, we can’t reinoculate with Lactobacilli, and Bifidobacteria, and products, it’s not reality. We can help restore populations that are too low, but it gets into that idea of colonization. So I think the idea that, “Oh, we’ve got more bacteria. We just add more and then they just permanently live there,” that’s not reality.  That’s not what happens when we take Lactobacilli, or Bifidobacteria, or Saccharomyces, or et cetera. They do not permanently live in your small bowel or large bowel. They’re temporary visitors, so they’re passing through. But while they pass through, they may well secrete some bacteriosins or other antimicrobial compounds that reduce levels of pathogens. They might just secrete short-chain fatty acids or lactic acid, which changes the environment, which reduces levels of pathogenic bacteria.  Some probiotic strains can stimulate the migrating motor complex and help with motility, which is the underlying issue with SIBO. Some can certainly help heal up and regenerate small intestinal cells, and help the healing process after the treatment of SIBO. Some strains can reduce visceral hypersensitivity, which is one of the core conditions underlying IBS, where the nerves are hypersensitive to the sensation of gas, or the sensation of feces moving through the colon.  Some can decrease inflammation, some can enhance secretory IgA production. So if we start looking at the possibility of what probiotics can offer here, it makes total sense that we can use them as tools to actually help. So there’s different ways of reducing or changing bacterial ecosystems. Antibiotics is one way, sure. But probiotics is another way, and herb medicines are other ways of actually changing ecosystem composition. And I think-

Dr. Weitz:                           So would it be accurate to say in some cases that probiotics are antimicrobial?

Dr. Hawrelak:                     Yeah. Well, it would be from a SIBO perspective. And I think again, maybe 20 years ago, it would’ve been there was a lack of research around probiotics in SIBO specifically. Yes, the use of probiotics in IBS, the dataset was all clear around that. There were successful case studies of kids with severe SIBO who were hospitalized, and antibiotics weren’t working where they gave them probiotics, and the kids got better and got out of hospital.  So there were successful case studies of treatment with probiotics of severe life-threatening SIBO in the 1990s that were published too. So there was already some preliminary data that suggested that probiotics would be helpful. But skip forward now, and look at the data out there’s study after study showing probiotics are helpful for a treatment of SIBO. And I think you can’t just have your head in the sand and say, “This doesn’t exist.”   And while I agree with Dr. Pimentel that there are issues with meta-analyses, where you just grab all probiotics and shove them together. It’s like saying, “Let’s do a meta-analysis of do drugs treat hypertension?” Well, some do, some don’t. But if you shoved the ones that don’t in there with the ones that do, you’re going to actually get an unclear effect. You’re not going to see anything.  And that’s definitely a problem with probiotic meta-analysis, where researchers who are unaware of this fact will just grab all probiotics and shove it together. And listen, some won’t work. If your probiotic strain you’re giving doesn’t have selected antimicrobial properties, or won’t help with motility, then is it going to work with SIBO? Yeah, perhaps not. Whereas ones that actually do have antimicrobial properties do seem to work for SIBO.  And I think, again, you look at, there was a meta-analysis in 2017, I think it was, where they took all the probiotic studies for SIBO. And I think they found that… Again which had some issues with methodology because I think it’s grouping all the things together. Which if anything, it precludes beneficial effects, makes it harder to see. But even doing that, there is a 53% eradication rate, clearance of SIBO with probiotics in the studies when they pulled the data together.  And since that was published, there’s more and more studies published each year looking at it. Not like 50 studies a year, but there’s a handful of studies published each year supportive of the use of probiotics to effectively treat SIBO, and bring down breath gas with EPI hydrogen, or methane, or both.

Dr. Weitz:                           Now, is the best way to think about this, some people have described it sort of as a parking lot and here’s only so many parking spaces, and if you park the good bacteria in there, there’s no parking spaces left for the bad bacteria? Almost like if we’re having some elaborate game of musical chairs, and the bad bacteria don’t end up with chairs if there’s enough good bacteria there?

Dr. Hawrelak:                     That’s definitely a component there. And I think the other additional bit is whether that microbe can produce something that is antimicrobial?

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     And I think a good example here is Lactobacillus reuteri DSM 17938, which is sold around the world as BioGaia. There’s a clinical trial giving it to kids with reflux disease, who were given proton pump inhibitors to treat the reflux. And we know that PPIs, that is very consistent around this increased risk of SIBO development.  So this study was like, “Okay, what if we give them this probiotic? Will it prevent these kids from getting SIBO?” And they tested, baseline tested, three months later. SIBO developed in, I think, it was 56% of people in the placebo group, 6% of those in the BioGaia group. That’s a massive difference from a prevention perspective.

Dr. Weitz:                            Yeah. For sure. Absolutely.

Dr. Hawrelak:                     But what’s unique about this strain, is this strain produces an antimicrobial substance called reuterin. And it may be that is the key reason why it works in that situation. And the dose they’re giving is like a hundred million CFU twice daily, I think was the dose. So relatively small.  Yet there was another study, a similar population of kids taking proton pump inhibitors for their reflux, and they gave a combination of Lactobacilli and Bifidobacteria at much higher doses. It did not work, did not prevent SIBO. And it’s like, “Okay, well do those specific strains have any indication they would be helpful in this condition, as in producing antimicrobial substances, et cetera?” No, they don’t have that.  So to me it was like, “Oh, okay. Well yeah, if we choose our products wisely, we can get therapeutic benefit.” And if we just use random products with no sort of good rationale for the use, I think we’re going to hit-and-miss more often than we actually hit. Whereas I think when we are actually using stuff that has theoretical rationale for their use, we’re going to get better results.  And if we as researchers actually chooses the ones that have theoretical evidence of use through research, we’re going to get better outcomes than just grabbing, “Hey, here’s a random probiotic, let’s see if it works for SIBO prevention.” Versus, let’s choose one that has the traits and qualities we’re after.

Dr. Weitz:                           Is it possible?

Dr. Hawrelak:                     We do this in probiotic researchers all the time, they’re looking for how do we choose the best probiotic for treating vaginal bacterial vaginosis? It’s like, let’s see the ones that survive, have the good pH tolerance, produce D-lactic acid, inhibit the growth of those pathogens. And you might get a hundred strains to start with. And you put them through a bit of an obstacle course, and you come up with three or four that actually tick all the right boxes. And then you take them into studies from that point onwards.  And I think this also illustrates, I think some of the differences you said initially around do strains matter?  Yes, strains do matter. We can clearly see that in that kind of research, where you can have 20 strains of Lactose crispatus for example, and only some will have all the criteria that you need to be like a successful general probiotic.  And just like we have numerous strains of Lactobacillus reuteri, only some produce reuterin. So if you’re supplementing with this strain of Lactobacillus reuteri that does not produce reuterin, you cannot expect it to have the same effect as the ones that do produce reuterin, like the BioGaia one that was used in that successful SIBO case. And that same strain have been used in methane cases too, where it actually significantly reduced methane output. And it cleared methane in a number of people in that study as well.

Dr. Weitz:                            Oh, interesting. Because that was going to be my next question, which is how specific can we get? Can we take the results of a SIBO breath test, find out the patient has hydrogen SIBO, and we know certain organisms tend to cause that? Or is it hydrogen sulfide, or is it methane? And then are there specific strains that you would recommend for each type of SIBO?

Dr. Hawrelak:                     Yeah. And I think as more research comes to the fore, and we have access to some of those strains, we’ll get better data around this area. And again, I was recently looking at the probiotic SIBO literature, and there’s a number of studies that have been published out of China, where they’re a bit vague in their description of the probiotics that they use in these studies.   So it’s hard to necessarily as a clinician take that into clinical practice going, “Okay. Well, this combination of probiotics worked in this Chinese study. Can I use these strains?” Well, they don’t detail the strain they tell you the species. So as each year goes on and we get more research, we will become better at fine-tuning and matching these things up. But currently we know that the reuteri DSM 17938 is helpful for methane. That is clear.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     And then-

Dr. Weitz:                           Now, is it possible to simply recommend that for a patient with methane SIBO without anything else?

Dr. Hawrelak:                     Yeah.

Dr. Weitz:                           Is that something you’ve done?

Dr. Hawrelak:                     Only in kids.

Dr. Weitz:                           How would you treat-

Dr. Hawrelak:                     Only in kids. Yeah.

Dr. Weitz:                           Only in kids? Okay.

Dr. Hawrelak:                     Because they can’t necessarily take the foul tasting herbs that I would usually use in adults. Yeah. So certainly they can work brilliantly well on their own in some people.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     But generally I do my best to get the best result as quickly as possible with patients, in a way that doesn’t harm their colonic microbiome in any significant sense. So I’m trying to choose selectively acting antimicrobial herbals, a prebiotic like partially hydrolyzed guar gum. And then for methane, I would use the BioGaia, Lactobacillus reuteri as well.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     Yeah. But for some kids who can’t do the herbs. Well, I might just use BioGaia and partially hydrolyzed guar gum. And yes, you can see results in some of those people with just that simple treatment.

Dr. Weitz:                            And partially hydrolyzed guar gum you would pick, because unlike a lot of prebiotics or forms of fiber that tend to feed SIBO bacteria, that has been shown not to exacerbate SIBO symptoms, right?

Dr. Hawrelak:                     Yeah, it’s an interesting fiber, I think. We just did a systematic review of this just recently, actually. But I think there’s nine studies using it for irritable bowel syndrome, and all of them were positive. So that’s what got me excited when I read these studies on IBS, this goes back to 2016 when I first came across it, 2015 or ’14.  Not that long ago, but unaware of it before then, do a literature search. I’m like, “Oh, my God. Look at this substance I was completely ignorant of.” And it’s got all these studies showing it not only reduces bloating and distension, and normalizes bowel pattern in patients with IBS. And it works for constipation from IBS or diarrhea from IBS. So we’ve got that data.  And then there are studies using it for showing that it decreases methane output in people that have high methane. And then we have studies where they gave it alongside Rifaximin to treat SIBO. And I think from memory, the eradication rate with partially hydrolyzed guar gum was 85, 86% versus 60% with just Rifaximin on its own. So it significantly improved the outcome. And this was hydrogen dominant SIBO.  So for me, PHGG is integral whether I’m treating hydrogen dominant SIBO or methane. And it is tolerated by most people with SIBO, not all, there’ll still be some that react to it. But compared to other prebiotic fibers like inulin, FOSS, or galacto-oligosaccharides, it is definitely better tolerated from a gas production perspective.

Dr. Weitz:                            And do you tend to use that a couple of times a day? And do you tend to use it away from meals, or with meals? Or it doesn’t matter?

Dr. Hawrelak:                     With the PHGG, it can be with or without meals it doesn’t matter. And generally it’s once a day to ease compliance with that one.

Dr. Weitz:                            Oh, okay.

Dr. Hawrelak:                     So it’s six or seven grams, one hit. And it’s easy to work with because you can mix into, unlike some fibers, it mixes beautifully into cold water. And it’s got almost no flavor. So you can mix into a cold drink and it makes the water a bit thicker, but not really much flavor. Easy to mix into smoothies, or easy to add to breakfast cereals, porridge, whatever you might actually have. It’s easy to work with.

Dr. Weitz:                            Do you know, or can you speculate what is it about PHGG, partially hydrolyzed guar gum, why it has this different quality from many other forms of fiber or prebiotic?

Dr. Hawrelak:                     Yeah. It’s definitely for most people less gas forming. And I think that’s part of it. And I think we know it also feeds butyrate producing species more so. So if you look at what species utilize substances that we eat, if we have inulin-FOS, then we feed Bifidobacteria, and Faecalibacterium, Akkermansia, for example are three populations that tend to increase. Whereas with partially hydrolyzed guar gum, we need a little bit of Bifidobacteria, but it’s often it’s Roseburia and other-

Dr. Weitz:                           Akkermansia?

Dr. Hawrelak:                     Not so much Akkermansia, interestingly enough. But it’s more of a butyrate producing species.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     So it’s kind of feeding a different group of bacteria, that generally perhaps are not overgrowing in the small bowel. We don’t tend to see butyrate producing species don’t really show up on any of the literature looking at what’s overgrowing in the small bowel in patients with SIBO. It’s usually Streptococci or Proteobacteria that show up in the vast majority of studies to date. So they can’t utilize it as a food source so much then.  But how exactly to improve the efficacy of Rifaximin in SIBO treatment is an interesting thought. And the researchers initially were doing it because it is a prebiotic like substance, and they were using it that way. We know it does improve efficacy, but the mechanism, I think, is a little bit less clear.  Whereas when it comes to methane, I think it’s more clear in that we know that methane producing bacteria, typically Methanobrevibacter smithii is the key one for most people, likes living in a more neutral to alkaline pH. And doesn’t like being bathed in butyrate. So if we ingest a substance that creates more butyrate, we create the conditions that are less conducive to the growth of methane producing bacteria.

Dr. Weitz:                            What about just adding butyrate as a supplement in such cases of methane SIBO?

Dr. Hawrelak:                     Yes. You can certainly use that as an adjunct agent too. What you can have though when you use just butyrate, is you can have a… Essentially taking a step back, what does the methane producing bacteria consume?  Methanobrevibacter eats hydrogen gas.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     If you change the circumstance where you just reduce the levels of methane producing bacteria, the hydrogen gas level can actually increase.  So sometimes you can actually have worst bloating or distention from giving butyrate, even though it’s actually dealing with the underlying methane overproduction. But you end up with more hydrogen in the shorter term, which can mean more symptoms as well.  So I think I have played a bit with that.  And I think it can be useful tool in sometimes, but you just have to be-

Dr. Weitz:                            So essentially what you’re telling us is anytime you have a patient who has methane SIBO, there may be hydrogen SIBO that’s being masked by the fact that the increased number of methanogens are consuming the hydrogen?

Dr. Hawrelak:                     Yeah. And this is clearly the case if it’s methane in the small bowel, for sure. Because we’re supposed to have hydrogen produced in the colon, so that’s normal. So if you see a lack of hydrogen rise in the colon, but you see a spike in the rise in methane or breath tests, that clearly shows that’s the case.  But in the small bowel, again, if you see that rise in methane at the 20 or 40 minute mark on a breath test, you know there’s hydrogen producers there. Because that’s what’s eating the substance first, they’re eating the lactulose, or the glucose, or the fructose first. They produce hydrogen gas, that’s eaten by the methane producing bacteria very quickly, and you get the spike in methane, not necessarily of hydrogen.  So yes, you would actually have hydrogen producers underneath there, that you have to deal with too. And that’s what butyrate itself does not do. So I think it’s arguably better for chronic methane issues than small bowel methane issues.

Dr. Weitz:                            So in terms of small bowel, large bowel, when we do the SIBO breath test there’s a time cutoff and there’s some controversy about that. Is it 90 minutes? At one point it was a hundred minutes. Is it 120? I’ve talked to some prominent SIBO practitioners who always believe in doing a three-hour test, because they don’t trust that it might only be two hours-

Dr. Hawrelak:                     Yeah.

Dr. Weitz:                            … and they want to see what happens.

Dr. Hawrelak:                     Now, I always do three hour breath tests.

Dr. Weitz:                            Oh, you do?

Dr. Hawrelak:                     Always, for extra hydrogen and methane.

Dr. Weitz:                            Okay.

Dr. Hawrelak:                     But I always do lactulose and fructose at a minimum. And often lactulose, fructose, and glucose.

Dr. Weitz:                            Oh, really?

Dr. Hawrelak:                     Yeah. Yeah.

Dr. Weitz:                            Are you checking for hydrogen sulfide as well? Is the trio-smart available in Australia?

Dr. Hawrelak:                     It is. I can arrange it for my North American patients. But I tend not to use trio-smart so much. I tend to stick with the QuinTron based testing for hydrogen and methane for the most part.

Dr. Weitz:                            Why?

Dr. Hawrelak:                     Why? I think I’ve seen some results, apparent discrepancies of even some people, the same person a minute apart, sending the breath samples to different labs, or even three. A couple went to the more classic ones that do hydrogen/methane, and one went to the lab that does trio-smart. And the level of hydrogen and methane was the same in the two normal labs. But completely, completely, totally different in the trio-smart one. A hundredfold, a lot different.  And I’ve just seen that enough, that I’m just a little bit hesitant to know what to do with that, when the levels of methane and hydrogen are multitudes lower on that test consistently than I see on the other tests. I’m a little bit like [inaudible 00:26:17]-

Dr. Weitz:                            Interesting. You think that has to do with the way the gases are collected? Or do you know why?

Dr. Hawrelak:                     Good question. No, I don’t. It is just been enough that I’ve just been hesitant to go, “Okay.” I’m just not fully personally going to trust those results. I’m going to stick with the more conventional labs, because the way that this shows up with the hydrogen and methane seems consistent between them.

Dr. Weitz:                            Interesting.

Dr. Hawrelak:                     And I’m comfortable with that. Yeah.

Dr. Weitz:                            And you might be missing out on hydrogen sulfide though?

Dr. Hawrelak:                     Well, I am basing that on because I’m testing lactulose, often glucose, and fructose. And if they-

Dr. Weitz:                            Okay. All three of those?

Dr. Hawrelak:                     All three.

Dr. Weitz:                            That’s a lot of testing. You’re talking about, especially if you’re asking everybody do a three-hour test, that’s nine hours of testing?

Dr. Hawrelak:                     It is. It is. But it’s so much more accurate, the information you get. And this is maybe two years ago now, I went through and said, “Okay, let’s take the last 130 people we’ve suspected of SIBO, and done breath testing for. If we just only did lactulose, only lactulose, how many people would we have picked up with SIBO?” And it was 73% of those people with SIBO we picked up with just lactulose. If we did fructose alone, only fructose, 85% of people. If we did-

Dr. Weitz:                            Really? Fructose is more accurate than lactulose?

Dr. Hawrelak:                     I reckon it is. And listen, we need further clear… I don’t have my own hospital setting where I can do aspirate and culture on people to verify things. So what I’m using is essentially that same criteria, rise of 20 parts per million at 90 minutes, whether that be with glucose or fructose.  Because for me, why are we defining SIBO by if it eats glucose, it’s SIBO, but if it eats fructose, it’s not SIBO at the 20-minute mark? That’s just stupid to me. It’s like there are bacteria there eating sugar that aren’t supposed to be there.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     Whether they’re eating glucose or fructose, it’s still bloody SIBO. I don’t understand where people are like, “Oh, no. It’s only SIBO if it’s a glucose or lactulose.” But if the same bugs are eating lactose, it’s no longer SIBO. It’s like, “Of course it’s SIBO, because it’s defined by the time where the gases are produced. Not by the sugars that are consumed.”

Dr. Weitz:                            Well, actually when it comes to methane, time doesn’t even matter anymore. Right?

Dr. Hawrelak:                     No. That’s right.

Dr. Weitz:                            Because now it’s IMO and it could be in large intestine?

Dr. Hawrelak:                     That’s right. Yeah.

Dr. Weitz:                            So are you routinely doing stool testing as well?

Dr. Hawrelak:                     Yes. Yeah.

Dr. Weitz:                            To see if there’s methanogens? Okay. You are?

Dr. Hawrelak:                     Yeah. So we’re looking for methanogens, which don’t always show up on stool tests, I must say.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     Breath testing is far better accuracy for picking up methane status, for sure. But also looking for hydrogen sulfide gas producers on stool tests too. So let’s say if I’m suspecting SIBO, and there might be hydrogens sulfide as the background as a possibility, we do lactulose, we do fructose, we do glucose. The glucose and fructose completely normal. No sign of excess. No bump at all, because there shouldn’t be any bumps with hydrogen. And methane’s normal. Lactulose flat lines to three hours.  At this point I’m thinking, “Okay, this is possibly hydrogen sulfide SIBO, what does the microbiome picture look like? Do I have elevated levels of hydrogen sulfide gas producers on that? Or do I have-“

Dr. Weitz:                            So those are the Desulfovibrio, and what-

Dr. Hawrelak:                     Yeah. And Bilophila, they’re the two classic ones.

Dr. Weitz:                            Okay. Yep.

Dr. Hawrelak:                     You can also have those Fusobacterium that would rarely be involved, but can be.

Dr. Weitz:                            Okay.

Dr. Hawrelak:                     And Proteobacteria. Some Proteobacteria would overproduce hydrogen sulfide too. So you’d be looking at those. But the classic ones would be Bilophila and the Desulfovibrio. And not all stool tests sadly tests for Bilophila, it’s harder to find. And I think I wouldn’t use a stool test that doesn’t tell me about Bilophila, to be honest. Because it’s such a commonly overgrown hydrogen sulfide gas producer, that if you don’t test for it you would never see it, and you won’t know how prominent it is.

Dr. Weitz:                            So which stool tests include Bilophila?

Dr. Hawrelak:                     The ones that do shotgun sequencing, like shotgun metagenomic sequencing. So that would be things like NirvanaBiome, CosmosID in the States, and Microba here in Australia. And Microba sends kits overseas too. They will test for Bilophila and the Desulfovibrio off the top of my head.

Dr. Weitz:                            I know Desulfovibrio is on the GI-MAP. I’m not sure about-

Dr. Hawrelak:                     That one is a bit easier to come by, for whatever reason people have gone, “Oh, let’s focus on Desulfovibrio.” Yeah, Bilophila is actually in my experience looking at thousands of stool samples, is more often overgrown than the Desulfovibrio. Because Bilophila, its name gives it away, Bilophila, it loves eating bile, bile’s its thing. So you tend to see a bloom in people who do keto type diets, or high fat diets, high saturated fat diets tend to have these major blooms of Bilophila.

Dr. Weitz:                            Oh, interesting.

Dr. Hawrelak:                     And it’s just sad that you can’t see it. Because if you’re doing a stool test that can’t see Bilophila, you have no idea that this diet is feeding, blooming these hydrogen sulfide gas producers in [inaudible 00:31:02]-

Dr. Weitz:                            And there you are doing a low-carb diet thinking you’re starving your bacteria, and you’re actually feeding some of them?

Dr. Hawrelak:                     Feeding some of them? Yeah, that’s right. So to me, I would not do any stool test that does not do Bilophila. Because you need to be able to look at that. Yes, so I would look at that. I’d also look for acetogens too. There are certain bacteria that we know that eat hydrogen and convert it through to acetate. So you’re not going to get any breath gases with that. So you have to get them in a stool test too.

Dr. Weitz:                            Oh, wait a minute, which ones are those?

Dr. Hawrelak:                     They’re less characterized at this time point.

Dr. Weitz:                            This is new breaking news.

Dr. Hawrelak:                     Well, interesting. It’s been around for a long time, but it just hasn’t been discussed even that much for some reason. Listen, even the methane constipation stuff. I moved house recently, and I had to sort through my papers in my garage. I had boxes and boxes of papers that I collected as part of my PhD, and I was painstakingly giving them away.

Dr. Weitz:                            You know they’re all on the internet now?

Dr. Hawrelak:                     I know, that’s why I gave them away, most of them. But I came across one paper from the 1980s, and they were looking at methane output in people who were constipated. And they’re like, “Hey, I think there might be a correlation here between people who are constipated and a high methane output.”   And not only that, they gave them tons of sulfur as a supplement. And these people shifted their hydrogen dynamics from methane to hydrogen sulfide from the sulfur. And their bowels sped up, and they no longer had constipation. And this is research in the 1980s.

Dr. Weitz:                            Wow. Ugh.

Dr. Hawrelak:                     And we forget that stuff like that, people were on it at that point, but some people were.

Dr. Weitz:                            Wow.

Dr. Hawrelak:                     Because they were already looking at where does the hydrogen go? It could be methane or hydrogen sulfide, and let’s see if we can shift it between that? And they could, and effectively treat constipation by giving sulfur. So whether that’s an approach we want to be doing? I don’t know, because hydrogen sulfide gas is not particularly great. So I don’t think we want to be shifting people from tons of methane to tons of hydrogen sulfide. But it was interesting they were doing it.

                                                But one of the other pathways that hydrogen can go to, is it can become acetate. So we have a number of groups of bacteria in our colon, hydrogenotrophs who eat hydrogen. So methane producing archaea, hydrogen sulfide gas producing bacteria. And then we have the acetogens, those that eat hydrogen in make acetate. And that’s not a gas, and that’s a lovely short-chain fatty acid with anti-inflammatory effects.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     So that’s obviously, which would be great if we could have more of that going on. In fact, I’m on a bit of a tangent here, but I just read a study in Japan recently. And they were looking at methane producing status, and acetogens in this Japanese population. And I think it was only seven percent of the Japanese population had methanogens present. Whereas for Westerners, it’s like 90% of us have got methanogens in our gut.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     And Japanese, their rate of constipation is very tiny. And a lot of their hydrogen goes become acetate in Japan. Whereas for Westerners, that’s more of a rare situation. So you could-

Dr. Weitz:                            What is some of the species that are acetogens?

Dr. Hawrelak:                     One of the key ones we see is Blautia hydrogenotrophica, I think from memory. Yeah, [inaudible 00:34:05]-

Dr. Weitz:                            Wow. Never heard of that one.

Dr. Hawrelak:                     … hydrogenotrophica. No. Again, you need to be using the right stool test to see that one, and that’s where you would have to use shotgun metagenomic sequencing that you can get down to the species level, to look to go what sort of Blautia do you have, and whether you’ve got the acetate, the ones that essentially consume hydrogen to make acetate as a consequence.  And the cool thing is too, that particular species can actually cross feed Faecalibacterium. So you now have this beautiful relationship where we have this guy that eats hydrogen and it makes acetate, and it shares some of the acetate with Faecalibacterium prausnitzii who makes butyrate with that shared acetate. So to me it’s a beautiful relationship, and this is why we should be trying to encourage acetogenesis when we possibly can.  But essentially that occurs when the pH in the colon is much lower. So when we have a pH of five and a half or less, we tend to have much more capacity for acetogens to thrive, whereas they don’t live in a neutral pH that we tend to see in Westerners. So you can also be looking at stool pH as one of the markers that can help indicate whether that flat line is hydrogen sulfate or it’s [inaudible 00:35:18]-

Dr. Weitz:                            Because we’re all drinking our alkaline water to make ourselves healthier?

Dr. Hawrelak:                     But I think it’s a lack of fiber for the most part.

Dr. Weitz:                            Oh, okay.

Dr. Hawrelak:                     Because if you don’t eat plant foods, you don’t eat fiber, you don’t produce short-chain fatty acids, you don’t get the change in pH in water.

Dr. Weitz:                            So essentially you’re saying that Americans are full of shit?

Dr. Hawrelak:                     Well, Australians and Canadians too, I’m going to say. And they often are. There’s often days worth of poo inside of those populations. A lot of patients I work with have got days worth of poo that are there. I remember one patient I got them to do the… And this is one test I do for all patients. But I get them to do the bile transit time test, it’s a very low tech test. You eat some corn on the cob or some black quinoa, you don’t chew it, write down exactly when you eat it, you write down when it starts coming out, and when it finishes coming out in your poo. But my champion one is, I think it was 25 days before the corn started coming out.

Dr. Weitz:                            What?

Dr. Hawrelak:                     Yeah. And she was only pooing every two or three days. So I knew it was going to be slow, but I had no idea be that slow.

Dr. Weitz:                            Oh, my gosh. 25 days? Wow.

Dr. Hawrelak:                     Yeah. And you just think how much fecal matter is loaded in that colon constantly?

Dr. Weitz:                            Yeah. Wow.

Dr. Hawrelak:                     And no wonder she was chronically unwell, and felt horrific all the time. It’s like, “Yeah. Well, that explains a lot of it there.”

Dr. Weitz:                            And how did you treat that?

Dr. Hawrelak:                     This is a patient maybe 10 years ago. So we’re going back fair while, I can’t recall, but we certainly focused on trying to speed up transit time. And-

Dr. Weitz:                            Did you ever get her colonic?

Dr. Hawrelak:                     Listen, I think a colonic would’ve been helpful in the short term. I’m a bit cautious around the potential impact on the colon from a long-term perspective.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     But I think as a let’s get week’s worth of poo? Sure, to get you feeling a bit better. But I much prefer working from this way than that way. Although I don’t think the odd enema, I think, is not going to be an issue. But I do think colonics where you’re washing the colon a bit more, you’re likely to have more changes to the microbiome as a consequence.

Dr. Weitz:                            Do you think that some of the new generation of probiotics like Akkermansia is now available, and I think that fecal bacteria, [inaudible 00:37:26] is starting, I think it’s available?

Dr. Hawrelak:                     Probably not far of, I would reckon. Yeah.

Dr. Weitz:                            Not far off. So these are anaerobic strains that hadn’t been available because of the difficulty of producing them?

Dr. Hawrelak:                     Yes.

Dr. Weitz:                            And I’ve read some that they may potentially be colonizers of the gut in some cases. What have you seen?

Dr. Hawrelak:                     Yeah. I can only speak clinically thus far with my patients who’ve taken the Pendulum Akkermansia and Pendulum Glucose Control.

Dr. Weitz:                            Right. Right. Yep.

Dr. Hawrelak:                     And I have not seen Akkermansia show up on any stool test yet. When my patients have taken it.

Dr. Weitz:                            Okay. Okay.

Dr. Hawrelak:                     When they did have Akkermansia beforehand. I had high hopes. I was excited. I’m like, “Maybe we can, because we’ve tried to revive your Akkermansia population, it is extinct in your gut, you did not have it. Maybe we can recolonize with this supplement.” But thus far, and listen, it’s only been maybe 10 to 15 patients. So I’m not-

Dr. Weitz:                            Okay.

Dr. Hawrelak:                     … saying no, it never does it. But I have not seen it do it in any of my patients thus far. And they’ve been taking the supplement at the same time they’re doing the stool test even. And it hasn’t even showed up on the stool test, which I was slightly sad about. Because I thought at least if it showed up when they took it, it’s a bit positive around that. And maybe a chance of it sticking around.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     But it haven’t showed up when they’re taking it so far.

Dr. Weitz:                            Interesting.

Dr. Hawrelak:                     Yeah. And it’s first generation Akkermansia, so who knows? Maybe wasn’t selected as the core attribute was how good it could colonize. Because I think there’s some discussion around in general our current generation of Lactobacilli and Bifidobacteria do not colonize in any significant degree in kids or adults. Yet, if we gave the same ones to moms when they’re pregnant, they can actually colonize that infant for life. So it’s interesting. There’s a window where-

Dr. Weitz:                            Oh, really?

Dr. Hawrelak:                     … they could permanently colonize. Yeah, interesting enough.

Dr. Weitz:                            Interesting.

Dr. Hawrelak:                     But it won’t in all the populations. But there’s one study with one type of Bifidobacteria, its code strain was maybe AH2106 or something. I could be a little bit off with that one. It’s been a few years since I read the study. But it did colonize in 30% of people, I think from memory, for up to six months.

                                                So it’s like, “Okay, if a strain is chosen where the main criteria is it can stay, and maybe they’ll screen hundreds of different types of Bifidobacteria to find one with that long-lasting capacity to colonize.” So I would say that in the future we might have Bifidobacteria that can colonize, we might have Akkermansia, or Faecalibacterium that can colonize. I would just say perhaps at the moment, we certainly don’t have that in general with Bifidobacteria. And at least in my experience, we don’t have that with Akkermansia yet.

Dr. Weitz:                            Do we know specific prebiotics that can make certain bacteria flourish in the gut, especially maybe ones that are really low?

Dr. Hawrelak:                     Yeah. For sure. And I think this is where prebiotics shine, is where you’re trying to make specific changes to that ecosystem going, “Okay, well you are…” And this is something that I do in my practice all the time, I do analysis. Okay, “You’re low in Bifidobacteria, you’re low in Akkermansia,” let’s say hopefully they’re there.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     They’re maybe just a thousandfold less than where you’re happy to be, or a hundredfold less than what they should be.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     Then yes, you could go, “Okay, well let’s go inulin-FOS,” or otherwise known as oligofructose-enriched inulin. Very good at feeding both Bifidobacteria, and Akkermansia, as well as Faecalibacterium. So you have this substance that we can generally effectively used to target increased population of those three species, without feeding other things for the most part in most people.  And then partially hydrolyzed guar gum, good for a range of butyrate producing species. Then we have galacto-oligosaccharides, which would be Bifidobacteria and Faecalibacterium for the most part. But GOS can also decrease hydrogen sulfide producers like the Desulfovibrio and Bilophila. And inulin-FOS can also decrease Bilophila populations too.

Dr. Weitz:                            Oh.

Dr. Hawrelak:                     So we can use these tools to decrease levels of bugs we don’t want, and at the same time encourage levels we do want. And that’s the thing I absolutely love about prebiotics, is that capacity to, let’s say your gut’s overgrown with Proteobacteria, you’ve got large amounts of Proteobacteria? A prebiotic like lactulose, which I think kind of gets a bit of a bad name in the US because it’s the food source in the lactose breath test. But it reduces the levels of Proteobacteria brilliantly well in the colon. It is amazingly effective at doing so.

                                                You’ve got studies showing that. And I can say from 20 years of practice having using lactulose, it effectively reduces Proteobacteria populations in the gut. So you can use something that is increasing levels of good guys, decreasing levels of pathogens, all at the same time. [inaudible 00:42:24]-

Dr. Weitz:                            So you’re saying for hydrogen sulfide, SIBO, FOS, and GOS combination might be part of an effective strategy?

Dr. Hawrelak:                     Yeah. You’d have to gauge what their tolerance, because sometimes they will get… One thing that hydrogen sulfide gas does is induces visceral hypersensitivity. So it makes the nerves in the colon more susceptible to gas related pain and discomfort. So you have to gauge where your patient’s at with that. Because if they’ve had H2S overgrowth for a long time, often visceral hypersensitivity can be intense.

                                                So you do anything that increases gas production in the colon such as give GOS or inulin-FOS, that gas discomfort will cause excruciating discomfort and pain. So you have to approach it differently, depending on where they’re at with their symptoms, and how far along they’ve had this H2S issue with. Because if you get them early on, and they don’t have that damage yet? Then yes. Because essentially what we should be getting when we adjust GOS or and inulin-FOS, is farting.

                                                We should just get flatulence. If our gut’s working beautifully, just gas, that’s it. But if we have issues there where we have bloated, distension, pain, cramping, worsening constipation, there’s something else underlying that we need to deal with. And those tools may not be appropriate at this time point. And we might use other strategies.  I think luckily with hydrogen sulfide gas producers, for the most part Bilophila, it eats bile. So you’re just like, “Okay, make sure they’re not taking ox bile supplements.” That can cause a massive bloom in hydrogen sulfide gas producers, that most people again aren’t aware of if you didn’t test for Bilophila. But reduce saturated fat, that’s a very quick and easy way to deal with Bilophila for most people.

Dr. Weitz:                            Well, but bile helps break down any kind of fats. Why saturated fat?

Dr. Hawrelak:                     Well, it’s a sulfur compound. When we’re ingesting dairy fat in particular, but also other saturated fats, the sulfur content in our bile is higher for whatever reason.

Dr. Weitz:                            Oh.

Dr. Hawrelak:                     And that feeds Bilophila to a far greater degree than if you eat olive oil.

Dr. Weitz:                            So you want to reduce the bile and the sulfur?

Dr. Hawrelak:                     Yeah. Yes, both. But particularly it’s about changing the types of fat consumed. But sometimes it’s overall fat too. But certainly you don’t tend to see Bilophila blooms from olive oil, avocados, nuts, and seeds. Even if they’re gorging on them, that does not happen. It is from dairy fat, butter, ghee, coconut oil, palm oil, those are the things that will cause blooms of Bilophila.  So it’s often easy to deal with that by changing diet. Now, they can also be encouraged by supplements like chondroitin sulfate or glucosamine sulfate. Again, that aren’t always on people’s radar. And sulfur based preservatives, synthetic ones used in processed foods. So we’ll cut out those.

Dr. Weitz:                            Oh, you’re saying those, they contain sulfur so they could feed-

Dr. Hawrelak:                     And they can feed hydrogen sulfide gas producers too. Yeah.

Dr. Weitz:                            Interesting.

Dr. Hawrelak:                     So when people take chondroitin sulfate or glucosamine sulfate long term, which is often the case for things like osteoarthritis, we have to be aware that they can negatively impact the colonic ecosystem by encouraging the growth of hydrogen sulfide gas producers over time.

Dr. Weitz:                            Yeah. There’s studies showing that glucosamine sulfate reduces cardiovascular events by 30%. So it’s real beneficial for cardiovascular as well.

Dr. Hawrelak:                     Yeah, it’s an interesting substance in that way. And I think it’s just worthwhile keeping tabs on how that individual person’s ecosystem is responding to that dose of sulfur, and whether they’re having a bloom of hydrogen sulfide gas producers or not as a consequence of its use?

Dr. Weitz:                            Interesting.

Dr. Hawrelak:                     Mm-hmm.

Dr. Weitz:                            What do you think about biofilm busting? Is that something that should be done in combating SIBO? Do bacteria that cause SIBO encase themselves in a biofilm? And does that make it… For example, the methane producers tend to grow in the mucus and that’s sort of a biofilm. So does that mean you need to… You know what? I talked to Dr. Rahbar one time, and he was saying that he thinks that taking Akkermansia, which eats mucus, that that makes it easier to get at the methane SIBO.

Dr. Hawrelak:                     Oh, that’s an interesting idea. And certainly Akkermansia is one of the species in the gut that does indeed consume mucus, Faecalibacterium does as well, and others. But an interesting idea, yes.

Dr. Weitz:                            Right. Now, coming back to what about using agents that supposedly break up biofilms to make it easier to get rid of the gas producing bacteria?

Dr. Hawrelak:                     Okay. My main concern here is that beneficial bacteria live in biofilm too. Because I think this is conception that some people have-

Dr. Weitz:                            Okay. Got it.

Dr. Hawrelak:                     … that bad guys live in biofilm and the good guys are just playing around and don’t. And it’s like, “That’s not true.” They do too. So if we’re giving something that is non-selective, and breaks down biofilm of all bacteria good and bad, then we’re actually harming beneficial species too.  Unless you’ve got an agent that can selectively and only break down the biofilm of pathogens and leave the good guys alone. And you could research that before you marketed your product. You could do that research in vitro and go, “Hey. Look, our biofilm busting product doesn’t break down Bifidobacteria, or Faecalibacterium, or Akkermansia biofilm. But it does Klebsiella and E. coli,” wouldn’t that be great? But they don’t do that. Generally it’s like, “It kills bad guys, so therefore it must be fine for everyone to take [inaudible 00:47:49]-“

Dr. Weitz:                            Is there any biofilm busting agent that you know of where they have done that, looked at that?

Dr. Hawrelak:                     Not in that kind of sense. But we do know that herbal medicines, well, look at pomegranate husk. So the skin of the pomegranate fruit markedly antibacterial against pathogenic bacteria, leaves Bifidobacteria alone. And would actually leaves lactose alone, and encourages the growth of Bifidobacteria. So you have a selectively acting substance, that can break down the biofilm pathogens. We’ve got clear data around that, both bacterial and fungal pathogens. But actually encourages levels of beneficial species. So for me it’s like, “I’m going to use that, thank you very much. As my tool to try to target overgrowth.”

Dr. Weitz:                            Where do you get get pomegranate husk from, though?

Dr. Hawrelak:                     Well, interestingly enough, listen, it’s used in traditional Chinese medicine for 1,800 years.

Dr. Weitz:                            Okay.

Dr. Hawrelak:                     It’s been used in Ayurvedic medicine for over 2,000 years. It was used by Western herbalists and European herbalists up until probably about a hundred years ago, widely. It just dropped out in North American and Australian practice in the last maybe 50 years or something like that. You can find old herbalists in the early 1900s talked about using it too.

Dr. Weitz:                            Huh.

Dr. Hawrelak:                     I don’t know why it dropped out. But you could do a PubMed search of pomegranate husk. Punica granatum is the botanical name, antimicrobial, or even Google Scholar it, and you’ll get hundreds of papers. It’s so well researched as an antimicrobial agent.

Dr. Weitz:                            Yeah. But it doesn’t-

Dr. Hawrelak:                     It kills worms, it kills Giardia, it kills Entamoeba, kills a range of fungi, it kills pathogenic bacteria but leaves good bacteria alone. And for me, I’m just gobsmacked that there aren’t more people in industry who are like, “Oh, my God. Look at this, something that’s got hundreds of research papers on it. Why don’t we make a product with that?”  And listen, it is happened here in Australia. I’ve been talking about the wonders of pomegranate husk for 20 years. And now there’s like four or five different products with pomegranate husk on the market for clinicians to access. But in America [inaudible 00:49:45]-

Dr. Weitz:                            Oh, okay.

Dr. Hawrelak:                     … to go there. You can buy the powder, you can buy organic pomegranate husk powder.

Dr. Weitz:                            Oh, really?

Dr. Hawrelak:                     What I love too is it’s a waste product. It’s like they’re throwing it out anyway, so it’s no ecological concerns about its use. We’re not like finding some rare herb, or something.

Dr. Weitz:                           Where do you get organic pomegranate husk powder?

Dr. Hawrelak:                     Well, there’s a brand in the states it’s called eSutras, E-S-U-T-R-A-S, that does organic pomegranate husk, pomegranate skin powder, pomegranate peel. And as more people are aware of it, more people will start requesting it. And then that’ll make a change in terms of how accessible it is.

Dr. Weitz:                           Interesting.

Dr. Hawrelak:                     But as I said, unlike some things where we worry about ecological concerns about harvesting Goldenseal, or Coptis, or something like that-

Dr. Weitz:                            Right.

Dr. Hawrelak:                     … because they’re these rare slow growing plants. This is the waste product of a huge industry, that we can get bioorganic pomegranates, we can get organic skins, and we can make medicine from that. And we should be given its research base, it’s long use over thousands of years, and its selectivity of action.

Dr. Weitz:                            Yeah. I know you’ve talked on other podcasts about being worried about some of the antimicrobials as potentially damaging the microbiome as well?

Dr. Hawrelak:                     Yeah. And that came directly out of my PhD research, where we were looking at the impact of herbs on the microbiome. And I was like, “Oh, look at the herbs that cause harm.” And it just occurred to me, what are these herbs doing to our good guys? And no one had done any research around that back in the early 2000s.  So I was like, “Okay, I want to do this in vitro experiment of trying to grow these beneficial bacteria, expose them to a range of different antimicrobial herbs and see the impact.” And it was fascinating to see, because there were some substances like the berberine containing herbs like Goldenseal or Coptis chinensis that were amazingly good at killing Bifidobacteria. They’re good at killing Bifidobacteria, Lactobacilli were more resilient. But there wasn’t a dose that you could kill bad guys without harming beneficial species.

                                                But there are other things like garlic, that could kill Candida and a range of pathogenic bacteria, and completely leave good guys intact. Whereas if you got the dose of garlic up high enough? Yeah, it would harm the good guys as well. So for me, that was a pretty pivotal research project, that really changed my thinking around this stuff. Going, “Okay, well these verbs can cause harm. Maybe we should choose the ones that are acting selectively.” And that’s really been the core of my practice since early 2000s, when I did that research project.

                                                And now we have clear data on some studies looking at long-term berberine use in blood sugar control. And yeah, it does. And it brought down blood lipids and improved blood sugar control. But it hammered Bifidobacteria populations, it decreased butyrate producing species, it decreased diversity of the ecosystem. And perhaps most surprisingly caused blooms of E. coli, Klebsiella, Citrobacter, and a range of Proteobacteria bloomed with long-term use of berberine.  Which I think was fascinating, because I was not expecting that. I was expecting Bifidobacteria diversity can go down with its long-term use. And probably butyrate producers with long-term use. The short-term use doesn’t seem to have such a big impact. But I was not expecting blooms of harmful Proteobacteria associated with long term berberine use.

Dr. Weitz:                            I heard you say something like that. I did a little data searching on berberine. And there were some papers that even showed that it was beneficial for butyrate producers, that it has a beneficial effect?

Dr. Hawrelak:                     Yeah. And I think short-term versus long-term is one of the factors.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     And there’s a couple of studies out of China, that they used hundreds of participants. They’re actually large studies and with three months of use, versus two weeks of use, or four weeks of use. And then you saw different patterns. We saw the blooms of Proteobacteria, the clear decrease of Bifidobacteria, and clear decrease of butyrate producers. And we may not see that decrease of butyrate producers in the short term studies.

Dr. Weitz:                            Okay. So when you’re talking about berberine, there are different products on the market. And I was talking to one of the manufacturers. And they said, “Look, when we are trying to use berberine as an antimicrobial, we’re giving you berberine from all these different herbs mixed together. When we’re using berberine as a blood sugar, and actually berberine is one of the few substances that’s been shown to reverse atherosclerotic plaque in arteries, when we’re using it for that purpose, we’re using berberine hydro…” What’s it called?

Dr. Hawrelak:                     Hydrochloride, probably.

Dr. Weitz:                           Hydrochloride, yeah. And that has a different action than berberine being derived from herbs. Do you think that makes a difference?

Dr. Hawrelak:                     No. I think it’s got to do with absorption. I think that’s what’s key is that berberine derived from Coptis, I think, it’s going to be same as berberine hydrochloride from an action standpoint. I think it’s whether it’s absorbed or not? And berberine, the challenge with berberine is it’s very poorly absorbed for the most part. Because our peak glycoprotein pump doesn’t like it.  So it’s gets into the cell, and your enterocyte’s like, “Oh, I don’t want this thing,” and spit it back out into the lumen of the gut. So because of that, most of the berberine you ingest stays in the colon, where it interacts with the ecosystem. And long-term causes harm to that ecosystem.  Now, there are ways of probably trying to enhance the absorption of berberine. And there are some companies that have focused on that, where they can combine it with Phosphocholine, the same way they do with turmeric or Boswellia, they combine.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     Or green tea extract, they can combine it with Phosphocholine which increase absorption. Clinically I’ve used black pepper or piperine to improve the absorption of berberine as well, to get it out of the gut into the bloodstream. For me, I’m using it to treat dental abscess infections, where I want the antimicrobial action of berberine, but I don’t want it in the gut, I want it in the bloodstream. And piperine turns off peak glycoprotein pumps and enterocytes. So you actually end up with a ton more berberine in your bloodstream if you take it with piperine.  So there are ways of modulating it, so you can increase the absorption and decrease colonic damage with its use. But I think it’s imperative we’re aware of the fact that it does harm the microbiome with long-term use too. Because we might have options, like if we go, “All right, berberine is one way of controlling blood sugar. But so is Nigella sativa, black seed.” Tons of studies on that showing very similar results. And you don’t get the microbiome harm with black seed.

                                                So I’m like, there’s often, often choices. With atherosclerosis, I came across a study that used, I think it was Pycnogenol and Gotu kola, showing clearance of artery plaque with long-term use. And again, I’m much more comfortable using that for months to years than I am berberine. I don’t mind using berberine for two weeks, no issue at all for just treating Giardia as something, I don’t mind using it for two weeks. Or I don’t mind again, treating a dental abscess where I’m giving it with, or other systemic infection, with black pepper to enhance the absorption for 10 to 14 days.  But I’m really cautious with any more than 14 days use. And we don’t necessarily know at what point we get that more substantive microbiome harm with berberine. We can just say the studies that looked at three months, definitely showed the damage that was done. So for me, I’d certainly be cautious that it’s something to recommend on a daily basis for years, such as substance.

Dr. Weitz:                            Yeah, I haven’t seen that. But… Yeah. Yeah.

Dr. Hawrelak:                     Yeah, it would be interesting if you did shotgun metagenomic sequencing with all your patients pre and post.

Dr. Weitz:                            Oh, okay. Yeah.

Dr. Hawrelak:                     So you do that beforehand, do it after three months, and see the impact. I can just say that I’ve seen it with my patients.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     And I’ve seen the research is clear with long-term use, there are certain patterns that you start seeing with it that are not positive.

Dr. Weitz:                            You just mentioned turmeric. I’ve been using curcumin, a highly absorbed form of curcumin to help some patients with visceral hypersensitivity.

Dr. Hawrelak:                     Yeah.

Dr. Weitz:                            I’ve seen a couple of papers on that. What do you think about that?

Dr. Hawrelak:                     Yep. Love it. I love it. And I use it heaps for that same purpose too. I use Iberogast lots for that.

Dr. Weitz:                            Okay.

Dr. Hawrelak:                     Iberogast, it’s a herbal combination.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     For whatever reason it’s hard to come by in the US. But in Australia and in Europe it’s much easier to find.

Dr. Weitz:                            Yes. Somehow for a while it wasn’t available at all.

Dr. Hawrelak:                     Yeah.

Dr. Weitz:                            And something happened with the manufacturer, or I don’t know.

Dr. Hawrelak:                     Yeah, I’m not sure. We had constant access to it here, so I’m not sure what happened overseas. But it’s something that effectively decreases visceral hypersensitivity with patients. Because I think I’ve got some patients who have IBS and they go, “Oh, I’ve tried Iberogast for two weeks and it didn’t decrease my symptoms.” I’m like, “Well, yeah.” We’re lucky if it decreases the symptoms, and a lot of people it will decrease bloating, and distention, and abdominal pain, and cramping for sure.  But we’re using it to decrease visceral hypersensitivity. And that takes three plus months of use to see that kind of benefit. And I use it all the time with a well-absorbed turmeric phytosome extract, so that they’re… And usually within three to six months there’s a massive improvement in their visceral hypersensitivity. Which means that their diet can be expanded, they can have more onions, and garlic, and legumes, and other things that nurture a wide range of beneficial microbes they may have had to cut out, because their gut was so sensitive to gas pressure.

Dr. Weitz:                           Interesting. So some people might be able to tolerate a much lower level of gas, if so, it’s not just about getting the gas down?

Dr. Hawrelak:                     Oh, totally.

Dr. Weitz:                           It’s… Yeah.

Dr. Hawrelak:                     Yeah. That’s very clear from the IBS research that, yeah, there is some research showing that people with IBS have produced more gas. But there’s more research showing that they’re sensitive to the gas being produced. And I always tell this example to my patients, but they put these special balloons up their butts and they pump up those balloons, and people with IBS will complain of pain when the balloon is this full, whereas normal people would when the balloon is that full, before they get the same degree of pain and discomforted.

Dr. Weitz:                           Right.

Dr. Hawrelak:                     Because the nerves are just hypersensitive. And that can be pretty extreme in some cases.

Dr. Weitz:                           It depends if you take the population from West Hollywood or not. I’m just kidding. So what do you think about soil-based probiotics?

Dr. Hawrelak:                     Ah. Listen, I’ve been organic gardening for over 30 years. I love it. And I organic garden all the time. I’m with nature, and I’m drinking creek water, and exposing myself to lots of wild microbes. And I think that’s important.

Dr. Weitz:                           Are you drinking creek water?

Dr. Hawrelak:                     I do drink. Well, not from a dirty source obviously. But if I’m out in the rainforest and it looks clean? Yes, I’ll drink creek water. I was out in Canada up in the highland Rocky Mountains where again, I don’t think people were peeing and pooing upstream. And I’m happy drinking creek water. And I wouldn’t even worry if it was like healthy people peeing or pooing to be honest. It’s just like people who don’t have such healthy gut ecosystems or are have Giardia or something, I don’t want to drink their downstream water.  But it is an interesting way of picking up microbes from the environment, anyway. And I think we even know that interestingly though, even having a more diverse garden, if you have a wider diversity of plants growing in your garden, you have a more diverse gut ecosystem as well. So we are certainly always picking up microbes from the environment. Generally it’s temporary, usually.

Dr. Weitz:                           Oh, so I’m really referring to spore-based probiotics?

Dr. Hawrelak:                     Well, you are talking about soil-based ones too. But I suppose I’m just taking the conversation a bit further. Yeah.

Dr. Weitz:                           I think spore-based are often referred to as soil-based?

Dr. Hawrelak:                     Yeah.

Dr. Weitz:                           Right?

Dr. Hawrelak:                     Yeah. And I think that-

Dr. Weitz:                            And are they the same or not?

Dr. Hawrelak:                     Well, I don’t think all soil-based ones will be spore formers, for sure not.

Dr. Weitz:                           Okay. Not. But spore are soil-based? Okay, I see.

Dr. Hawrelak:                     But certainly the ones that people are often marketing, they are spore based. And originally probably derived from soil as well.

Dr. Weitz:                           Okay.

Dr. Hawrelak:                     Yeah. I think there’s a growing body of evidence building around the use, which I’m really happy to see. I think they were over hyped initially compared to the evidence base. And I think that’s changing is more evidence comes onboard. So for me it’s always around evidence, if there’s evidence that this product is safe and efficacious, whether it comes from soil, or it comes from the skin of litchis, or it came from some healthy Swedish person’s gut, or another Swedish person’s breast milk?  Like the reuteri DSM 17938 came from someone’s breast milk, for example. I’m totally happy to use it if it’s safe and efficacious. And again, I don’t mind if it’s coming from soil or whatnot. I just think that the evidence base for them as class compared to Bifidobacteria, or Lactobacilli, or even Saccharomyces is just a lot less at the moment.

Dr. Weitz:                           Right.

Dr. Hawrelak:                     But there’s research on Bacillus coagulans. GBI306086, I think from memory is its code name, strain name, that for rheumatoid arthritis. And there’s no other probiotic with good data for rheumatoid arthritis. So I will definitely use that in that condition for sure. So I think if it has something that’s unique or better evidence based, I would totally use them irrespective of where they came from.

Dr. Weitz:                           Right.

Dr. Hawrelak:                     Yeah. And I think just sometimes the generalizations out there sometimes are a bit much, of like, “Oh, coming from the soil, therefore we should all be ingesting it.” It’s like, “Well, what soil? Where, which part of the world?” Soil would be different elsewhere. The assumption that something that lived in garden soil is going to be a happy in your gut growing at 37 degrees in quite a different environment than soil is a bit much too, if you’re expecting it to permanently colonize.   But we know that sometimes you can pick up bugs from soil, and have them stay for long periods of time. And we know that people who are active gardeners in summer, they can have a tremendous number of increased microbes. Some people, compared to what it’s in winter when they’re not actively gardening, where you have temporary visitors of these soil derived microbes as well.

Dr. Weitz:                            You mentioned a specific probiotic that helps with rheumatoid arthritis. The GI-MAP stool test which we tend to do a lot, has a section where they have bacteria that may be correlated with autoimmune conditions. And there’s a certain amount of data showing that those specific bacteria, that there’s a certain level of correlation with specific autoimmune conditions. And so if those bacteria are overgrown, the idea is maybe if I could reduce that bacteria, maybe we could have some benefit. What do you think? Where are we? Is it still pretty speculative?

Dr. Hawrelak:                     Oh, I think it’s a bit speculative. But we see disease associations [inaudible 01:04:14] certain patterns with certain disease states all the time. And I can say I’m a clinician too. So I’m a researcher clinician, I see patients. So I see what works and what doesn’t work. And I’m happy to prescribe things that work clinically too, that haven’t even been researched necessarily yet either.   So I’m okay with some relatively novel stuff of going, “Okay, there’s a study that shows that low Akkermansia or low Bifidobacteria in eczema seems to be a common pattern.” And I go, “Okay. Well, I will increase Bifidobacteria in my eczema population.” And clinically you see good results by doing that in terms of decreased allergies and decreased reactivity. So I’ll base my decisions along that too.  So I think yes, there’ll be a degree of speculative that’s there, but you might have to again trace that back. I’m not familiar with all the microbes that they associate with increased risk of autoimmunity.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     And you might just want to double check that. And going, “Okay. Well, do I concur by my view of the connection between those ones?”

Dr. Weitz:                            Sure. Yeah.

Dr. Hawrelak:                     But I’m open to that approach in general, of the different disease associations, associate diseases with different microbiotic patterns. And how we can modify that to change the disease process. Because that’s something I do every day in clinical practice, and see the results of.

Dr. Weitz:                            Cool. Great. Awesome discussion. Jason, thank you so much. I could ask you a hundred more questions. But I appreciate your time and I respect it. So tell our listeners and viewers about the things you have to offer, the Probiotic Advisor, your courses, where can they go?

Dr. Hawrelak:                     Yeah. So we set up the Probiotic Advisor as an independent, evidence-based, accessible information around probiotics. So you can take industry out of the way, out of the equation and go, “What does the evidence say about this probiotic strain for this condition?” So it’s a searchable database, where you can type in a condition or a product, and you can work out what the research says it should be used for.   And that’s been going for a number of years. And that’s one of my babies that came out again, of wanting people to be as evidence-based when possible, in choosing… We really wanted to improve outcomes with patients, that’s what it boils down to. And if we can do that by using evidence to go, “Okay, this product chain works for this condition, this one doesn’t?” Use the one that works, don’t use the one that doesn’t.   And don’t even just guess, maybe it’ll work. Just use the one that works. And I also offer a range of courses through the Microbiome Restoration Center as well. And I’m mostly targeting clinicians, because I love teaching clinicians around gut health and microbiome restorations. So we have two general courses, natural and functional medicine approaches to gastrointestinal conditions.

                                                And then another 10 week course, which is Advanced Microbiome Manipulation. Which is all about some of the concepts we talked about today. But about different testing approaches in different labs and interpretations. But also how to modify ecosystems in beneficial ways. In a way that, for me, the thing that came out of my PhD looking at the wonders of the microbiome, I’ve been indoctrinated in the wonders of the microbiome from the late ’90s when I started my first reading around the microbiome, is choosing therapeutic approaches that minimize harm from the microbiome perspective. Which is an old naturopathic concept of first to no harm.

                                                And I think if we have choices of tools, we can choose berberine or we can choose pomegranate husk? I’m going to choose pomegranate husk. If I can get the same outcomes, without the negative outcomes on microbiome perspective, I will choose that first. So that underlying philosophy that runs through my teaching, is to optimize ecosystem and minimize agents that cause harm, or interventions that cause harm as much as we can.  And also being aware. Like I had a patient last week who, a ketogenic curated diet for child epilepsy made a huge difference, huge difference to having daily seizures that were uncontrollable, to having mild seizures daily from doing a ketogenic diet. But our focus will be on how do we maintain your ecosystem health, when you’re on this diet that you need to be on because it’s really helpful for you? How do we make sure you’re still feeding your beneficial bacteria? And how do we prevent the bloom of harmful species, that over the long term could potentially actually be counterproductive to what we’re trying to achieve in terms of neurological inflammation?  So I think always having that, as how do we optimize microbiome health for this person? And how do we choose agents that are most likely to do that, at the forefront of our minds as clinicians.

Dr. Weitz:                            That’s great. And if listeners want to work with you?

Dr. Hawrelak:                     Yeah. I do see patients through Gould’s Natural Medicine, which is my clinic down in Hobart, although I’m not in Hobart now. But I see patients internationally, I’m completely online these days.

Dr. Weitz:                            Right.

Dr. Hawrelak:                     Yeah.



Dr. Weitz:                            Okay. Great. Thank you so much. Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would certainly appreciate it if you could go to Apple Podcasts or Spotify, and give us a five star ratings and review. That way more people will discover the Rational Wellness Podcast.  And I wanted to let everybody know that I do have some openings for new patients. So I can see you for a functional medicine consultation for specific health issues like gut problems, autoimmune diseases, cardiometabolic conditions. Or for an executive health screen to help you promote longevity, and take a deeper dive into some of those factors that can lead to chronic diseases along the way.   And that usually means we’re going to do some more detailed lab work, stool testing, sometimes urine testing. And we’re going to look at a lot more details to get a better picture of your overall health, from a preventative functional medicine perspective. So if you’re interested, please call my Santa Monica Weitz Sports Chiropractic and Nutrition Office at 310-395-31-11. And we can set you up for a new consultation for functional medicine. I’ll talk to everybody next week.


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