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Digestive Disease Week 2023 Research Update by Dr. Ali Rezaie (June 2023)

Hello and welcome. I'm your co host, Siobhan Sarna, founder of CboeSOS. And I'm here with my fellow cohost, doctor Alison SeBecker. Hi, Alison. Hello?
Who? Hello, my friend. Who is the founder of Cibo info and lifelong student and unfortunately an advocate for all of us just like I am. About Cboe small intestine bacterial overgrowth, and she is a Cboe patient herself as MI. And doctor Siefecker and I started collaborating I don't know how many years ago now, Alison, like, 2016.
And as a result, we have been working to educate the world about out these conditions. Cbo, chemo, IVS, and what to do about it. Now, we have a very special guest. His name is Dr. Ali Rezai.
And we use the excuse that DDW Digestive Disease Wait 20 23 has completed and we use those as a prompt and a lover to get him to come on and talk to us. So we would love to talk to him every day, but We make it this annual tradition. And if you haven't heard of doctor Ali Rezaai, you will hear more about him in the world of gastroenterology who certainly is well known. He is a specialist in irritable bowel syndrome gut microbiome internal UV therapy. Fascinating.
He's published well over a hundred research articles in peer reviewed journals, including Gastroenterology, American Journal of Gastroenterology, Digestive Diseases and Science and Canadian Sciences and Canadian Journal of Gastroenterology. Now, his work has been cited more than counted 8000 times by other scientific journals. He serves as the Associate Editor of The Journal of Digest of disease and sciences. He is out of Cedar Sinai and medical director of the gastroenterology, motility Cedar Sinai Medicine. He is director of bioinformatics and biotechnology, medically assisted associated, excuse me, science and technology program, also known as masked program at Cedar Sinai.
He and his colleague, Dr. Mark Pimentel, are changing the world in terms of the microbiome. Mapping the small intestine microbiome and helping us all come up with ways to live, with cboe and emo, small intestinal bacterial overgrowth, and in intestinal methampagin overgrowth. Until they come up with a cure, no pressure, high doctor Rezai.
Hello. And thank you so much for that kind introduction, and it's a pleasure to be here again.
Yeah. We love having you. We love having a fact. Yay. So tell so Digestive Disease Week, the largest gastroenterology conference, just sort of wrapped.
And I know you all were presenting some phenomenal information. Tell us what your highlights what are you excited about? What do you want the world to know about?
Yeah. So I'm I'm very optimistic. The world is moving very fast, especially in the field of microbiome. And we have been playing around with microbiome and trying to modify it. And now we're seeing that the treatments and the diagnostic tests are getting to a point that patients can be helped.
And that's the eventual goal. And that is very exciting to see. And every time that we see new technologies, new developments, and all of those will help, you know, delineate exactly what we need to do and what's bacteria need to be targeted, what fungi need to be targeted, what viruses need to be targeted, and what is the interaction between these 3. Right? So and also the Orkea.
So it's it's exciting times and happy to share some of those data and talk about them. Whichever route you want to take it.
Yeah. Well, it's okay with you. Can we talk about IMO, Methanage, and Overgrowth? Because a lot times I get feedback on our YouTube channel and in the Facebook group. We know now closing in on about 30000 people.
They're like, Okay, I don't hear enough about IMO. I hear a lot about Cboe, which if you could explain the nuance between those 2 conditions, so there's no confusion that they're totally different because that happened for a little bit. Yeah. And then let's start there and we'll we'll move along, though.
Yeah. Absolutely. That just maybe we step back. So all of these fall under microbial overgrowth syndromes. Right?
So these are diseases that certain group of microbes. Overgrow. And obviously, when that balance goes away, they cause trouble. So the most known condition under that category is obviously recebo. But then we have small intestinal fungal overgrowth when the fungi is overgrowing.
And that becomes a problem. And we can talk about that as well because there was a lot of data about that at DDW as well. And then when the methanogens increase. So And remember, eventually, we will figure out what happens when the viral components of microbio will be imbalanced. So So that will come, but obviously the research in that field is much tougher and harder considering the bacteriophages and also viruses.
But what are the RK? RK? If you think about domains of life, so we have life, and then it breaks down into 3 categories. It breaks into Orkia, it breaks down into bacteria, and then breaks down into eukarya. So what do you carry is essentially all the fungi, all of us, everything with, like, big cells.
But then on the other side, or the rkea and bacteria, and they're completely different. They're different domains of life. They're as different as they are to bacteria as we are to bacteria. They're that different. They completely do different things.
And they they were the original microorganisms that showed up, and that's why they can produce different gases such as methane that you're now understanding what's the role of these gases as well. So traditionally, we considered Arkea, which produce methane, to be harmless guys. They're just hanging out and they have don't have much of a role, they're just there. But obviously, that's not true. Whenever you ignore part of nature, you just get burned at the end.
And now we're understanding that most of the times actually they are there to help us, but sometimes they can just behave abnormally and they can cause a a problem. So 1 of the gases that they produce is methane. They do produce other gases as well. And what's interesting is that by itself methane is active in our body. So there's some gases in our body that they don't have much of a physiologic effects, for example, hydrogen.
Hydrogen is just the gas goes around doesn't attach to any receptor. It just causes a little bit of a trouble at this extension, and then eventually we breath it out. The CH4 or methane is different because it does have physiologic effects. And if the best example of gases having physiologic effects, what we call actually gas transmitters are the ether. Right?
And all all the gases that we use in and it's sthesia. So those those are just gases. If you think about it, they just go in, allothenes goes in, and then 20 seconds later, you're unconscious. Right? So these are gases that can have physiological effects.
And methane is 1 of them. And what we have shown is that they can affect the function of smooth muscles. Smooth muscles are the muscles that we don't have roll over. We have 2 types of muscles. Right?
So we have skeletal muscles in our body that we have control over, the way that I'm moving my hands. But we have smooth muscles that are in our heart, that are in our guts, bladder, uterus, and these we do not have control over, and our body controls them. Methane can affect the function of these smooth muscles, and the primary site that it affects is gut So it leads to spastic contractions of the smooth muscle. So the movement of the gut is not as good and that leaves obviously to abdominal cramps. And when the bowel is not moving, when it comes, dispo uses So obviously, they balance the bacteria and also fungi and also mottages of go away, and that becomes a problem.
And because the bowels are spastic, these spasm are not propagating. They they don't let the gut move forward. They are essentially useless contract contract contractions as opposed to be coordinating. So this leads to slowing of the bowel transit that leads to constipation very commonly in these patients or the IBS mix, meaning that some days they're constipated, some days they're on the looser side, they alternate. Depending on how much gases in there.
So very commonly, they have IBS mixed type or IBS constipation time. And it is interesting because there is 1 study actually be done by Magnus, a Sembran in the in Sweden that was presented at DDW. That they did very interesting study. Because previously, Mark, Pimentel did show that if you infused methane gas into intestinal looming of dogs. It slows down.
What they what they showed is that in over a hundred and 50 patients and also over 30 healthy controls, those who have elevated methane they give them the a smart bill, which goes in and measures the transit of the gut. And what they showed is that doesn't matter if you are a healthy control or even even our ABS patients, If you have excessive amount of methane, your colonic transit is double the time of somebody who doesn't have methane. Which is actually very fascinating the data that they're showing. And, hopefully, they will publish this very soon. But that was 1 of the fascinating studies that I saw.
So hope that that's kind of at least differentiated at what is intestinal batonage and overgrowth versus small intestinal bacterial overgrowth. Another point that I want to make is that this overgrowth can happen in small bowel, can happen in the colon, can happen in both. So it's not necessarily just in the small bowel, and that's a very important point to a notice. Sorry, I talked a little bit too long on that 1. But there was good data that I can go over as well.
We got an email, but I stopped there and see what you guys think.
Well, I think that's a perfect I wanna know more, but I also wanna ask you about what we were talking before. We hit the record button, which is if it's in the small intestine and it's overgrown also in the large intestine, when we think about people testing the microbiome, prior to your work with masks, there was just stool tests. Mhmm. So what we look forward to in the future? And what are you what are you all doing now about mapping the different microbiomes of the intestines?
Right? Because remember all the tests that we used to do and then not more than 90 percent of the microbiome tests that are being done. Still focuses on bacteria. Right? And just focusing on bacteria, you're not gonna pick up the rkea.
So you need different technique of deep sequencing. On catching them. Now, obviously, shotgun sequencing is now becoming more prevalent and a little bit cheaper, but it's still extremely expensive. That's why a lot of research and research teams including us struggle to find funding to do shotgun sequencing because it's very expensive, does pick up Rkea as well. Maybe I just open up that 1 because it's kind of interesting.
So to 16 s sequencing, when we say 16 s, that's just a segment of the gene of the bacteria. That is very stable throughout the evolution. So no matter what bacteria are out there, they have that segment and it looks like a bar code. And we can look at it and say that, hey, this is in the Klipschialo family. This 1 is in the E.
Coli family. So because you're just looking at a small segment of these bacteria, then it's much cheaper to look at and you can quickly do it. But the problem is that it's just look it's similar to looking at the last names with with ignoring the first names. Right? So you're looking at all the Smiths out there.
So he was like, okay, this person is Smith, but you can go deep enough. Because outside of that stickiness, you have to look to say that, oh, is is this John Smith or, like, Kevin Smith or Martha? Right? So you can go that deep when you have this 16 s. Shotcon is different.
Shotcon looks at the whole genome. Looks at it was like, oh, yeah. Whatever I get, I look at it. That's why it's much more expensive. And much more time consuming.
And in terms of gathering the data and also analyzing the data. So the supercomputers that we use to break these analyze these data is as as just we just got them essentially in the last few years that is now commercially viable. So that's the advantage. But when you have the shotgun, you can go all the way, not to the genus, but even to the strain of the bacteria, what exactly that is. And that's the difference.
But it comes with with 1 issue, though. It picks up the genome of everything, including food that you eat, including yourself, so that it's so there is a lot of noise. So it has introduced a new bioinformatics challenge that you have to denoise the data and take that out. But, I mean, that's just the evolution of medicine that we have to go through. But that's why we're trying to move from 16 s to shotgun, but obviously that's expensive.
But that's a transition that is occurring. So that's that point that I wanted to make about sixiness and deep sequencing. So what's a good news here? The good news is that when you do 16 s, you mostly pick up the bacteria. You can't pick up the fungi.
You can't pick up viruses. You can pick up some of the Arcadia, but not all of them. But now that you're doing shotgun, now there's gonna be a host of new data that are focusing on not just bacteria, but also on different parts like Fungai and Orkea. And more importantly, interaction of these 3, right, along with the viruses, and that will become more complex, but Definitely, that's a bigger picture to look at, and that's that's pretty much the future.
Well, that's exciting. Let's talk about fungus because you brought it up a couple of times. And I know a lot of people in our communities, you know, toy with the idea maybe they have candy to overgrowth. You know, I've tried all the usual treatments for Cboe and Imo, and I'm I even have a negative Cboe breath test or not. And I'm just not getting better.
How often do you feel like a fungus plays a role in that? And if someone's like fungus a fungus, I've never even thought about that, you guys? Like, what is it?
Right. So the whole the concept of fungal growing is mobile. Let's it's not a new 1. It goes back more than half a century. That's interesting enough in the New England Journal of Medicine.
They they quantified how much a fungi exists in small bowel and the large bowel and that's that's amazingly that cut off still holds. So What we showed actually on on this DDW is that we went to the small bowel now we can pick up the fungi now with the new technology. And we did a deep sequencing on them. And long and behold, patients who have more than 10 to the 3 fungal elements in the small bowel do have more abdominal pain. And interesting enough, the the more you fungi that you have, the more actually a a seabull you have.
It was interesting to see that they do actually interact with each other. Not all single patients had excessive amount of fungi, but almost all patients with excessive amount of fungal did have seaborne on top as well, which is fascinating. It shows what we call microbio bacterial interactome, which is essentially the interaction of these 2, which which is definitely interesting. Now in concordance with the previous data, the dominant fungi in the guts belongs to the Canada family. And and I'm talking about plus 90 percent.
Now, Canada, Algonquin, Canada, Colorado, those are the 2 common ones that's that are in there. So so yeah. So there is definitely a concept of small intestinal fungal overgrowth exists. There appears not to be much of a correlation with small intestinal fungal overgrowth and the amount of candidate in the stool, which is not surprising. Considering how much bacteria is in there and how much interactions in there, they suppress the fungal growth in there.
So that's that's the newest sort of approach that is definitely puts ACC4. On the map for future research and target for treatment for sure.
Speaking of target for treatment, do you ever see patients where you're like, I think, you know, even if you didn't scope them, I think you probably have fungal overgrowth. And then do you change the treatment at all? And what would be that indicator to you? That clue that they may have a fungal overgrowth? Howard Bauchner: Yeah, I
mean, 1 of the situation is that, well, breath test is negative. Remember, fungi don't produce hydrogen or methane or even hydrogen sulfide. So I can't pick them up on a breath test. Right? They produce carbon dioxide, but I mean, how am I supposed to pick for carbon dioxide?
Because I'm producing it myself. So it's hard to differentiate a microbial CO2 from human CO2. It's especially impossible. So I generally prefer to do and does scopy and do a small bowel aspirant and do fungal culture and see if I if the patient has small intestinal fungal over good. Because even though it's there, it's definitely less common than Cboe.
The advantage of aspart is that it tells me what type of fungi it is. Right? So because the treatment and the dose of treatment may be different for example, between Canada, Alpiqins and Canada, globally, Canada, globally, is more resistant. So so definitely that's my preferred route. But, you know, you have to be practical sometimes.
You have a patient that is not responding to the usual seabro treatment. And other pro mobility treatment and other other treatment that you have done regarding abdominal pain and abdominal bloating and distension, And that's the time that we may consider temporary therapy, although obviously that's an off label therapy. But after reading out the risks and benefits of the treatments that we use.
Are you thinking like NICE statin? Like, what are some of those therapies? That's what I
was gonna ask. And and specifically, what if you get Candidical prada, which is more resistant? What do you find works for prada?
Yeah. Well so that's that's another interesting that you said because when you have you do grow Candaglibrata, then you ask the microbiology lab, I was like, okay, can you tell me what's this is sensitive to? And even when they say that, okay, for example, it's sensitive to fluconazole. But then they tell you at what MIC. They tell you at what dose.
Right? So, for example, they say that, hey, the usual dose may not work. You need to double or even triple the dose in Canada, glabirata. And so, microbiology lab is able to tell you It's usually filgotosol sensitive, but it needs a higher dose than candidate applicants. And that's that's not something unknown.
We do know that based on the cases of when patients have Canada fungema, when the candidate is in the blood, for example, a threatening of endocarditis. That's that's a well known fact that the physical abirata, need a higher dose of antifungals to treat that.
Well, you know, some people may not realize the scope conversation that we need to reveal here about how you developed that special scope that doesn't get contaminated and all of that. If you could clarify that for everyone because it's it's breaking news, really.
Yeah, absolutely. I mean, because 1 thing that's let's let's talk about how we do ask for it from the small bowel. Right? So you go for endoscopy, you're under anesthesia, So we go with the scope through the mouth. At back of the throat, usually, there is much of a saliva sitting there.
Right? So we actually aspirate that amount of a lot of us sitting there if it's too much and suction it because, well, it can go to your lungs, so we don't want a patient to aspirate that data. Then we go to end today's esophagus if there is, like, a little bit of a gunk and a little bit saliva that is in there, so we suction it. Right? And then we go to the stomach.
If there's excessive amount of fluid again, we suction it. So that as those stuff doesn't come back to your esophagus, go to your lung and you aspirate. Right? So that's a complication that's gonna happen with it. That's gonna be so we counteract that by suctioning whatever we see.
Right? So this leads to that suction channel of Endoscope to be totally contaminated by the time that you get into the small bowel, it's just all gone from the throat all the way to the stomach that is just sitting here. Right? So that such a channel is already contaminated. So if I go into this mobile and suction just with that suction channel.
Obviously, all that stuff is gonna come to that sort of a collection tube that I have. And obviously, when I send it to a microbiology lab, it's going to grow all sorts of things, including respiratory tract bacteria, which the same as gut microbiome, we do have respiratory microbiome, and that's not abnormal if I pick up some of those for example, somehow philosophically pick up. And also, you you know, saliva is also has a lot of bacteria. Strep measures and all that. It's it's that's the native bacteria in the gut.
So the next round of improvement was that, okay, let's send a catheter, a sterile catheter through the channel, that is that there's an open tip, and it goes to the small bowel and let's suction with that. But the problem is that while you're pushing that catheter in and the tip is open, obviously, some of this stuff will go in. So it decreases the amount of contamination, but definitely doesn't eliminate it. Now the second sort of iteration and the most revolutionary report is that Now we have 2 catheters inside of each other, and there is a membrane at the tip. So when we go through first, we go through the small bowel, And then whenever we're in a small bowel, finally, the inner tube comes out and advances into the small bowel and starts suctioning.
And that kind of eliminates the contamination risk. So this was a lot of work. The problem is that when you put 2 plastic tubes, which catheters are made out of. On top of each other, they don't move up. Right?
Now you're inside the scope. You you have a bent scope. It it just doesn't move. Right? So the friction of 2 plastic on top of each other is just doesn't move well.
And it was a lot of engineering that went through that, to make that happen with different types of material going in each catheter, the inner and outer sheet, to make it able for that catheter to slide through that. So that's how we do the aspiration now to decrease the chance of contamination. And that's why some of the aspiration studies in the past when you look at it, don't correlate with breath testing. Well, because they're contaminated. Right?
So Mayo Clinic, for example, just published, Brian Lacey, published paper 2 years ago. That showed that that that single lumen technique has 19.6 percent, 20 percent false positivity rate. So 1 fifth of your samples are like, well, it's saliva, and so it's it's not accurate. So and 20 percent in the world of microbiome, that's a lot. Because that will skew your results significantly.
So you win and this double catheter eliminates that issue.
What are the chances of the double catheter going global? I was talking to a local gastroenterologist here, and I was talking about that he goes, oh, it'd be so great if I had 1 of those, you know. It's not mainstream yet.
Yeah. So again, domain issue is actually making this sort of very delicate catheter, like, a mass producing it. But, hey, I'm not gonna I promise, but I I we will have it unless something goes unusually wrong, commercially available probably in winter 20 24.
Oh, that's fantastic. Yeah. That's fantastic. May I have the name of the catheter?
The catheter, we called it endo Lotus. Because, you know, we call it load a scan through because the way I designed it, at the tip, it has capillary. So the inner catheter has multiple capillary tubes. So I I was inspired by how because if you think about it, how do trees, how do how does the sequoia sucks blood and not sucks blood. Such water from from the ground all the way to, like, whatever it says, 60 m high up, it's through capillaries.
Right? So they they suction and things come up. And small bowel is a very dry, sort of, Oregon, interesting enough especially after fasting that you need to do for endoscopy. So this cap the inner catheter has multiple capillaries just like the the roots of trees and it goes through and it kind of like sucks and wicks that fluid out into the catheter. So that also helps us because sometimes we go in there and it's bone dry.
But we can always wick out of it, which this catheter will be do. So I called it endo, Lourdes. Because, you know, I have you cut the the the roots of Lourdes? It's like those like, they're not the capillary, but there is, like, the air pockets, but it it's actually that's how it looks like at the tip. It looks like a horizontally cut route of the low list.
Well, that's beautiful. Almost like a honeycomb. That's so cool.
Exactly. Yes.
That's so cool.
You know what, Ali, while you're while you're talking about that and about the lineup, the disconnect that had existed between culture testing, the gold standard, which now you've significantly improved. With this technique, and various forms of breath testing. Can you just comment out about a glucose breath testing versus lactulose? And, you know, we see often in the studies that glucose can look better in studies, but in practice, we find lactulose works better. Many of us do.
Can you can you just discuss all this and then the culture lineup and
I can't agree with you more. I think Obviously, people like glucose because the idea is that it does not reach the colon. Right? On the other hand, lactulose has a chance of reaching the colon eventually because it doesn't get absorbed. So you may pick up the cholonic fermentation if you continue the test for a long time.
So it's it was just a battle of specificity and sensitivity of these 2. So 1 main issue was that a breath testing kept being compared to aspiration. And aspiration has 2 issues. Right? So number 1 contamination.
So 20 percent of the times, your gold standard has false positive. So, I mean, that's that's essentially a 10 standard. The second issue is that Aspiration goes and aspirates a 5 to 10 cm segment of the small bowel. Right? So and then we take that sample and try to extrapolate that data to 6 m of small bowel, 20 feet of small bowel.
So that's just naive to think that that's a completely perfect representative sample. Right? So so it has false positive rate because of contamination, and it does have false negative rate because of the sampling error. Right? So that those are the problems with the the aspiration.
You wanna compare that to better thing, obviously, when you compare and try to use sensitivity and the specificity for a test, A gold standard need to exist. And well, a gold standard doesn't exist in this situation. It's just an agreement exists between the 2 And if anything, these 2 tests are complementary rather than 1 of them being gold standard, not the other 1. Not. So now the difference between glucose and lactose.
Now it goes to, okay, how long glucose travels, and how long lactose travels. But the the reason why I think glucose, the research field, and all as it works, but then we it comes to the clinic. I'm, like, I'm like, we're the positive ones, so I get stuck, is I think it's because when we do it in the clinic, patients are fasting. Right. I'll give you an example, for example.
Right? So when a patient is hypoglycemic, what do we do? We give them glucose tablets. Right? And run right away within minutes, the glucose goes goes up.
The glucose gets absorbed starting from the mouth all throughout. Right? So glucose, when it gets absorbed, obviously, the concentration of that decreases significantly. And that is in part driven by the glucose level of that patient that is doing the glucose testing. Right?
And obviously, it's a little bit on the lower side because they're fasting for 12 hours. At or at least 8 hours. Right? So glucose is continuously being absorbed. So 1 big problem with glucose is that as it travels through the small bowel, if it reaches there, it significantly decreases in terms of how much glucose is in there.
So you have no idea, for example, and your judgment on how much your Google is being exposed to the bacteria, which is a problem if you're looking for hydrogen production using glucose. Right? So that's why I think it feels in the clinical practice because it's just at the glucose absorption among patients is highly variable and how much glucose reaches the small bowel and how much of it reaches the gigaenovelum is going to be highly variable. And I think in clinical practice, we need I use laterals. And that's that's the reason why.
Now, it there's a fair criticism to that. That somebody with rapid small bowel transit, then laterals can reach to the colon and then hydrogen production occurs. And you pick up cholonic fermentation as small bowel fermentation in somebody with ultra wrapped small bowel fat. But there are a couple of things that needs to be considered here. The very elegant study was done in 19 89, and we won't be able to do this anymore, is that they used to give catheters with with a weight filled with mercury in them to people.
People would swallow it. And this would travel into the gut and they would do x rays on them until they're like, oh, it's in the CECO. Right? So think about it. I guess that they're sitting in their mouth, they're sitting on all of these.
And it's full of micro if that opens up you you like, you know, things that won't happen again. So what they did is that they put that into the Sequium and they started putting lactulose in it at a rate of 0.15 g per minute. And they just waited to see how long does it take for the hydrogen to go up in your breath. And it takes about 40 minutes for the hydrogen to go up by 20 part per million in the breath even when you're just infusing continuously the lactulose in the sickle. So that just tells you that there is a lag between exposure of the lactulose to the bacteria even in an area that is nuclear amount of bacteria is just sitting there, like the Sebum, that takes that much time to produce hydrogen.
So that's why 40 minutes is there. Right? And unless your small bowel transit is like 10 minutes, think about it. It's it's 20 feet. Right?
So if for something to go through a a lumen in 10 minutes of and that lumen is 6 m is that's that's like that's very fast. Is it possible? Yes. It is possible, but it's rare. And so you're not gonna get those false positive, a test.
So I think the thought of false positivity of flatulence is a little bit exaggerated And that's why I just used the actualism and clinical practice. And then I think you do too because otherwise, I think I'm gonna miss a lot of placebo patients that otherwise will get to the next doctor and get an empty person's baby. Right? So -- Yeah.
Yeah. If it happens. Yes.
Okay. I have it.
Your question can yeah. We've spoken
to lots ago. Okay. I have another question for you, Ali. Sorry. I'm adjusting my light.
The sun is streaming in here. 1 second. Okay. So on 1 of your studies, There was something that was just, you know, tucked away in there, 1 sentence that came out DDW, that was a bit shocking, and that I'd love for you to talk about, and that is that you identify lactobacillus as a small intestine microbiome disruptor.
Yes.
In 1 of them.
It was a surprise to me too, so I don't know what to tell you. So because, you know, traditionally, we can't liked the business as the healthy guy. Right? So like something that you can find in yogurt, something that you can find all over. Right?
So I mean, the role of for example, lactobacillus in vaginal microbiome is it's like it's proven. Right? So but, you know, there's a difference between gut microbiome, and marginal microbiome, especially in the certain terms of PH. Right? So that's actually a prime example of 1 bacteria being helpful in 1 area.
It's not necessarily helpful in other areas as well. So what we saw essentially and read it, this is an association, meaning that we saw that ventricular bismuth was going up the network of bacteria are breaking. So network of bacteria is that, well, it's a volume firmmatic sort of like a design. Essentially, it looks at interaction of multiple bacteria. And builds of a complex network.
And the complexity of the networks is counted similar to any other network by how many lines how many dots are there that we call nodes, and how many lines lines are connecting these nodes together. So the complexity of this network significantly when it was reduced and people who have excessive amount of lacto bacillus to our surprise. So now it is possible that there is somebody else that is decreasing everything, including the network and pushing the ad like to be sold us up. I don't know. But definitely, there was this association that be observed, but that's 1 thing that we keep we need to keep a look out to see if gets this gets produced in future studies.
Howard Bauchner:
Yeah, because, you know, we have so many studies and even patients who do take lactobacillus orally and
-- Right. --
get benefit, not everybody has. But, you know, so even people with Cboe. So It's like what, you know, I think what patients may do when they hear about this is they may go, oh my gosh, I have to stop taking acid off like of still sassadopoulos, you know?
Yeah. Yeah. I I don't think we're there yet. It's just, obviously, any discovery happens at 1 point and then needs to be reconfirm and then further down. And remember, like to be such a family, it's it's not like a tiny family.
Right? So they there's ton of different strains. And I wouldn't be surprised that some of them are hurtful and some of them are harmful. So this is not at a point that you would make any clinical recommendation based on. This is just a finding.
Great. Thank you for clarifying that. Okay. And then another 1 that was interesting was that you found Well, well, you've been able to identify Chlebsiella as 1 of the main overgrown bacteria in hydrogen sebum. And I was fascinated that in 1 of the studies you found that even when it was present at subsea levels, that it was involved in pathology,
Right.
And if you just talk about that, that would be interesting.
Yeah. Absolutely. So and and again, this goes back to your point about disruptors. Right? So they are literally bullies in the monkey microbiome just like when you have bullies in the school.
So And so 1 bully can disrupt the whole school as opposed to a few calm guys that's just behaved abnormally. So that's essentially the same thing. Cobsiella, they they they do have the capability of affecting the phone guide. The other bacteria, they produce biofilm, so they mess things further up. And now there is data even emerging that they can affect the permeability of the gut.
So essentially, they they can wreak a havoc in the small bowel. And on top of it, they produce a lot of transmitters. Right? Classic production of histamine by Klipschia is a problem. Right?
So that's that's 1 thing. So they can even have systemic effects, these bacteria. And that's obviously and that's why I was saying that it's exciting times. Because now if you're instead of, like, talking about, like, big groups of bacteria, now we're getting focused and focused and focused and focused on different specific disruptors and see that if we can suppress those and that would be enough to regain the microbial balance. Because I think about it, the more tailored and more precision that we have there, we can have more precision medicine therapy for that approach as opposed to empiric sort of, for example, antibiotic therapy.
So that's that's why it makes it very interesting. And also, it is it makes it possible that, okay, I found this specific bacteria. Let's see what it produces that it can suppress rather than killing it. To make the balance better. So that's obviously another sort of interesting door that it opens.
Howard Bauchner:
Have you been look you've been looking into those kinds of treatments?
Well, no, I think about it this way. Right? So that there is, for example, histamine, right, that is being produced. So should be a target interluminal history. So that's 1 pathway, right?
Serotonin as being produced by a lot of bacteria. Should we target intra lumen and serotonin. Having said that, that's easier said than done, suppression of interluminal biomarkers is extremely hard because no medication is just gonna get distributed evenly throughout the guts. Right? So that's a problem, but those are those that are being open as potential therapeutic pathways.
Well, on that node of treatment, can you just share with us what antibiotics or antibiotic combinations you're currently using for the different types of Cboe and EMO?
So, antibiotic use, I mean, in practice and to be pragmatic. So antibiotic use is obviously driven by many factors. Right? Patients patient preference and obviously testing the results and also patient symptomology. And sadly enough insurance.
What gets covered? What doesn't get covered? Right? So that's that's that's that's that's real life. Right?
So for treatment of somebody who is treatment naïve of placebo, novo antibiotics in the past. I definitely reach for refaximin first, which I think is the safest drug that is outer and it's it has very little systemic absorption. And the safety of it, if you know it from hepaticizumab, but the IBS trials that is at this very good. The problem costs. Right?
So that's that's 1 issue that we have with it. But, you know, that's the ideal world. Right? So that's that's what I reach for. Other treatments for hydrogen predominant bacterial overgrowth.
I used to use a super flococicin a lot. But the problem with superefloxacin is the black box with the arthritis that can happen. It's rare, but when it happens, it does have That's a problem. Right? And because of that, I I do use dot Cycline as 1 of my other options that I use.
There is data on metronidazole as well, but you know metronidazole again. It's not a well tolerated medication. Some people get nauseated with it, but although a lot of people do tolerate that. So Those are some of the options that I use. In terms of email, obviously, we target hydrogen production So the metastages are not capable of producing methane, and then we target metastages themselves.
So you need some something to suppress the hydrogen production, something similar to rifaximin, and then something to suppress methanogens. So Neomycin is 1 option. There was some shortages in Neomycin, so we had to switch to fragile. But now, actually, Neomycin is becoming more available, which is good news. I like me on my end because it's, again, fully observable.
You know, whenever we we can avoid systemic absorption of the antibiotic. I think you should do it for sure, avoid so because that's more of a tailored management. So essentially, my treatment becomes refaximin plus a new mysine. If refaximin is not an option, then I have tried Profluidial as a combination, also have tried augmenting as well, which is essentially amoxaceline and globalic acid together. So that that does have an effect on both of them.
So those are the treatment. When it comes to hydrogen sulfide, I I do try a rifaximen. I do come sometimes combine it with bismuth. If patient is not constipated or, like, doesn't get constipated with business. Some people are sensitive to business.
You just get really going to be. But there is data that it does suppress the hydrogen sulfide. So I I saw that those very slow because I don't know some people are very sensitive to a bismuth. Bismuth tablets come and absorb those of 262 mg. So so I usually try 1 tablet twice daily and work my way up to see what's because, you know, I don't want the patient to say that.
Well, thanks for fixing my diarrhea, but I haven't had a bowel movement for weeks, so that's not a good outcome. So that's that's that's how I approach it.
I see. Yeah. That was great.
That was amazing, bitch. Well, of course, a page full. But I'll I'll I'll
I'll limit it.
Okay. There's 2 more I just really wanted to get to. And we may only have time for 1. So I know you all did a study on artificial sweeteners, and I know a lot of our patients are very interested in that. And if I mean, just briefly, I know the description was you took folks who use carbohydrate based artificial sweeteners and then versus aspartame, which is non carbohydrate.
Can you just tell us anything about it? I mean, I'm a little concerned people are going to go, oh, no. Can't use the sweetener that. And I think again, we're not there yet. So
Yeah. So we're definitely not there yet. So remember, Probably, you've looked at the literature, artificial suit suitings are kind of under fire in multiple, sort of, like, fields and filled in the chronology, and of aging, a field of diabetes. And so remember, people who take artificial sweeteners, they're taking it for a reason. Right?
So because of that reason, it's not really whether it's because of obesity, it's because of diabetes, it's because of, like, other medications that they're on. And for that reason, their macro bottom is already different because they're different from the others. Right? So so that's 1 thing to to look at. Because for example, there were, like, studies that show that, okay, for example, coffee improves morality.
Essentially, you know, the multiple studies that show that in animals of internal medicine. But if you sweeten that coffee with, like, more than a drink, a tablespoon of sugar or you use artificial sweetener, that that effect goes away. But the thing is that all, okay, who puts artificial sugar in their coffee somebody who wants to avoid calories. Right? So because of that, well, of course, if you compare a diabetic versus a non diabetic patient, the rates of mortality because of heart disease is gonna be different.
Right? So it's not because of that sugar or that artificial sweetener specific. Right? So, but what's interesting is that these studies try to get rid of these compounders as much as they can, but it's never a hundred percent. So so that's why I think you're not there in terms of saying that, oh, no, do not touch any artificial sugars because because they cause all sorts of troubles.
We're we're at least from the gut microbiome standpoint. And these these are just hypothesis generating sort of studies and findings that sort of instigates further studies to see whether these are true or not. These are again not at the level that we make clinical recommendations.
Howard Bauchner: All right. Thank you. Yeah. Allison, I hate to do it, but we have to know we gotta wrap up. We gotta wrap up.
Thank you, doctor Seaburger, for the excellent questions and co hosting with me. Thank you, doctor Rezai. We really appreciate you Godspeed and your works, sir. We're praying and sending good vibes to everyone over there. And
we really do so much for all the work you do and all the answers to these questions.
Alright. You're welcome. Anytime.
Oh, good. You said anytime, Allison. Anytime. Can we meet with you after ACG in the mall?
Yeah. Sure. Volkswagen Uber? Alright. Okay.
Alright. Alright. Send our best to everybody. Thank you so much.
Thank you. Bye.
Bye bye. Bye. Else, and I'll see you in 04:15. Got it. Okay.
Great job.

Hosted by Shivan Sarna and Dr. Allison Siebecker.

Highlights from this 50-minute session:

  • Is Lactobacillus a disruptor of the small intestine microbiome?
  • Testing - lactulose vs glucose breath testing vs the gold standard (culture)
  • Endolotus apparatus and what you need to know
  • SIFO - treatment for resistant cases
  • What treatments Dr. Rezaie uses for the three different types of SIBO/IMO
  • Methanogens, methane gas, and their impact on smooth muscle and healthy people

Check out Drs. Pimentel & Rezaie's book, The Microbiome Connection, which is available in the United States on Amazon and all major booksellers. If it's out of stock, grab the Kindle version.

The Microbiome Connection



🧾 SHOWNOTES

Shivan Sarna's Healing SIBO: Fix the Real Cause of IBS, Bloating, and Weight Issues in 21 Days
👉 https://sibosos.com/book 

Join the SIBO Recovery Roadmap Course® here (for Patients): 
👉 http://sibosos.com/sibo-recovery-roadmap 

Dr. Allison Siebecker's SIBO Pro Course (for Practitioners only):
👉 http://sibosos.com/procourse 

Watch our FREE videos on YouTube!
👉 https://www.youtube.com/c/SIBOSOS 

Join us in the SIBO SOS®️ Facebook Group:
👉 https://www.facebook.com/groups/SIBOSOSVirtualSummit/ 

Support Dr. Mark Pimentel's Gut Microbiome Research 
👉 https://support.cedars-sinai.edu/fundraiser/2127909 

Dr. Allison Siebecker's FULLSCRIPT Dispensary 
15% off 20,000+ professional-grade supplements

🛒 https://sibosos.com/fullscript 

Dr. Allison Siebecker's Rupa Labs Functional Testing Library
🧪 https://sibosos.com/rupa 

Trio-smart™ is the only breath test to measure all three gases: hydrogen, hydrogen sulfide, and methane. Available from Gemelli labs which you can order for yourself by filling out the questionnaire.
https://www.triosmartbreathtest.com/

The IBS Smart Test. A simple antibody blood test that is making IBS easier to accurately diagnose... and revealing the root cause behind the disorder! (You may have heard of it if you follow Dr. Mark Pimentel's groundbreaking research.
https://sibosos.com/ibs-smart-test


// ABOUT

Dr. Ali Rezaie is the director of the motility center and the Bioinformatics and Biotechnology at MAST program at Cedars-Sinai. Dr. Ali Rezaie researches irritable bowel syndrome, motility disorders, inflammatory bowel disease, and population-based data analysis. He has published over 100 research articles in peer-reviewed journals, including Gastroenterology, American Journal of GastroenterologyDigestive Diseases and Sciences, and Canadian Journal of Gastroenterology. His works have been cited more than 8,000 times by other scientific journals. Dr. Rezaie serves as the associate editor of the Journal of Digestive Disease and Sciences.

Shivan Sarna is the author of Healing SIBO, TV host, and the creator of the SIBO SOS® Summits and Community, the Digestion SOS® documentary series, the Gut & Microbiome Rescue Summit, the Lymphatic Rescue Summit, the Dental-Health Connection Summit, and Chronic Condition Research, a 501(c) 3 non-profit to further research under-funded medical conditions. After a lifetime of struggling with health issues, Shivan made it her mission to demystify her own health struggles - and to share that information with others who were struggling. Her special skill is finding and connecting with the leading expert doctors and connecting those experts with the people who need their help. Her personal mantra is SOS: Save Our Selves, and that's what she has helped thousands of people do! 

Dr. Allison Siebecker is an Instructor of Advanced Gastroenterology at NUNM, an award-winning author, and the 2021 Lifetime Achievement Award recipient from the Gastroenterology Association of Naturopathic Physicians. She was the former medical director and co-founder of the SIBO Center for Digestive Health at NUNM. Dr. Siebecker has specialized exclusively in SIBO since 2011, serving as a second and third-opinion referral doctor for patients who have failed previous treatments and is the creator of many staple SIBO treatments. Dr. Siebecker is passionate about education, she has been teaching physicians, medical students, and patients internationally since 2010, with many going on to become SIBO specialists and teachers, sharing alongside her at conferences and in their own courses, websites, and books. www.siboinfo.com

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