SIBO updates with Dr. Ali Rezaie at the Functional Medicine Discussion Group Meeting

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Dr. Ali Rezaie discusses Updates on SIBO and IBS with Dr. Ben Weitz at the Functional Medicine Discussion Group meeting on August 25, 2022.

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Podcast Highlights

4:00:  For years the definition of SIBO was bacteria count of 10 to the five cfu/ml or more, meaning that more than a hundred thousand bacteria in the small bowel.  But that was based on the data from the blind loop diseases from the 50s and 60s.  But what Dr. Rezaie and Dr. Pimentel have shown in the North American consensus and in the SIBO guidelines is that the cutoff is 10 to the 3 cfu/ml or 1,000 bacteria.

5:46:  Bacterial overgrowth is not an infection, but rather it is essentially a dislocation of colonic bacteria into the small bowel.  And Intestinal Methanogen Overgrowth (IMO) can happen in the small bowel, or the colon, or both, so it’s not necessarily a type of SIBO, because it’s not just small bowel related.  In the colon you have about a trillion bacteria/ml and in the mouth it’s about 10 to the 9 ml. 6:47  The way the bacteria count is kept low in the small intestine is with the housekeeper waves or the migrating motor complex phase three.  These peristaltic waves occur every two hours and they start from the beginning of the small bowel and go all the way to the colon and last in each segment for 5 to 8 minutes. Stomach acid is also important in reducing bacteria but less important than we thought it was in the past.  There are patients who have gastrectomy–have their stomach removed–who do not get SIBO because their housekeeper waves are normal.  Digestive enzymes and having an intact ileocecal valve can also help to keep bacteria counts low in the small intestine. There are patients with Crohn’s disease who’s ileocecal valve is removed and they do not get SIBO because their housekeeper waves are normal.

8:40  Causes of SIBO.  SIBO is a secondary and not a primary disease.  The causes of SIBO include a postsurgical blind loop. Adhesions resulting from either surgery or from endometriosis.  Any medication that slows down the gut, such as narcotics or anticholinergic medications, can cause SIBO. Chronic pancreatitis, because the pancreatic enzymes are not being produced, is very commonly associated with bacterial overgrowth.  Small bowel diverticulum is often associated with SIBO.  The most common cause is small bowel dysmotility, which can happen in the setting of connective tissue disease, diabetes and in the setting of post-infectious irritable bowel syndrome or post infectious anti-vinculin antibodies.  The most common bacteria involved in post-infectious IBS is Campylobacter, but E. Coli infection can also cause this and this affects the enteric nervous system, which affects the motility of the gut.  Also, whenever there is inflammation in the small bowel, such as in the case of Crohn’s disease or after radiation, you have an increased chance of SIBO.

10:30  Proton pump inhibitors (PPIs).  It is commonly thought that proton pump inhibitors cause SIBO by blocking HCL, but while some smaller studies seem to show this, the larger studies are negative and Dr. Rezaie believes this is because PPIs do not change the pH of the small bowel.  This is because when the chyme, which is a mixture of food with acid, enters the small bowel it gets neutralized by bicarbonate within 5 cm of the pylorus.  So PPIs do not change the small bowel microbiome.

12:29  The symptoms of small intestinal bacterial overgrowth include abdominal distention, bloating, esp. post-prandially, abdominal discomfort or pain, fatigue, brain fog, diarrhea and urgency, which is more common with hydrogen and hydrogen sulfide producing bacteria. Or they can have constipation, which is more common with IMO (methane producing archea), but there is some overlap in such symptoms and you see patients hydrogen sulfide bacteria that have constipation and patients with IMO who have diarrhea.  They can also have weight loss or weight gain.

13:25  The pathway of gas production shows that carbohydrates break down into carbon dioxide and hydrogen and that hydrogen can be used by archea to produce methane. Bacteria can produce acetone from hydrogen. They can produce hydrogen sulfide and they can produce nitrates. Our cells do not produce hydrogen or methane, so any hydrogen or methane found in the body is produced by the gut microbiome.

14:08  Patients with high methane (IMO) are 3 1/2 times more likely to have constipation and the higher the methane levels the more severe the symptoms are, esp. the bloating and abdominal distention since higher methane slows the GI transit more.

14:58  Diagnosis of SIBO.  The gold standard for diagnosis is small bowel aspiration.  But this can only diagnose hydrogen SIBO, since the methanogens that cause methane SIBO cannot be cultured after aspiration. So for diagnosis of IMO we have only breath testing. One of the problems with small bowel aspiration is that you have at least a 20% contamination rate of picking up some bacteria as you pass the scope through the mouth, the esophagus and the stomach on the way to the small bowel.  Dr. Rezaie and Dr. Pimentel have developed protected catheters that eliminate this contamination rate and increase the sensitivity and specificity of small bowel aspiration, that should be commercially available by next year.  The other problem with small bowel aspiration is that you can only sample the proximal section of the duodenum, which is the first part off the intestines and this does not properly represent the whole 20 ft of small bowel.

17:58  Breath Testing.  The way breath testing works is that as food goes into the small bowel, if there’s excessive bacteria, the carbohydrates in that food will be fermented and the gas that is produced will go into the lungs where you breathe it out.  Among the pros of breath testing is that it’s noninvasive and it can assess a longer segment of small bowel as compared to aspiration. By identifying hydrogen from methane from hydrogen sulfide producers, it allows providers to tailor the most effective antibiotic therapies.  Among the cons of breath testing is that if you have overgrowth of non-fermenting bacteria, then this will not be detected.  If you have ultrafast transit, such as occurs with some neuroendocrine tumors, the sugar will get to the colon quickly and you will miss SIBO.

21:09  For Lactulose breath testing the specificity is 85% and 95% in centers where they carefully control the diet 24 hours before and they calibrate their machines correctly. Glucose breath testing is more specific but less sensitive than lactulose breath testing.

21:50  There are asymptomatic healthy controls who test positive for SIBO with breath testing.  The conclusion is that they have asymptomatic dysbiosis.  One study by Allegretti, et al. showed that of people who received a fecal microbial transplant for a C-diff infection, some end up with IBS symptoms after.  If the FMT donor was breath test positive for SIBO, the chance of getting those symptoms was 50% as opposed to if the donor was breath test negative, which was 14%.

23:45  When we look at how to interpret a lactulose breath test, for it to be positive there has to be a rise of hydrogen of more than 20 parts per million prior to 90 minutes.  For glucose breath testing, they are proposing to change the level at the next North American consensus to a rise of 12 instead of 20 to be considered positive for hydrogen.  This 90 minute cutoff correlates with small bowel aspiration deep sequencing data, which shows that proteus bacteria are very abundant and firmicutes are very low.

So for methane though it’s the cutoff is well established. The cutoff is 10 part per million. And this is, as I said, it can be the small bowel or the column. So you don’t look at the rise, you look at an absolute number and this 10 port per million, it’s interesting that it also, it works both for glucose and lactose. And this is a paper we just published I think about six months ago, that it works both for glucose and lactose and also correlates with constipation gas and less diarrhea. More importantly, it correlates with the load of methanobrevibacter smithii, which is the main archaea in our body that produces methane and also positivity remains stable on repeated measurements if you don’t treat the patient. So that’s very important. Because one argument is that well is method is just a sign of a slow transit.

Well I mean the answer is not, is no because sometimes we give antibiotics to somebody with IMO and [inaudible 00:27:26] and methane drops and patient has less symptoms. So it’s not just a matter of trans. And another very cool thing that we showed is that if you treat the patient for 14 days and you measure methane every day, a fast methane and it’s actually very nicely you see a drop in the methane levels of with antibiotic therapy. This is very important because for example, if I see a patient that now after seven days responded to therapy, then next time that I treat patient I will do it for seven days. I won’t do a 14 day course. On the other side, if I see that okay on the day 14 a methane is still elevated, that means that I’m using the wrong antibiotic. So I will use a different antibiotic to or whatever modality you want to use the plant-based antibiotics or you want to do elemental diet. But regardless, whatever you did, you need to switch gears.

So how do you manage bacterial overgrowth? Essentially we think of it as three pillars. Number one is that, is there a modifiable underlying cause that you can get rid of in, for example, is there narcotics onboard and can you get rid of it or can you give antagonist to narcotics? Can you decrease the amount of inflammation in the small mouth? But unfortunately not many times you’ll find a modifiable cause of SIBO. So you need to do induction of remission, which you can do antibiotic or elemental diet or you can do maintenance of remission. That essentially includes diet MMC, sort of modulating drugs that people talk about and also counseling the patient regarding recurrence.

Dr. Ali Rezaie is a world renowned gastroenterologist and researcher with a focus on IBS and the gut microbiome. He’s the Medical Director of the GI Motility Lab at Cedars-Sinai Hospital. Dr. Rezaie has published over a hundred scientific articles in peer review journals and his works have been cited more than 6,000 times by other scientific journals. He’s also the Associate Editor of the Journal of Digestive Disease and Sciences. And Dr. Rezaie is a co-author, along with Dr. Pimentel of the new book, The Microbiome Connection: Your Guide to IBS, SIBO and Low-Fermentation Diet.

Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss and also 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:            Good evening, this is Dr. Ben Weitz and thank you for joining the Functional Medicine Discussion Group meeting. And tonight we’ll be speaking with Dr. Ali Rezaie, and he’ll be giving us an update on some of the latest research on small intestinal bacterial overgrowth, which is believed to be the main cause of irritable bowel syndrome, which is the most common gastrointestinal condition. Thank you for joining the Functional Medicine Discussion Group this evening. And I want to thank our sponsor for this evening, Integrative Therapeutics. So, Integrative Therapeutics is one of the few professional brands of supplements that we use in our office and they have several excellent products that can be beneficial for SIBO.

The first product I’d like to highlight is the Physicians’ Elemental Diet. And the Physicians’ Elemental Diet is a great way to starve the bacteria involved in SIBO. We have several different strategies for getting rid of SIBO. One of them is to kill the bacteria with antimicrobials or antibiotics. Another strategy is to starve the bacteria. And the Physicians’ Elemental Diet is food, essentially, that’s in the most elemental broken down form, so your digestive system essentially can rest. It doesn’t really have to work to digest any of the food. And another product I’d like to mention, is a product that they have, which is called Motility Activator, which is my favorite natural pro-kinetic. And I’m sure Dr. Rezaie will mention the fact that a big part of SIBO is decreased intestinal motility. So to reset the migrating motor complex in a natural way, Motility Activator is a great way to do that.

One more product I’d like to mention that you might not think of that can be very beneficial for SIBO, is Theracurmin. Theracurmin is their highly absorbable form of curcumin. One of the things that happens with SIBO, and I don’t know if this is something that Dr. Rezaie will mention, but some of the data indicates that you get a gut hypersensitivity. And that hypersensitivity increases the symptoms and curcumin is an excellent way to downgrade that gut hypersensitivity.

So now I’d like to introduce Dr. Ali Rezaie, who is a world renowned gastroenterologist and researcher with a focus on IBS and the gut microbiome. He’s the Medical Director of the GI Motility Lab at Cedars-Sinai Hospital. Dr. Rezaie has published over a hundred scientific articles in peer review journals and his works have been cited more than 6,000 times by other scientific journals. He’s also the Associate Editor of the Journal of Digestive Disease and Sciences. And Dr. Rezaie is a co-author, along with Dr. Pimentel of the new book, The Microbiome Connection: Your Guide to IBS, SIBO and Low-Fermentation Diet. Dr. Rezaie, you have the floor.

Dr. Rezaie:          Okay. Do you see what I’m presenting?

Dr. Weitz:            Yes.

Dr. Rezaie:          All righty, perfect.

Dr. Weitz:            Good.

Dr. Rezaie:          So I’m going to give a talk and I’m going to leave some time for questions and answer at the end, because there’s a lot of things about SIBO that you can’t just fit into a talk. I’m going to talk about SIBO, I’m going to talk about IMO and how to diagnose and treat both, essentially. For small intestinal bacterial overgrowth, one important thing is, what is the actual definition? For the longest time, the definition was 10 to the five, meaning that more than a hundred thousand bacteria in the small bowel.  But that was based on the data from the blind loop diseases. Before we had PPIs and we couldn’t control peptic ulcer disease. The only way to control a refractory ulcer was surgery. And one of the surgeries that we used to do, was Billroth II. Essentially, you take, similar to gastric bypass, you take the stomach out of the luminal continuance and that obviously left the bowel to have a blind loop. And bacteria overgrew in that area and that’s what we called it blind loop syndrome at that time. And this is from ’50s and ’60s.  At that time the cutoff that was chosen was 10 to the five, mostly because we used 10 to the five for UTI too. So they just said, “Okay, let’s use the same thing.” But after multiple healthy controlled studies that were done, it’s clear that having a thousand or more bacteria per ML in the small bowel, and granted that the aspiration is not contaminated, is the abnormal cutoff. What has been now shown that we showed in the North American consensus and also in the SIBO guidelines, that the cutoff is 10 to the three or 1,000.

Another thing is that, okay, bacterial overgrowth is not an infection. It’s essentially dislocation of colonic bacteria into the small bowel. And then talking about the intestinal methanogen overgrowth here as well, is that intestinal methanogen overgrowth can happen in the small bowel, or the colon, or both. So it’s not necessarily a type of SIBO, because it’s not just small bowel related. So that’s a disclosure. Another important thing here, is that if you look at the colon here, we have about a trillion bacteria per ML in the colon. And also when we look at the mouth, it’s about a billion, about 10 to the nine per ML.

And it’s fascinating that the small bowel has less than 1,000. The way it keeps itself clean, is through mainly housekeeper waves or migrating motor complex phase threes, which are the sweeping waves that start from the beginning of the small bowel, sweep through the small bowel and get all the way to the colon. And that cleans the small bowel from the excessive amount of bacteria. And they occur every two hours and they last in each segment for about five to eight minutes.

Also, stomach acid is important, but more and more we are understanding it’s not as important as the housekeeper waves. And in fact, we do have patients with gastrectomy, that as long as their small bowel is functioning well, they don’t get SIBO. The most important factor remains the housekeeper waves. Obviously, anti-bacterial effects of bowel and pancreatic excretion is also a factor and also the role of ileocecal valve as well. And again, we do see a lot of patients with Crohn’s disease, whose ileocecal valve is removed, but they do not get SIBO, simply because their housekeeper waves are normal. Meaning that again, when you have a normal housekeeper wave, you can essentially out-power the other defense mechanisms.  We do add traditional manometry and this is a high resolution one, that we place it into jejunum and we look at these contractions that you see. That the contractions happen about 11 times per minute and they last about five to eight minutes in each segment of the small bowel.

So there are a lot of causes for SIBO and it’s important to remember it’s not a primary disease. It’s a secondary disease that can happen in a setting of postsurgical disease that we talked about, the blind loop. And also, adhesions very commonly can happen. Adhesions can happen in the setting of the virgin abdomen, meaning that somebody who hasn’t had an abdominal surgery in the past.  The most common cause of that is actually endometriosis.  Any medication that slows down the gut, such as narcotic and anticholinergic medication can do this. Chronic pancreatitis, because the pancreatic enzymes are not being produced, is very commonly associated with bacterial overgrowth. And also small bowel diverticulum, fibrous bands, they are very commonly associated with SIBO. The most common cause, though, is essentially small bowel dysmotility. This can happen in the setting of connected tissue disease, diabetes, very commonly in the setting of post-infectious irritable bowel syndrome or post-infectious anti-vinculin antibodies.  So the most common cause of this is Campylobacter, but it can happen in the setting of E. coli as well. What happens is that these anti E. coli antibodies, they affect the motility of the gut by affecting the enteric nervous system, and then the migrating motor complexes become infrequent or sometime completely absent. So whenever there is inflammation in the small bowel, same story, you can have a super imposed bacterial overgrowth.

So how about the PPIs? So if you look at the literature, it’s actually quite, it’s [inaudible 00:10:41] to a fact that PPIs don’t change the small bowel microbiome. There’s some positive studies, but the bigger studies are actually negative, which is interesting and it’s probably because of the fact that PPIs do not change the pH of the small bowel. Within minutes the chyme, which is a mixture of the food with acid enters the small bowel that gets neutralized by pancreatic bicarbonate within five centimeters of the pylorus and no matter what the pH of that chyme is, the pH of the Duodenum remains constant at around five and a half to six.  So probably that’s one of the reasons.  Having said that, yes in somebody who has other comorbidities, even suppression, yes PPI can cause trouble, but generally speaking we are not seeing that a type of abnormality.  And I mean if you look at the deep sequencing data, you can see that it’s almost a perfect overlap between people who are on PPI and not on PPI, even based on culture.  It was not different.  But nevertheless, I guess what this points at is that as long as you have a healthy housekeeper wave, then you are good.  And our focus mostly should be on restoration of the bacterial balance and next restoration of moderate and motor complex is to help these patients. 

So these are the symptoms you’re all familiar with.  The symptoms of bacterial overgrowth.  Most common thing are abdominal distension and bloating and obviously post-prandially.  Generally they’re the best in the morning and as the day goes on they get worse. They have fatigue, they have post-prandial brain fog.  They can have weight loss, weight gain, they can have diarrhea and urgency, which is more common with hydrogen and hydrogen sulfide like producing bacteria. Or they can happen to have constipation which is mostly in the setting of IMO. However, these are not universal rules. You’re going to see patients with IMO who have diarrhea, you’re going to see patients with hydrogen SIBO who have constipation. So it is just that people with IMO have a higher chance of getting constipation. That doesn’t mean that every IMO patient is constipated.

So this is a simplified pathway of gas production by microbiome. So the first step is as simple as you can put it, is that carbohydrate breaks down into carbon dioxide and hydrogen and that hydrogen can be used by archea to produce methane. They can, bacteria can produce acetone out of it, they can produce hydrogen sulfide and even produce ulcers. Remember our cells do not produce hydrogen or methane. So any hydrogen or methane found in our body is produced by gut microbiome.  So this is essentially what I was saying. So patients with IMO have three and a half times more likely chance of having constipation as compared to people who don’t have IMO, what tells you there is that, well IMO not every patient has constipation. Another important thing about methane is that the higher the methane, the more severe the uploading and abdominal distension. Another important thing is that methane like hydrogen is a hack, is an active gas transmitter, meaning that by itself it has physiologic effects. So if you infuse methane into the small bowel of dogs, it decreases the transit by 70%.

So how do we diagnose it?  So obviously the gold standard is small bowel aspiration.  So right off the bat, this is not for diagnosis of IMO.  We can’t culture methanogens at this point except for very specialized labs.  So for diagnosis of IMO, we are only left with breath testing. This is for diagnosis of non methanogenic bacteria in the small bowel. So what are the advantages? The advantages is that well antibiotic you can do the antibiotic sensitivity on whatever you culture and you do very directed therapy.  Also a diagnosis SIFO, which is commonly happened with small intestinal bacterial overgrowth. So in that scenario you obviously treat the patient for both. The problem is that we have 20% chance of contamination rate and that’s the data coming from ao.  But the problem is that this is done by the usual single lumen catheters that we do through the scope.  So you put the scope down through the mouth into esophagus, stomach, then small bowel.  While going through that the suction channel of the scope gets contaminated by the oral mucosa and also whatever stuff is in the stomach and the esophagus. So when you put a single lumen that the tip is not protected, some of that stuff goes into the catheter and you culture that as if it was in the small bowel and you aspirate from there. So you get contamination rate. So if you use those rudimentary catheters then you get 20% contamination rate.  Well hopefully next year there will be protected catheters available, not hopefully, there will be protected catheters available that will increase our sensitivity and specificity of small bowel aspiration.

Another issue is the sampling error.  So you’re sampling like 5 centimeters of small bowel and you’re hoping that that kind of represents the whole 20 feet of small bowel.  Well it won’t.  So there’s a sampling error there.  So there is that problem as well.  And we can’t culture all the bacteria and also it’s invasive and time consuming.  Okay, so as you can see it’s even though it’s called gold standard, it’s almost silver because it has some deficiencies.  And at the bottom is the catheter that I was talking about and these are the catheters that we are using right now.  What is still only at the research level.  So we don’t have contamination rate at our center. 

So breath testing.  So breath testing, essentially it’s when the food goes into the small bowel, if there’s excessive bacteria in there that gets fermented, the gas goes into the lungs and then you breathe it out. With the same concept, you could give glucose and lactulose and just monitor the levels of artificial methane that happens every 15 minutes to see if there is excessive amount of bacteria in the small valve. You also do measure zero two, adjust to or you are able to standardize each breath sample based on the alveolar level.  So what are the pros here?  Well it’s noninvasive. It can assess a longer segment of small bowel as compared to aspiration.  It’s hydrogen and methane are exclusive bio markers of microbiome and also it tailors antibiotic therapy as we will talk in the next few slides.  And also predicts response to antibiotic therapy.  So these traits are not found in the small bowel aspiration. Okay what are the cons?  I mean if the bacteria that is causing trouble is non-fermenting, which is not common but it does happen, then you can miss it out obviously. Sometimes if you have ultrafast transit such as like things go through your small bowel within 15 minutes in the setting of some neuroendocrine tumors, obviously you the sugar gets to the colon quickly and you miss it. One important thing is that the sugar gets to the colon, it takes 40 minutes, takes 40 minutes for the bacteria that is exposed to that sugar in the colon to produce a hydrogen to a level that is 20 parts per million detected in the breath.  So there is a lag there. The reason why I’m saying in this is that as some use a Scintigraphy to criticize a breath testing and saying that well by the time that 5% of the, and the medium is in the colon while 95% of the small bowel, now we are seeing a rise in the breath hydrogen. So this is coming from the [inaudible 00:20:37] from that 5%. But that’s a little bit of a flawed theory because well first of all, 95% of that medium is still in the small bowel. Number two is that the bacteria in the colon takes 40 minutes to produce hydrogen to be detected in breath and Scintigraphy does not account for that lag. It’s not an immediate phenomenon.  And because of that we use the 90 minute mark for the overgrowth.

This is a healthy control sort of study that we did while back on more than like 800 asymptomatic controls. So overall the specificity about 85%. But if it’s done in centers that they know what they’re doing, it’s about 95%. These are centers while they’re compliant with the patient’s diet, they ask the questions whether they compliant, they do the test correctly, they calibrate the machines correctly.  So in that scenario, obviously the quality of the test goes up and the specificity becomes about 95%.  But there’s no question that there is a group of healthy controls or healthy “people with no GI symptoms” and that their breath test is positive. Now the question becomes is that well is this a false positive or a true patients with SIBO that is just asymptomatic? Because remember, asymptomatic dysbiosis does exist. A lot of people with with dysbiosis are walking around with virtually no symptoms at all and asymptomatic bacteria can happen all the time, especially during pregnancy. So it’s not an uncommon thing. So this can happen. And one study that essentially proved that is the study by Joseph Allegretti that what did they did is that they looked at people who received a fecal transplantation for a C diff infection. So for people who C diff was eradicated but they develop IBS like symptoms, if the donor was breath as positive, the chance of getting those symptoms was 50% as opposed to if donor was breath as negative, which was 14%.

So that means that even though those individuals had no symptoms, their breath test was positive. So there is something wrong with their microbiome. So giving that microbiome to patients with C diff infection caused IBS, which is a fascinating concept. So if you want to do breath in your office or see whether the indications preparation and interpretation of breath is, you can use North American consensus as a guide for yourself that now it’s been five years since we published at.

So this is how a normal breath test looks like. So the patients fast overnight, they come in and we measure hydrogen methane adjusted based on CO2, every 30 minutes, every 50 minutes we measure it. And usually what we see is that if you do it for 180 minutes, you see a rise at the end. Sometimes you see a rise a little bit earlier. But what is positive is if you have more than 20 part per million of rise from baseline within 90 minutes, that means that there is excessive amount of bacteria in the small dial that is fermenting and repeating that up.  So just to give you, it’s interesting that that cutoff kind of correlates with deep sequencing data as well. So this is a small bowel aspiration data based on deep sequencing and very commonly proteus bacteria are very abundant and patients with SIBO that correlates with it. And firmicutes are actually low. So which is interesting. So in this patients we’re seeing and even correlated with energy metabolism of hydrogen production, pathways of bacteria. So seems like the 90 minute is almost the perfect cutoff for lactulose at breath testing.

For the glucose breath testing also we proposed a 90 minute cutoff.  Having said that because glucose gets absorbed within the first two or three feet of the small bowel, you probably can just look at the whole 120 minutes of data. One important thing about glucose is that, well there’s now debate and then probably we are going to change things in the next North American consensus that the cutoff probably for glucose should be lower because it doesn’t cover the whole small bowel. And instead of 20, the data, especially the data that recently [inaudible 00:26:01] proposed is that probably the best cutoff is 12.

So for methane though it’s the cutoff is well established. The cutoff is 10 part per million. And this is, as I said, it can be the small bowel or the column. So you don’t look at the rise, you look at an absolute number and this 10 port per million, it’s interesting that it also, it works both for glucose and lactose. And this is a paper we just published I think about six months ago, that it works both for glucose and lactose and also correlates with constipation gas and less diarrhea. More importantly, it correlates with the load of methanobrevibacter smithii, which is the main archaea in our body that produces methane and also positivity remains stable on repeated measurements if you don’t treat the patient. So that’s very important. Because one argument is that well is method is just a sign of a slow transit.

Well I mean the answer is not, is no because sometimes we give antibiotics to somebody with IMO and [inaudible 00:27:26] and methane drops and patient has less symptoms. So it’s not just a matter of trans. And another very cool thing that we showed is that if you treat the patient for 14 days and you measure methane every day, a fast methane and it’s actually very nicely you see a drop in the methane levels of with antibiotic therapy. This is very important because for example, if I see a patient that now after seven days responded to therapy, then next time that I treat patient I will do it for seven days. I won’t do a 14 day course. On the other side, if I see that okay on the day 14 a methane is still elevated, that means that I’m using the wrong antibiotic. So I will use a different antibiotic to or whatever modality you want to use the plant-based antibiotics or you want to do elemental diet. But regardless, whatever you did, you need to switch gears.

So how do you manage bacterial overgrowth? Essentially we think of it as three pillars. Number one is that, is there a modifiable underlying cause that you can get rid of in, for example, is there narcotics onboard and can you get rid of it or can you give antagonist to narcotics? Can you decrease the amount of inflammation in the small mouth? But unfortunately not many times you’ll find a modifiable cause of SIBO. So you need to do induction of remission, which you can do antibiotic or elemental diet or you can do maintenance of remission. That essentially includes diet MMC, sort of modulating drugs that people talk about and also counseling the patient regarding recurrence.

So it’s important to understand that if antibiotics have an efficacy of about 50%. So that’s very important to understand because just because one patient does not respond to antibiotic therapy, that doesn’t mean that patient doesn’t have SIBO. Most of the studies looked into hydrogen SIBO and the antibiotic study data on I’m not going into the plant based antibiotics because that’s not the area of my expertise. You guys know more than me about that. But the antibiotics that we have by prescription [inaudible 00:30:06] and flail has been tested and showed positive response. Data for Rifaximin is actually interesting because we know that refaximin is approved for IBS diarrhea. But the only determinant of response that we could find that determines the degree of response in IBS patients to refaximin is positivity of breath test. If breath was negative, the response was 26%, which is less than possible and if it was positive was 56%, if the response was that the breath became normal at the end of the treatment response rate was 76%.

So it’s determines a response in IBS patients. So how about [inaudible 00:31:13] are refractory to a lot of antibiotics. So what we need to do is to suppress the hydrogen produce a bacteria. So they can’t produce methane and also suppress the archaea. So usually we do that for example [inaudible 00:31:35] augmenting we anecdotally use. So that’s a achievement that we try. So Ben talked about the data on elemental diet. There aren’t many sort of formal studies, but documental data study 2004 that show that using yvan X at the trial of 93 SIBO patients, they had 66% symptom improvement after two to two or three weeks of elemental diet. And by elemental diet, I mean exclusive elemental diet, I mean they’re not allowed to take anything else other than water. They’re allowed to have black coffee. So at the response rate is actually for improvement and normalization of a breath.

This was actually 80%, which is even better [inaudible 00:32:39]. Also we know that elemental that it can works on Crohn’s disease, a CDI can even within [inaudible 00:32:49] gastroenteritis. So if you have a patient that has overlap of those, an intriguing option. Another thing’s that you should always tell your patients about chance of recurrence of disease to these patients because so they understand. So they’re not disappointed when the symptoms come back. I almost tell them you have about 50% chance of recurrence at one year. So they understand that it’s not like a UTI that you just treat and it’s gone. This is different.

So diet at Cedars, we use a low fermentation eating planning, which includes meal spacing plus a list of food that are not as a restrictive as other diets because of extremely restrictive diet eventually can lead to micronutrient and micronutrient deficiencies. So I use this as a maintenance of remission mortality. So what else do we use? We use migrated motor complex and modulating a drugs, for example, and [inaudible 00:34:08] at low dose and also low dose [inaudible 00:34:16]. There are other modalities, obviously you can do those. [inaudible 00:34:19] has been used, [inaudible 00:34:19] has been used, but unfortunately the number of promotility drugs out there are not a lot of them.

So this is essentially how the algorithm that I’ve followed generally for bacterial lower growth. So if I have hydrogen sulfide or hydrogen predominant of bacterial overgrowth, I treat them bit [inaudible 00:34:46] I mean also works on them. And also if you have excessive random methane, then I usually use [inaudible 00:34:55] for 14 days. And then I educate the patient about risk of recurrence and adopt this strategy for maintenance immersion, whether it’s diet or it’s a migrating motor complex modulating drug. And if symptom occurs, obviously I repeat this. In the meanwhile though every time I do this I always look at the underlying causes and whether there is something that I can change.

So these are the take home messages. So essentially it has myriad of symptoms, we can diagnose bacterial overgrowth and also EMO with breath testing and also a breath testing I showed you some data that helps tailoring antibiotic therapy and predicts response to refaximin and [inaudible 00:35:49] diarrhea patients. And then don’t forget the three pillars and revisiting them constantly when you’re managing these patients. And this is our team. And at this point I’m happy to answer any questions.

Dr. Weitz:            Let’s see, let me ask the first question here. Dr. Rezaie, I know with your elemental diet, I was looking at the description of it in the book and it’s somewhat similar to a low FODMAP diet. Now the low FODMAP diet has a certain amount of data to substantiate it. Why not go with a low FODMAP diet rather than the elemental diet?

Dr. Rezaie:          Well, I mean this would be a good question for a dietician. They’re not necessarily similar. The low fermentation is way more liberal, low FODMAP is way more strict. So that would be, so that’s essentially the difference. So the thing is that yes, you are right, low FODMAP diet is there’s a lot of data behind it. And because of that we know that it’s not healthy in the long run and you have to reintroduce food within one month, which doesn’t work in SIBO patients. Well, I mean you reintroduce things in one month while symptoms are back. So that’s the issue.

Dr. Weitz:            Now I know you’re not a big fan of probiotics. Maybe you could tell us why.

Dr. Rezaie:          Well, I mean the bottom line is that SIBO is not a primary disease. So as we discuss the main causes this motility and also a lot of other causes that leads to accumulation of bacteria. So pouring more bacteria in the small bowel is not going to fix that problem. And that’s the issue. In fact, actually patients with bacterial over growth can get worse with probiotics. I mean there is a very interesting study that can department did at temple that they give [inaudible 00:38:06] to healthy controls by the end of one month. The patients with [inaudible 00:38:17] started to have more bloating distension. But more interestingly, they started to have more methane, which is fascinating. So we started to give them EMO, which is fascinating because [inaudible 00:38:30] is a hydrogen producing bacteria.

Dr. Rezaie:          And on top of it, the data with fecal transplantation with IBS is nothing short of disappointment at this point. And there are a couple of studies that are not just negative, they’re showing that actually placebo is superior to [inaudible 00:38:50] meaning that patients are getting worse. So this, and if you think about it, fecal transplantation is the ultimate probiotics and we know it works in certain situations. There’s no question that they work in the senago C diff infection of the recurrence of it. But in this scenario yet to see any robust data that it helps and if anything, we have data that it may be even making it worse.

Dr. Weitz:            Now you mapped out the microbiome of the small intestines. So obviously there’s benefits to having a certain amount of bacteria there. And one of the rationale for probiotics is we often use the analogy of a parking lot and there’s only so many parking spaces, and if you can park some good cars there, you can keep the bad cars from taking up those spaces. So if you are using antimicrobials or antibiotics and you’re killing some of the bad bacteria, you might be leaving open parking spaces. And so that would be the rationale for potentially for using probiotics.

Dr. Rezaie:          I mean possibly that’s but clinical data is you is yet to pan out with that.

Dr. Weitz:            Right. Somebody asked if you could give that reference for the fact that colonic bacteria, it takes 40 minutes to produce hydrogen at a level that can be detected in a breath.

Dr. Rezaie:          Sure. This study is done by Read, that’s the first author. It’s in got and is published I think in 1985. So if you look at that study, they is actually infused [inaudible 00:40:58] and that led to rise in the hydrogen and it took about 40 minutes for the rise to reach a level of two department.

Dr. Weitz:            Let’s see, as somebody mentioned that there’s several studies that have shown, in fact, I’m pretty sure there’s at least one meta analysis showing that probiotics can be beneficial. And it’s been hypothesized that probiotics actually have an antimicrobial effect.  Let’s see, is SIBO really bacteria overgrowing from the large intestine or is bacteria coming down from above?

Dr. Rezaie:          No, it’s bacteria from the colon.  So these are the disruptors that we see in the small vowel overgrowth that we see. And as we get closer to the colon and SIBO patient is more similar to the colon and healthy controls is not.  So it’s coming from the colon.

Dr. Weitz:            Is the importance of a healthy ileocecal valve important?

Dr. Rezaie:          Yeah, IC valve is important.  And not surprisingly, not the patients with, IC valve resection, they will have higher chances of bacterial lower growth, but not all of them.  But it shows that if you have healthy migrating motor complexes, you’ll probably do well.

Dr. Weitz:            Given the fact that there are some patients who as a result of Crohn’s or some similar disease have had to have their colon removed, they no longer have a normal colonic microbiome and we know how important a microbiome is for health.  In that situation, is it preferable for the small intestine to have a higher amount of bacteria?

Dr. Rezaie:          Ask the question again.

Dr. Weitz:            Is there ever a scenario in which you might want the small intestine to have more bacteria?  In the example, in the case of a patient who no longer has a colon because it was surgically removed, they no longer have a colonic microbiome.  We know how important a microbiome is.  In a situation like that, is it beneficial for the person’s health to have higher bacteria?  In other words, should their small intestine become their new microbiome?

Dr. Rezaie:          No.  So the way colonic mucosa interacts with the bacteria and the small bowel or is completely different.  So you can’t really use small bowel as colon.  So I can’t think of a scenario.

Dr. Weitz:            Okay. Great. Well we really appreciate you showing up despite being sick with COVID and hopefully you’re going to recover quickly.  If anybody doesn’t have any other questions?  Then thank you very much Dr. Rezaie. 

Dr. Rezaie:          No, you’re welcome. All right.

Dr. Weitz:           And thank you everybody for joining and we’ll see you next month.

Dr. Weitz:            Thank you everybody for joining and we’ll see you next month. Thank you for making it all the way through this episode of the Rational Wellness Podcast. And if you enjoyed this podcast, please go to Apple Podcast and give us a five star ratings and review. That way more people will be able to find this Rational Wellness podcast when they’re searching for health podcasts. And I wanted to let everybody know that I do now have a few openings for new nutritional consultations for patients at my Santa Monica White Sports Chiropractic in Nutrition Clinic. So if you’re interested, please call my office (310) 395-3111 and sign up for one of the few remaining slots for a comprehensive nutritional consultation with Dr. Ben Weitz. Thank you and see you next week.