New Insights Into the Causes of SIBO from Jejunum Research, with Clinician and Researcher Dr. Richard McCallum
One theory of small intestinal bacterial overgrowth (SIBO) is that it’s caused by bacteria in the colon moving up. A new study on one section of the small intestine, the jejunum, challenges that concept. The study—which used a new technique called polymerized chain reaction (PCR) to look at bacterial genomes—found that the jejunum has its own unique microbiota. Positive breath tests also did not correlate with bacterial overgrowth in the jejunum, but rather jejunal dysfunction. Dr. Richard McCallum, gastroenterologist and researcher on the study explains more about these findings and what they might mean for SIBO treatment. We also discuss how proton pump inhibitors (PPIs), breath tests, diet, prokinetics, and hypochlorhydria fit into this picture. Join us for a very insightful conversation!
Dr. Michael Ruscio, DC: Hi, everyone. Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. Today I’m here with Dr. Richard McCallum, and we are going to be talking about a presentation I heard some great things about from the recent SIBOCON conference, entitled “The Microbiota and the Jejunum: Relationship to Bacterial Overgrowth and Breath Tests.” So, Richard, thank you for coming on the show today.
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Dr. R’s Fast Facts Summary
- In general, the research and clinical thinking behind SIBO is moving away from the thought that the problems originate only in the lower colon and travel upwards.
- The more likely case is that the upper colon has its own set of issues.
Glucose vs Lactulose Testing
- McCallum prefers glucose testing
- It seems that more data supports the glucose test being superior to the lactulose test
AI Motility and SIBO
- McCallum reinforces that motility often improves all on its own as your symptoms improve
- See clinicians notes highlighted in the transcript
- Get help with SIBO.
- Get your personalized plan for optimizing your gut health with my new book.
- Healthcare providers looking to sharpen their clinical skills, check out the Future of Functional Medicine Review Clinical Newsletter.
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Dr. Richard McCallum, MD: Glad to be on the show. Thank you for inviting me.
DrMR: Absolutely. Can you tell people just briefly about your background before we jump in on everything else?
DrRM: Yes. I’m a gastroenterologist. Grew up in Brisbane, Australia, and came over with the thought that I might evolve my knowledge base and go back and re-contribute to the Australian developments, but I got lured away into academic medicine over here. And I’ve evolved up the ladder into directing divisions of gastroenterology, training programs, fellowships, departments of medicine. I’ve been a dean. I’ve run the gamut. And now I’m happily back into gastroenterology research, NIH-funded research, trying to continue to work.
I’m a motility specialist if you look up my title. In some ways, I’m looked upon as looking at nerves and muscles, and how the brain and the gut connect up. Gastroparesis and gastric emptying is a big part of my publication record. But recently, we’re evolving into the mysteries of the microbiota and how that may, in turn, tell us about nerves and muscles, and how the gut may have dysfunction, including how the stomach may not empty well if there are abnormal bacteria in the small bowel. So we’re being a little more inquisitive and a bit more open to looking at new directions.
Looking at the Jejunum for SIBO Causes
DrMR: Great. And I heard some really great things about the lecture that you gave at the SIBOCON. I believe some of that was challenging—I guess I would call it—the SIBO community’s consensus regarding SIBO. And I should just say, there’s this niche in the States of very SIBO-centric providers. I do think some of their conclusions are a bit premature. So I really welcome discussing different viewpoints, challenging some viewpoints, because I think that’s how we really find what facets of our arguments are tenable, and what really isn’t supported or might be misreads and need to be revised. So I just want to make sure this starts off with embracing any challenging of the typical SIBO thinking.
And would you tell people a little bit about that presentation? Maybe a few of the points you felt were a bit more relevant or salient?
DrRM: Yes, thank you for that invitation. Well, we do—diagnostically in this country and I think most parts of the world—a test called a breath test where you drink a sugar solution. It could be glucose. Some people use lactulose, which is a non-absorbed sugar. And the assumption is that bacteria lurking in the small bowel and colon attack this bacteria, attack this glucose, and make a lot of gas, particularly hydrogen and some methane.
I questioned a little bit about where we are focusing on this overgrowth of bacteria. If we use glucose, which I only use, we assume that the majority of glucose is absorbed and is in contact with the jejunum and that only a small fraction is not absorbed and trickles down into the colon. And therefore, in the first one hour after you drink a glass of glucose, in patients who have what’s called a positive test for SIBO, the hydrogen or methane goes high, becomes elevated, and we call that a positive test.
So we went back and cultured, put an endoscope into the small bowel—jejunum specifically—and took aspirations of fluid from the small bowel. We did both anaerobic and aerobic culturing, and we looked at PCR, a new technique (polymerized chain reaction), in order to look at the particular bacterial genomes, at the individual DNA. And we tried to understand, is there a connection between the positive breath test, as sort of baseline hydrogen/methane elevation, and real data? Can we find these bugs? Are they culturable or are they present on PCR? And our conclusion was that the jejunum contains a distinctive bacteria population of facultative anaerobes and oxygen-tolerant obligate anaerobes, similar to those found in the oral cavity, actually. We also sampled saliva in those patients.
And what we found is that there really wasn’t much similarity between the organisms and PCR data in the jejunum compared to the colon. And where there’s been a teaching in the past that somehow retrograde flow from the colon goes up into the jejunum—and that in turn leads to this positive gas production as food comes down, and sugar, in particular, is broken down—we found that indeed we could not correlate a positive breath test to the overgrowth of bacteria in the jejunum. However, a positive breath test did indicate an altered jejunal function in what’s called microbial dysbiosis. Bacteria could have been non-active, may have died, but there are DNA-positive findings still which may have disturbed or caused the symptoms of what we call SIBO (bloating, gas, belching, burping, altered bowel function).
So we evolved a bit to the fact that the jejunum has its own unique, intrinsic microbiota, which could explain why many patients present with gas, bloating, abdominal discomfort, and altered bowel pattern. And you wouldn’t have to invoke the fact that it’s all colonic flora that’s come up into the proximal gut and is now attacking or liberating gas at all. We didn’t find many similarities between the jejunal PCR data and the colonic PCR data. We found a lot more similarity with saliva if anything. That the upper gut was somehow more related to the jejunum than the colon.
So we’re questioning, I guess, where a positive breath test emanates from. We believe it doesn’t require much colonic help or contamination, that some change in the upper flora of the gut could explain symptoms.
And you might ask, “Well, why would the upper flora change?” We think one major problem that’s going on now is the use of proton pump inhibitors. 20% of the country is taking a proton pump inhibitor to block acid because of acid burning, heartburn, reflux, indigestion, tummy pain. It’s used very, very extensively. And when you take acid away from the upper gut, the way we were born… acid is supposed to cause a hostile environment and tries to limit bacterial presence in the upper gut, tends to keep it down. But when you take acid away, as PPIs do, then you may liberate bacteria that have been somewhat suppressed and encourage them to colonize further and grow.
So I think we’re looking at the upper gut as being a unique sort of idiopathic component. It has its own unique flora, microbiota, which may be very different from the colon, and may have its own set of symptoms and its own set of pathologic diagnoses.
DrMR: Fascinating. So there’s a ton there to dig into. And I really, really find this quite, quite interesting. Let me just clarify a couple of things for our audience, and if I misrepresent any of these in my summary, please feel free to let me know.
Just quickly for the audience: we have these three sections of the small intestine: the duodenum, the jejunum, and the ileum.
DrRM: That’s correct.
DrMR: So they were sampling from the middle section of the small intestine.
DrRM: Yeah, If you figure the small bowel’s about 20 feet long, as quoted, the jejunum may be 10 feet to 12 feet, probably 12 feet long. We were sampling about 12 inches below where the jejunum begins, which is about two feet from the stomach.
DrMR: So they’re performing this sampling. And just to provide context for those of us in the audience who aren’t clinicians and don’t have the requisite detail coming into this conversation, there are a couple of theories in terms of where SIBO comes from. And Richard, feel free to add anything to this. But as I’ve come to understand it, there are maybe three main theories.
One is that the bacteria from the colon are able to kind of reflux upward into the small intestine. Two is that oral bacteria don’t get killed in the stomach (or stomach bacteria also), and they flood down into the small intestine. And then the third could be that the immune function in the small intestine is inadequate, allowing dysbiosis. Those might be the three main forerunners. Richard, would you modify or add anything to that?
DrRM: No, I think that’s a good summary.
DrMR: Okay, and so what Richard’s research is essentially finding is that the mechanism of what’s causing SIBO—or at least what’s suggested based upon his sample—is more bacteria from the top trickling down, rather than from the bottom refluxing upward. Which is very interesting and may tell us that looking more at (like you mentioned) things like acid function in the stomach and use of acid-lowering medications may be an important aspect. And we do know there is research connecting and showing there’s a higher prevalence of SIBO in those who use PPIs, so there are certainly other data that support this contention.
DrRM: Yeah, the problem is there are a couple of different camps. If you’re a purist and say, “I’m going to see patients who come to me with, ‘Doctor, I’ve got the most gas in El Paso. I’ve got bloating, I’ve got distension, I’m unhappy. I’ve got gas and bloating. Can you evaluate me?’” then we’re doing the breath test. And the breath test is, by nature, swallowing a glucose liquid which gets primarily absorbed in the upper gut and some trickles down to the colon. But you’re putting most of your money, as it were, in the proximal six feet or so—10 feet—of the gut. Within an hour, the glucose has touched something and there’s a positive response with gas.
The other group is the Irritable Bowel group. It’s another world. Irritable Bowel has all its own criteria and its own rules and regulations. But there is an attempt to merge the findings a bit of the gas and bloating, which invariably accompany Irritable Bowel. Can that be also a form of SIBO? And therefore, SIBO begins to become synaptically linked to Irritable Bowel Syndrome. You can do that, but you’ve got to be careful you don’t drag along the breath test with it. The breath test is not a test for Irritable Bowel.
“Patients and clinicians need to remain objective about SIBO. Listen here to find out why we may be wrong in how we think about the cause of SIBO. And which test stands out as potentially more accurate?”
DrMR: Yeah, agreed.
DrRM: The breath test is—theoretically, in my mind—a test for abnormal bacterial flora overgrowth in the upper half of the gut. I think Irritable Bowel as it was born, and even today as looked upon by most clinicians, is a problem of the lower half of the gut, specifically the colon. And gas and bloating now is being bounced around between those camps. We’d like to incorporate Irritable Bowel and therefore, we can say we’ve got to kill these bacteria, maybe small bowel or colonic. Whereas the puristic SIBO people, I don’t think we need to invoke the colon, quite frankly. I think we’ve got enough action in the upper half of the gut. So that’s what can be a little confusing to the audience when they may read something.
Positive Breath Test Correlates with Dysbiosis
DrMR: And again, there’s such a rich tapestry here of topics to potentially dig into. I do want to cue in on one thing you said a moment ago, which I feel is worth repeating, which is that a positive SIBO breath test did correlate with dysbiosis or imbalance.
DrRM: Yes, it did.
DrMR: So can you expand upon that a little bit more? And try to delineate between what we’re thinking of previously as this colonic bacteria that refluxes upward and you have this overgrowth from the colon, as compared to, it may not be quite that specific, but there may be just this general imbalance in the small intestine. Or this dysbiosis.
DrRM: Yeah, so a positive breath test, in our case, was associated with very low viability of the jejunum microbiota. However, microbial dysbiosis in the gut has been associated with a variety of diseases where the causal connection’s not always clear. One interesting example is, say, hepatic encephalopathy, where antibiotic treatment of so-called dysbiotic intestinal microbes with rifaximin now has proven to be very effective in helping patients who are encephalopathic. So we’re wondering whether you need viability or whether you have the sequelae of those bacteria that are still present in the small bowel. May not be culturable or may not be present more than 10 to the fourth or fifth, whatever the upper limit is, and may not be on a PCR. There may still be dysfunction that’s been induced by their presence and by their metabolic effects.
DrMR: Yeah, and I’m in agreement with that, where I think we sometimes are looking for very detailed lab analysis to tell us exactly why a person is suffering from a given symptom or ailment. And sometimes we have to zoom out and just look at, well, if we know something like rifaximin seems to work, perhaps this is treating this imbalance even if we’re not quite sure where it comes from. I think that’s still being sorted out, and we don’t know all the particulars, so what we can look to more closely is, what kind of outcome data do we have? What kind of treatment data do we have? And then we make more of our clinical decisions around the treatment data rather than speculating from the type of bacteria or the mechanism. And there’s a time and a place for both, in my view, but because some of these particulars are still being sorted out, it makes me revert more to relying on the clinical outcome data.
Would you agree with that? Would you modify that at all?
DrRM: Well, what we could say there is that these bacteria are dormant. It’s well-known that certain pathologic bacteria can enter a quiescent state where they remain intact and alive. They actually do not form colonies as in standard cultures so that the variation we found and the viability of these bacteria could be related to differences in the luminal and mucosal environment. And the capacity for a nutrient absorption which leads to the positive breath test may be changed by the immune responses, bile salts, inflammation. So there are variables that could have explained our data, but I think what we set out to do initially was help address the concern among clinicians. Hydrogen breath tests are all we have in a way or the breath test. Because no one wants to put a scope down every patient and culture their small bowel. That’s a lot of work and very expensive, and you lose a day of work. So that’s not going to happen. This test is a simplistic three-hour test. You swallow a glass of glucose, measure your breath, and go back to work. But is it the be-all and end-all of testing?
And what we found is that, no, it’s not. We know it’s not. We have to accept the fact that it’s somewhat unpredictable and we couldn’t correlate a positive breath test with either the anaerobic or aerobic culture, or with the PCR. But there was a definite positive correlation, actually, between a low viability of jejunal bacteria. There’s no similar correlation of glucose with either the number of bacterial colonies or the DNA-based bacterial counts. Instead, we found higher signals in the hydrogen and methane breath test with lower viability of jejunal bacteria, and this brings up this dysbiosis question. So I don’t think we changed clinical practice. I’m sure, just like in my place, we’re still doing breath tests every day, madly, and we’re still reading it.
But we still must wonder what the future is, which would be, we’re going to have to do better than rely on glucose being attacked by a bacteria and producing hydrogen and methane. We’re going to have to do some kind of sampling from the proximal gut, maybe in the duodenum, which is much more clinically relevant or reachable in clinical practice. We all do upper GI endoscopies. That’s a simple, everyday procedure. This could be adapted to a brush that could rub the mucosa, and aspirate and sample the bacteria that line or are clinging to the mucosa. We do need some practical way of finding out what our bacterial count is.
The point with the study I’m doing right now is actually just that study. We’re doing brushings of the duodenum and the stomach and the esophagus, along with saliva samples, to try to reinvestigate the upper gut microbiota. What is the line-up in that upper gut microbiota? We’ve focused a lot on the colon and stool samples. Let’s return to the upper gut a bit, which is where the food initially is entering, and learn more about it, make it more practical for the clinician. Maybe he could sample the upper gut every day during endoscopy and not have to worry about doing breath tests and other things that not all places have.
Lecture: Microbiota and the Jejunum: Relationship to Bacterial Overgrowth and Breath Tests
- Dr. McCallum attempted to culture bugs that are suggested from SIBO breath testing. He found
- Jejunum (middle of the small intestine) similar to oral bacteria and Jejunum bacteria were not similar to colon bacteria. This counters the philosophy that SIBO is caused from colon bacteria flowing upward into the small intestine.
- Could mean low stomach acid causes SIBO
- SIBO breath positives were correlated with dysbiosis in the small intestine
- Dr. R’s notes
- Local immune response might be important in causing small intestinal dysbiosis
- Low FODMAP might improve the immune system thus improve dysbiosis, presumably, as low FODMAP diets reduce inflammation.
- These findings might also indicate that where the bacteria are coming from is less important
Glucose vs lactulose testing
- Dr. McCallum prefers glucose testing
- Positive distal SIBO (end of the small intestine) may not be relevant as bacteria naturally increase toward the end of the small intestine
AI motility and SIBO
- Dr. McCallum reinforces something I have been saying for a while: motility often improves all on its own as your symptoms improve
- What about the fact that IBS correlates with IBS Smart (the test for motility autoimmunity) results? This may not be relevant in the long term
- Serum gastrin if you’re not on a PPI – over 70-75 could mean you need HCl
- Gastrin is not perfect, so be cautious
- Ask your gastroenterologist to assess the following at endoscopy: biopsy findings for atrophic gastritis and Small Bowel Intestinal Metaplasia
- American Motility Society Does glucose‐based hydrogen and methane breath test detect bacterial overgrowth in the jejunum?
- BMC Microbiology Journal The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon
Low FODMAP Diet and SIBO
DrMR: And you bring up a good topic, which is food and how food impacts this whole picture. And one of the hypotheses that I’m currently ruminating on is—and you alluded to this—there could be this, for lack of a more specific term, immune system imbalance in the small intestine. Perhaps there’s some inflammation and this inflammation is creating a milieu that’s allowing dysbiosis to thrive.
DrMR: When we look at some of the research showing that a low FODMAP diet can lower inflammatory cytokines, it’s interesting to ponder if the low FODMAP diet is helping not because it’s starving SIBO, per se, but because it seems to have this beneficial immunomodulatory impact. And perhaps this is part of the reason why we’re seeing the symptomatic improvements that we’re seeing in a low FODMAP diet. What do you think about it?
DrRM: The low FODMAP certainly covers a huge waterfront, from low gluten to low fructose to low everything, but I think it does address more the upper gut than probably the colon.
Certainly fructose is given an asterisk. We think of malabsorbed fructose as a component of food that ends up, probably, in the colon. And when I do a fructose breath test, I’m looking for a late rise in hydrogen or methane because it’s gone down into the colon, which takes about one and a half to two hours. And we’re seeing a late rise.
But I think for the other things in low FODMAP, we are really addressing the upper gut, and I think your points are well-taken. This unleashing of the dysbiotic environment somehow needs closer evaluation. Maybe sampling before and after FODMAP diets, or doing more investigative work than just saying, “Take a low FODMAP diet, good luck,” which is what tends to happen now. We don’t have a lot of hard data about what has changed in the gut on a low FODMAP diet.
DrMR: We certainly need more, I think, about what changes are occurring in the small intestine. But again, because of the difficulty with assessing the small intestine, there’s been a real damper on that. I think it could be very exciting to see what happens with these smart capsules. I don’t know how cheap they’ll be, but at least they could be a non-invasive way of getting a better idea of what’s going on in the small intestine.
DrRM: Yeah, that’s why I’m working a bit in the duodenum. In a way, it’s a “poor man’s” jejunal sample! But given life and due to the fact there are millions of endoscopies done every day—and we’re biopsying small bowel for sprue and we’re biopsying stomachs for H. pylori—let’s just brush the duodenum and see where the duodenal microbiota profile fits into the big picture. Are you high-normal? Are you very, very low? Could we begin to incorporate that into a clinical profile, and try to incorporate that into a symptom assessment?
It may be a dead-end, but we’re looking at that because it’s here and now. I do think capsule sampling could happen. GPS signaling to open the capsule, like a little trap door opens and fluid enters. But then you’ve got to work out a way to recover it. Do I have to strain my stool? Do I put my capsule on a fishing line and yank it back?
DrMR: Yeah, it’s not easy.
DrRM: There are still some unknowns. Whereas with the endoscopy people, sooner or later—gas and bloating, this and that—you end up getting an endoscopy anyway. And that could be a good time to actually brush the duodenum and see if we could extrapolate. It’s not the jejunum but it’s pretty close. The jejunum might be greater than 10 to the fourth bacteria, to be SIBO. Duodenum might be greater than 10 to the third. I mean, they’re not that far apart, and there’s no bowel there to block it. So you would think that jejunal mischief could easily regurgitate into distal duodenal mischief and it could be reflected in a sample. I guess I’m a clinician at heart, and I want to help patients. I also want to do research, but I don’t want to become too airy-fairy and ivory tower. We do want to do something that might change things tomorrow.
DrMR: I deeply appreciate that. I think that’s something that we need more of.
Glucose versus Lactulose SIBO Testing
I want to transition to breath testing. There’s definitely controversy regarding glucose versus lactulose. I try to remain pretty objective and non-invested in one test compared to another. But there are a few nuances I think would be interesting to discuss. In the published literature—if you were to read just that—I think it’s easier to conclude that glucose is the better test mainly because of the false positives reported with the lactulose test. And just for our audience, a false positive means the test says you have a condition when, in fact, you don’t have a condition. And this is something we know occurs with the lactulose testing.
Now, the counter-argument made against that is, the glucose doesn’t get all the way to the end of the small intestine and therefore, you may have a false negative. And I think we can make a case for that. I don’t think it’s a very strong case. When you look at the data trying to correlate IBS symptoms to either a glucose test or a lactulose test, there does seem to be a tighter agreement between the glucose test and IBS symptoms than there does a lactulose test. But—and this is a key point I’m curious to get your thoughts on—as best as I’ve been able to read it, it does seem that most of the data finding the higher false positives in the lactulose testing had a cut-off window that was too long. Went up to 120 minutes in some studies, even 140 minutes. And there’s a more contemporary view that if we cut off the read at 90 to 100 minutes, we will decrease and guard against the false positives from the lactulose test. And that’s more speculation, I don’t believe that’s been fully sorted out, but I think it makes sense. What are your thoughts there?
DrRM: Well, I think for the audience, what we’re saying is that when lactulose is swallowed, somewhere between 90 and 120 minutes, it’s going to reach the colon as a non-absorbed sugar. And these colonic florae, billions of them, are attacking this very happily and joyfully and making a boatload of gas. Just like if you’re milk-intolerant and don’t have lactase, your milk goes into your colon and you make a lot of gas, and maybe even have diarrhea.
So what we don’t know… My transit time from the mouth to the colon could be 75 minutes, yours could be 95, your wife’s could be 105. That variable is continuously hovering over my head at night when I’m asked to interpret a lactulose breath test. So the theory is that if I just gave you lactulose, then you would go up around 100 minutes. Now, if you’ve got bacteria in the distal small bowel, you have a peak around 75 to 85 minutes, and then if we hold our breath, it becomes a little bit of a plateau. And then boom, up it goes again at 100, 110 minutes when it hits the real deal, the colon. And we get two peaks (what’s called the double peak), and that’s how you’re taught to interpret the lactulose breath test. We all were taught that.
But meanwhile, back on the farm here at night, when I’m interpreting today’s breath test, and I’m trying to be fair and moderate. Is this a first peak? Is this a peak that never really goes away and it’s one big peak? Is that where it hits the colon? Can I separate a first peak being the distal ileum from the second peak, which is the real colon? And over time, I found that I really could not do that and I did not want to do it. It became too much of a nighttime guessing game. I really didn’t feel comfortable. Glucose obviously takes away that doubt, and you get 90 minutes to make a decision.
Now, people have actually done some sophisticated studies and labeled glucose with isotope. And people have found that if you give a 90-gram bolus of glucose, some unabsorbed glucose can enter the colon and can fuel the production of hydrogen and methane. In fact, even Levitt, one of the early pioneers from Minneapolis, showed that there was evidence of incomplete absorption and there was colonic hydrogen production that can occur and can be attributed to a component of glucose. Even though we think glucose is absorbed in the small bowel, and in the small bowel, mainly the jejunum.
But I think compared to lactulose, where none of it’s absorbed, you’d have to say that you’re pushing the envelope to put all your eggs in the lactulose basket. You’re going to make a lot of false-positive calls and that can lead to a dangerous slope. Once you’re diagnosed, you’re sort of labeled, and then your career goes on. You get recurrent antibiotics, you get recurrent probiotics, you get this, you get that, all based on that original lactulose breath test five years ago.
I’m very conservative, in that I would like to be very clear that in the beginning, your glucose breath test was either positive or negative, and there was no mystery or doubt. It’s very clear. It can be read by anyone, someone in Missoula, Montana, Los Angeles, New York, or Australia. It’s very clear. Whereas the lactulose breath test is really very subjective and it could depend on your love of lactulose, your willingness or sort of general feeling that “I need to get some positive breath tests here.” You’re not limited or controlled by strict rules. And there are disciples and evangelists in this country who will continue to preach the gospel, I can’t stop them. But I think if you were coming into the business now, you’d have to be willing to say, “Let’s go with a guaranteed product, the glucose breath test, and I’ll work my way up from there.” But I’d rather be conservative at this point than go with lactulose.
DrMR: Yeah, I think that’s very reasonable. And as you’re describing that, I could also see there being two camps of people who may be able to better use each test. And this is certainly not an airtight case, it’s more just a thought, but you could make the remark that a conservative and skilled IBS or SIBO clinician might be able to appropriately interpret and navigate the false positives that a lactulose test may suffer from. If you’re newer to this or you’re not going to have the same nuance that goes into your analysis, then the glucose may be a better way to go.
But again, the data are better for glucose, so I think it is important that we state that. But again, it’s also controversial. The Rome consensus endorses glucose. The North American expert consensus sanctions or allows for lactulose.
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So as you’re saying, there is controversy. And I think the most important thing to take away, as you also touched on, is we want to be conservative. We don’t want to be looking for an excuse to overly use antibiotics or overtreat people. I think it’s always better to err on the side of caution and conservatism.
DrRM: Yeah, particularly after we found even the glucose breath tests didn’t have a strong correlation. For the North American consensus conference, I was on that panel, and to be quite honest, Dr. Pimentel, who is an evangelist, was very vocal and helped, I think, drive the final consensus document; that it was certainly not to be excluded, that is, the role of lactulose was to be given some credibility. The consensus on a numbers count was that glucose was the way to go, but given the fact that we had to recognize minority opinions on the committee, it was given a paragraph or two.
A Case for the Glucose Breath Test
But I think over time, the lactulose bandwagon has slowly become less and less, as more science and data have accumulated about how we can interpret the test, and the fact that the 10% or so that may be picked up is distal ileal bacterial overgrowth. You can’t really hold out that sort of goal, and for the other 90%, over-diagnose, under-diagnose or miss the real deal, which is in the first 10 to 15 feet of the small bowel. I think most people have come to sort of a comfort zone with that balance.
DrMR: Yep, and I think it’s very important that we remain objective. And that’s why, even though many of my colleagues run in, I guess what you’re terming, the more evangelical SIBO community, I’ve always been okay with saying, “Well, the data really do support glucose and we have to acknowledge that.” We have to, in my opinion, at least have a soft position on this test, and not be proclaiming ardently that lactulose is the best way to go. I do think you can make a case for either and that’s why I’m kind of a fence-sitter on this one. I could see an argument either way.
DrRM: Yeah, I’m a bit off the fence.
DrRM: I think the problem is, at our level of academic medicine… we go to conferences and we hear that a lot of well-meaning people, nutritionists, alternative medicine people, complementary medicine people, they use lactulose like the Bible. The patient walks in the waiting room and while you’re waiting to see the doctor, you do your lactulose breath test as sort of a warmup after you’ve filled out your profile data on the sheet. And it’s used almost like a Bible to separate the real deal from something else, and they often have extrapolated that from the literature.
And I’ve been surprised because when I’ve gone to meetings that are a little in that zone, of the complementary microbiota sort of meetings—where it’s not necessarily driven from the hardcore academic centers—there, lactulose has gotten a head start and has sort of been the Bible. I’ve had to preach fairly hard to tell people that unfortunately, it’s not the Bible, and you need to go back and read both testaments again. Because the current state of the art would be 70/30 against lactulose, maybe 90/10 in hardcore academic centers like Michigan, Mayo Clinic, myself and others.
So I think we’ve got to be careful. We’ve got to sort of hold the line, because people out there are over-extrapolating and then we’ve got half the country coming to me with SIBO as their diagnosis. Just like we had with the stool people, we end up finding candida and half my patients come to me on long-term fluconazole to treat candida in the stool, which is not a real deal. So we’ve got to be very careful. We have to, unfortunately, turn the floodgates back a bit and say, “Quite frankly, it’s gone way too far.” And we have to pull in the horses here. Current teaching is 90% glucose and I think we have to reinstate that.
DrMR: Well, I appreciate the pushback there and you do make what I feel to be an excellent point, which is, we have to be careful that practice guidelines are data-driven and not expert-driven. And as much as I appreciate some of the research that Pimentel has done and his increasing awareness of the bacterial component of IBS, it does seem that his influence has been very vast. And like anyone else, no one is perfect and there may be this warmness he feels toward lactulose that’s not totally correspondent with what the data show, but because his footprint is so large, it does lead to, as you’re saying, an imbalanced view in the community that lactulose is a clearly better choice.
So I think it’s an important torch that you’re carrying, which is trying to push us back to a more data-driven consensus on this.
DrRM: Good, good.
DrMR: And can we be in agreement on this: that when we get the data—because this is the thing I’m most curious to see—if we have another crop of lactulose studies that have a better cutoff time and we see the false positives be more in alignment with the glucose test, would that be what you would need to see to make you more comfortable with the lactulose test?
DrRM: The trouble is you almost have to do two tests, see. You have to really do a gut transit test, whether you gave them a drink of water and followed it down to the cecum, or whether… It’s not really practical.
DrMR: Sure. It may not be an adequate sample.
DrRM: You’d have to an objective test of your small bowel transit time when you walk in the front door, and we don’t have that data. We can’t get that data without giving you an upper GI barium swallow or a separate radionuclide study with a glass of water.
They’ve done the glucose test, where they gave radionuclide glucose at the same time as they measured breath, and they monitored the rise in breath hydrogen or methane and the status of the glucose. And that’s how they came up with the fact that 10% or more of glucose continues on into the colon, but the breath test has become positive before that happened. The breath test was positive when it was occupying the proximal and distal jejunum.
So the radionuclide stuff’s been done, the trouble is you can’t do a radionuclide lactulose test… well, you could if you were to label that lactulose with radionuclide. On the same day, they could go down to nuclear medicine, find out where it is, and make that statement. It hit the cecum in 120 minutes, but the glucose went up at 80 minutes. You could do that if you did a radionuclide label on the lactulose and nuclear medicine tried to predict where the isotope was, in the right lower quadrant down there in the cecum. You could do it. But that’s the only way you could really do it.
DrMR: Now, to those who would make the counterargument that you may miss some cases of SIBO when you’re using glucose testing, what is your response to that question?
DrRM: You know, a billion bacteria don’t stop at the ileocecal valve. There’s no airtight gate that’s locked every night by prison authorities. That’s not an airtight gate. All of us, in the last one or two feet of the cecum, of ileum have overlap. There’s a transition. I expect if you look at the counts, they go up to 10 to the 10th or more as you go into the distal foot or two of the ileum. So that’s a very, very, very gray zone of what the distal ileum is, the last foot or two or three, which is right near the ileocecal valve, where it’s not perfect. You don’t just go from a sterile small bowel and boom! You open the cecal gate and you’re in chaos with billions of bugs. No, no, no. That’s not real. There are bugs loitering and lingering and trying to sneak up into the ileum every day, and they’re in the distal ileum. That’s you and I. I’m not sure what the count would be, but it’d be at least 10 to the 10th or so in that distal couple of feet.
So I think that’s a bit overstating it. It’s one thing to say bile salts shouldn’t enter the colon. We all agree on that. That can cause colonic diarrhea. But I think there is a gray zone in the last two feet or so of the ileum where you’re going to have bugs wandering up from your colon trying to get a foothold. Now, the retrograde theory is, well, they go up three or four or five feet and get a foothold, and then that’s real SIBO, and so the lactulose gets that final four, five, or six feet. Whereas the jejunum, 10 to 12 feet is captured by mainly just the glucose.
I think you’re sort of trying to make a diagnosis of 10% of people or less who have this localized, segmental accumulation of bugs four or five or six feet from the cecum and that’s it. I think that’s a very unique subset of patients. It may be patients who are very constipated who push their flora up into the distal ileum. That could be a subset where the gate is pushed open by lots of right-sided stool that stretches the right colon, the ascending colon, and opens up the gate more. So in severely constipated people, maybe you could sell me that there are more bugs in the last four or five feet of my colon, where if I’ve got diverticula in the cecum, I would have more bugs.
But I think for the average story, I think the ability to go retrograde up 10 to 12 feet and end up in the jejunum… we have not clarified that story. How many colonic bugs end up 10 or 12 feet up and get into the jejunum? Our data would show very little, that jejunal flora by itself is not in any way colonic. And so there may be a SIBO of the upper gut, jejunum. There could be a subset of people where SIBO is in the distal two or three feet of your ileum, where there has been some loss of competence of the ileocecal valve. And perhaps it’s gotten up and you missed it with glucose. But I think that’s a very small minority, personally.
Avoiding False Positives in Breath Testing
DrMR: And you know, I think your argument makes sense. There’s certainly plausibility to the claim that the colonization intensity of the small intestine is not going to be the same at the first foot as the last foot, and we’re going to see this natural, gradual increase in the density of bacteria as we get closer to the large intestine. Which is one of the reasons why I’ve cautioned clinicians against looking at the end-of-the-line measure. Let’s say that that’s about 100 minutes. If you see someone who’s barely positive for a SIBO breath test, I do not look at that as a positive.
But I think it’s very important that the SIBO community stop doing that, because patients are always looking to rush to diagnosis because they want hope that there’s something to then treat. But it doesn’t mean as a clinician, you should jump upon that enthusiasm. Someone still could be a candidate for various treatments, but that would be more an empirical trial on therapy, rather than saying, “Well, your hydrogen was 26 at 100 minutes. You’ve got SIBO and now we need to use all these various treatments.” I would look at that as a non-positive SIBO case.
DrRM: Yeah, I think going past 90 minutes, you’d be pushing your luck. 90 minutes could be a conservative upper limit if you haven’t gone up more than 20 parts per million within 90 minutes. I think that would cover the vast majority of people’s transit time, although some people’s transit time can be as quick as 60 to 80 minutes. We’ve seen that. You could say less than 90 could be a start. But I wouldn’t want to open the gate, because I’ve tried to agonize over these myself, and you then get caught up with the first peak and the second peak.
This first peak is up to borderline positive… does it just continue that way all the way down and never really change, or is there a distinct peak? It goes up to 20 parts per million, it goes down a bit, and then goes up a second time. Under 90 minutes, I’d think it would be exceedingly rare, and possibly even 75 minutes might be the most conservative thing to do. That by 75 minutes, probably 75% of people have reached their cecum with lactulose, because lactulose is actually a luminal stimulant. By being a non-absorbed sugar, it actually increases motility on the way down. It’s not water. It actually activates motility as well. So you’ve got a lot of variables in lactulose. It’s a dirty kind of system in all ways.
DrMR: And something that I think it’s important to mention to bridle clinicians. There may be clinicians saying, “Well, I’ve seen cases with hydrogen of 26 at 100 minutes, and we gave them rifaximin or we gave them antimicrobial therapy, and they responded.” Just because someone had a response to treatment doesn’t mean that that lab value was indicative of the underlying cause of their symptoms. They may have had more small intestinal dysbiosis that was remedied by the antimicrobial therapy. So we should be careful not to reversely conclude, based upon treatment response, that a questionable lab value is actually the causal factor.
Rifaximin and IBS Study: Lactulose Test
DrRM: Well, there’s a paper coming out that I’m on with Pimentel and Rezaie from Cedars-Sinai where, in a small number of patients, we gave them a breath test prior to giving them rifaximin for their IBS. And in that subset—we only studied about 75 or 100 of all the people that underwent the double-blind study—there was a correlation between a positive breath test at baseline and the outcome of the patient’s bloating symptoms at the end of the two weeks of Xifaxan. It didn’t necessarily normalize the breath test. It was repeated again later. It didn’t normalize the breath test, but more people’s breath tests improved, lessened. Hydrogen/methane went down more in Xifaxan than placebo, and that is being utilized now by Salix.
I think you’ll see a movement towards A., trying to get rifaximin approved for SIBO itself and B., saying that part of IBS is a small bowel problem. And maybe we need to be more liberal and say that IBS involves the small bowel as well, particularly through dysbiosis, and that the response to rifaximin can be explained by a component or combination of small bowel and large bowel aspects. You’re going to see that evolving, based on some attempt to at least do some objective data. Because in the IBS study, the stool samples, the stool PCR, were not different pre- and post-rifaximin. There were no objective findings that showed why one patient responds to rifaximin versus placebo. There was no PCR profile in the stool, whereas here in the gas and the breath test, there was an indication that if your breath test got better, you got better.
DrMR: And this is a lactulose test, I’m assuming?
DrRM: This was lactulose, unfortunately.
DrMR: Were you able to see any trend in terms of if someone needed to have a certain degree of SIBO in order to see that effect? And this is where some of the nuance comes in. And perhaps something like an area under the curve analysis could be helpful because it tells you potentially how much extra gas is being produced in the small intestine rather than looking at one number. Is there any nuance there that you think is important to elaborate on?
DrRM: I don’t know whether I still have that paper. Let me see whether I just kept it here. Here it is. The final draft of the lactulose breath test as a predictor of response.
Here’s the abstract’s conclusion: “Patients with a positive baseline LBT result experienced significantly greater improvement from baseline in six of seven symptoms. The LBT results after rifaximin did not predict response” so I was wrong, “in the 86 evaluable patients. However, patients with LBT results normalized did have a higher response.” 76%.
So it’s a pretty mixed signal. We’re saying six of seven symptoms did improve, but LBT results after rifaximin did not predict response in the 86 evaluable patients. And let me go to that actual page now, response to rifaximin. So “a significant percentage of patients with IBS-D who had a positive baseline LBT responded to open-labeled rifaximin versus those with a negative baseline. The odds of a patient with a positive LBT responding to rifaximin was 4.3 times higher than a patient with a negative breath test, and was not affected by age or gender.”
Predictability. Here it is. “The area under the curve for hydrogen decreased significantly in rifaximin responders compared to non-responders. Few patients had excessive methane.” But the area under the curve after you gave rifaximin was significantly reduced in a responder compared to a non-responder. “And after rifaximin, 86% of patients who had an evaluable breath test…” 58 positive at baseline, 28 negative at baseline. “Of the 58 who were positive, 29% normalized after treatment. Furthermore, patients who had a positive LBT baseline that normalized after treatment showed a greater improvement in all seven individual IBS-D symptoms evaluated. However, when the response to rifaximin was based solely on post-treatment LBT results, the presence or absence of a normal LBT did not predict the outcome to rifaximin.”
So they massaged the data a lot. It means that after your treatment, whether you were positive or negative, it still went on. You couldn’t separate responders based on your post-treatment breath test. But if you looked at the area under the curve, our responders significantly reduced their hydrogen, whereas a non-responder didn’t. So you can read the paper. It’s coming out, I think, in the American Journal of Gastroenterology probably in the next month or so.
But it’s going to be a trigger to, I think, spark up discussions again. You’ll have the lactulose critiques saying, “These were done by zealots who over-interpreted the lactulose breath test,” and indeed, we haven’t all looked at the data and all objectively judged it. It was sort of done somewhere, someplace, and I was sent the manuscript. “Would you be willing to put your name on this and critique it, and be part of the authorship list?” So I didn’t really personally go over every breath test. There was only 86 done out of a huge database. But that’s the sort of stuff that’s going on. And you have to be aware that you can over-interpret. It does open the door for, “Let’s look at the small bowel in IBS.” I wouldn’t go beyond that. It may open the door for Salix to say, “We need to look at a SIBO indication.”
DrMR: And it does seem that there’s some correlation there in symptoms presentation, as assessed in correlation to a breath test. So for those with a lactulose breath test, there was a correlation to response. Doesn’t sound like it was perfect–
DrMR: –and perhaps the area under the curve methodologies… that way, you would see more of a true SIBO who has an elevation, let’s say at 60 minutes, 70 minutes, in that area. And that might diminish the false-positive effect of someone who only has an elevation at 100 minutes or 120 minutes.
And that’s where I think there is some of the evidence showing that you could make a case for lactulose, but we also want to be careful not to over-interpret. I’ll be very curious to read that study, and we’ll make sure to put that in our clinicians’ newsletter with my commentary.
DrRM: Yeah, they said the way it worked out was the greatest likelihood of improvement on rifaximin was predicted by having certainly a baseline abnormal breath test. That was a given. And if it normalized, that subset that normalized had the best response. It wasn’t 1:1:1, but…
DrMR: Yeah. And it’s not clear-cut, and one would make the natural follow-up argument that “Well, perhaps people with the highest levels of SIBO were the hardest to normalize, and so they didn’t get enough treatment to get to that response.” But there was one study published a couple of years ago that did not find a direct correlation between the level of SIBO and the level of treatment needed. So this is a little bit messy, as I think you’re alluding to, and so we want to be careful not to over-conclude.
Prokinetic Therapy: Still Useful?
Richard, I do want to move us to one more topic just because I want to make sure we have enough time to touch on this, which is prokinetic therapy. If you’re partially challenging the thinking that SIBO is a refluxing of colonic bacteria upward into the small intestine, does that diminish—in your mind—the utility of prokinetic therapy, which is supposed to prevent that from happening?
DrRM: Yeah, see, that’s why… in a way, we looked at this in our own study, which was glucose. In our own study, we felt that we could not any longer tell patients that this is all retrograde flow from the colon. But as far as in general, could we move bacteria down the small bowel better and move them towards the cecum, hopefully, minimize the retention or the chance to colonize? I think there is some traction there.
We’ve not had a very predictable and well-tolerated safe prokinetic. The prucalopride era is just arriving now with this 5-HT4 agonist being approved for constipation, and we know that serotonin stimulates everything in the gut. I suspect the first study someone will do is probably look at prucalopride’s effect on recurrent SIBO. Or something in that mode would make sense, actually. I’ve often thought about low-dose erythromycin because that’s about the only drug we think might affect the small bowel transit. We don’t have many drugs that have documented increase or improvement in small bowel transit. They’re few and far between. Cisapride might have been the last one, but it’s come and gone. So we’ll have to see where prucalopride goes.
DrMR: There was that one study showing tegaserod increased the time in which someone was SIBO-free, and I believe the second medication was used was low-dose erythromycin, which also showed an effect. Although that’s only one study, there doesn’t seem to really be a breadth of research showing that prokinetics are helpful. Is this something that you’re using in your clinic or…?
DrRM: Well, I mean, I see a lot of gastroparesis, and 65% of my gastroparesis patients have concomitant SIBO because of diabetics’ idiopathic postvagotomy. The upper GI tract is affected. There is dysmotility that doesn’t stop at the pylorus. It goes all the way down to the small bowel.
DrMR: Gastroparesis is essentially poor motility in the stomach.
DrRM: Yes, for our listeners. But in fact, it doesn’t stop at the pylorus. It goes diffusely down the gut. I explain most of my gas and bloating, in gastroparesis, is not from a slow stomach, but from small bowel bacterial overgrowth. I’m saying it’s endemic. 65, 70% of my patients have it. So I’m using a prokinetic there…
DrMR: One quick thing here, Richard, just because I want to make sure to contextualize this for our audience. Is this something that you’re seeing fairly prevalently in those with other comorbidities like progressed diabetes, or are you seeing just IBS patients with no other comorbidities that are presenting with gastroparesis?
DrRM: No, I’m seeing diabetics presenting with SIBO. I’m seeing that every day and patients come to me and say, “You’ve helped me. I have less nausea, less vomiting, but my gas and bloating hasn’t changed all that much with antiemetics or even prokinetics,” which don’t go all the way down the gut. They may stop in the duodenum like Cisapride or Peridone or Reglan. So there’s no question, there’s small bowel dysmotility. Scleroderma would be the classic. Scleroderma is epidemic with SIBO. I have patients on antibiotics almost for life with scleroderma. One month on, maybe two weeks off, one month on because small bacterial overgrowth comes back overnight in scleroderma.
So a prokinetic makes good sense to drive things down, from the stomach down. It really doesn’t separate, I think, retrograde flow. Now, in pure IBS, where the rest of the gut is theoretically intact and we don’t have mischief in the jejunum, the small bowel motility is supposed to be fairly intact. Although Pimentel has shown there may be less MMCs, but I’m not sure about that. I don’t think the standard garden variety IBS patient needs an impaired migrating motor complex–
DrMR: That’s what I’m curious about more, is how prevalent do you feel the altered MMC to be? And I can’t help but wonder if he’s obviously seeing some of the most advanced IBS cases, and in that subset, this is relevant. But what’s happening is, the SIBO community’s conflating that to all of your run-of-the-mill IBS.
DrRM: Well, if you go back to Vantrappen, 30, 40 years ago, if you had small bowel bacterial overgrowth from diabetes or any other card-carrying motility problem, he showed that after ridding yourself or treating bacterial overgrowth, best he could then, that motility amplitudes and contractions perked up and things improved. So you could argue that Mark is seeing the sort of sequelae of chronic colonization and chronic bacterial overgrowth. I don’t know about the cycle frequency. It certainly may impede the amplitude or the strength of the contraction in the bowel, but I think that’s a fairly big stretch. I don’t think anyone else has really even remotely gone there as far as the migrating motor complex world. That’s a huge jump, I think, beyond that.
I think it could decrease the amplitude of contractions and it could plant a seed for a weak or more impaired bowel, and therefore, could make you more willing to aggressively eradicate the small bowel to try to perk up the contractions that you can. I use that theory in diabetics and other people that already have a very weak MMC. If I can perk up their contractions by continuously treating the SIBO with antibiotics, can I improve the strength of their motility?
DrMR: Yes, that’s exactly the hypothesis.
DrRM: That’s what I try to do. You could argue treating constipation, certainly with a pro-motility agent, would prevent retrograde tendencies in the distal ileum. I think we’ll have to stay tuned on the larger picture. I’m more focused right now on giving someone apple cider and vinegar and trying to restore the acidic content of the small bowel. I think the acidic environment of the small bowel is very important and the PPI use is rampant. And patients could be born with hypochlorhydria. We don’t know what the gastric acid level is on a given day, and I tend to over-acidify the small bowel as a very simple method of trying to discourage and create a hostile environment, for bacteria.
DrMR: And I’m so glad you said what you just said, which was you essentially treat someone to keep their symptoms at bay and you should see a resultant improvement in motility after doing that. That’s something I’ve said multiple times, and that’s the approach I have fallen into. Because we do know that the interstitial cells of Cajal do have regenerative and plastic ability, meaning that they can repair if you’re creating a less inflammatory environment. So if you get the patient healthy, often times the motility will fix itself.
And just one other comment, if anyone else in the audience is wondering about Pimentel’s IBS smart test, which has been shown to correlate with IBS… I wonder how relevant that finding is, if we were to look at it in six-month or one-year follow-up. Meaning that what I assume will happen in a fair number of people—and I could be totally wrong here but it’s just a posit—is that the longer we go in terms of a patient having little to no symptoms, the better the IBS smart results look. With the exception of a small subset of very, very advanced cases that may need other therapy.
Richard, hypochlorhydria. I’ll make this the final thing we touch on. Sorry to keep you on the line here a long time, but there’s just so much–
DrRM: It’s all right.
DrMR: So how do you feel about assessing this? There’s different tests, we know, in terms of risk profiles that patients who have hypothyroidism have. Maybe a 20 to 30% incidence of antiparietal cell antibodies, so that might be one subset that we want to look more closely at. And there is data showing an increased prevalence of SIBO in hypothyroid patients. Are there other markers, somewhat practical markers, that you look at in order to assess this?
DrRM: Well, I think the simplest one is a serum gastrin, if you’re not on a PPI (which will definitely contaminate the interpretation). For the serum gastrin, less than 70, less than 60 is normal. If you’re hypochlorhydric, gastrin tries to get revved up to try to overcome that deficiency, make more acid for you, and try to restore you back towards normal. So if you cut the vagus nerve or if you are hypochlorhydric, your serum gastrin, as in pernicious anemia, which in the extreme case is over 1,000… If it’s somewhere around 75 to 100, 150, it could imply that your gastrin is being revved up to try to compensate for hypochlorhydria. So that’s a poor man’s test, a serum gastrin. If you can find someone who’s not on a PPI these days, which is sometimes very hard to find. But that would be one test.
The other is that if you end up endoscoping these folks for whatever reason, biopsy their stomach and their antrum and look for signs of small bowel intestinal metaplasia. Any signs that they have small bowel mucosa overriding or mixing into the antral mucosa or you’re seeing what’s called atrophy. You see that the fundic glands are becoming atrophic and you can see lots of veins coming through in the mucosa (so-called mucosal atrophy) which occurs after years of H. Pylori. So if you have burnt-out H. pylori that has not been treated for years or was treated but still caused a lot of trouble before you got to it, that will impair your parietal cells and you will end up as a hypochlorhydric individual. They’re the ones that go on to gastric cancer in South America and China, which is a long-term natural history of H. pylori. Here in this country, it’s been arrested and aborted but hypochlorhydria may still be present from years of H. pylori. And those are the patients that may be vulnerable for bugs to flourish in the proximal small bowel and lead to the symptoms of SIBO.
DrMR: I’m so glad that you made this remark because I’d really like to get your perspective on this as a boots-on-the-ground clinician. I looked into gastrin a few years ago. UpToDate has a fantastic summary. For all the clinicians out there, UpToDate is a great resource. And from what they put together, they concluded that gastrin doesn’t seem to be reliable in H. pylori. And then depending on the region of atrophic gastritis (one of the causes of low stomach acid) you may see an increase or a decrease in gastrin. And when looking at that, it looked like it would be very hard to reliably read gastrin. You did refer to it as the poor man’s marker, so that kind of alludes to that it may not be perfect…
DrRM: Well, it has to evolve into the body, see. H. pylori starts in the antrum. So in the beginning, it may not be particularly visible. But as it evolves, it sneaks up into the gastric mucosa in the body and starts to impair the parietal cells and the gastric acid cells. So yeah, it may take a little bit of a career of H. pylori to become hypochlorhydric, unless you’ve got the antibody people, who are walking around with parietal cell antibodies. And then, they will have a higher gastrin level than other patients. But this is a 75 to 150… It’s in the lower half of gastrin elevations and nowhere near pernicious anemia.
But it’s a poor man’s test. If you get endoscoped, it would be worth convincing your endoscopist to biopsy the stomach not just for H. pylori, but to look for early signs of small bowel metaplasia.
DrMR: And so would you be asking just for small bowel metaplasia or would you ask them to check for atrophic gastritis? Is there a more efficient way of communicating this?
DrRM: Well, yeah, that’s right. You’d like to see a bit of both. Some atrophic changes and maybe on top of that, in a subset, the evolution of small bowel tissue or metaplasia surfacing or co-inhabiting the gastric mucosa. But atrophy would be important, I agree.
DrMR: Okay. And so one more time on the gastrin, because some of the people listening to this also are going to be patients who may just be doing some of their own lab panels and are their own advocates. So is there a certain level at which you would say, this person should be on some type of acidification treatment? Either supplemental hydrochloric acid or–
DrRM: Well, certainly above 100 is the teaching we all had. That’s hypergastrinemia. But if you look at the average citizen who’s running 35 to 65, 70, that’s pretty normal. We probably all run that. I think anything above 70, 75 is that upper 10%. And you could argue they’re the ones that either came into the world with a low acid, maybe they’re the ones that go on to become a gastric ulcer with their H. pylori and they’re the ones that long-term are vulnerable to hypochlorhydric problems, where they get giardiasis if they go to Mexico. Prone to gastroenteritis because they can’t kill bugs in restaurants. That might be the hypochlorhydric group.
DrMR: Okay. Well, Richard, I want to be respectful of your time or at least maintain a shred of respect since we’ve already gone about an hour and a half here, but I really do appreciate it. I think this was a fantastic conversation, very insightful. I appreciate the academic rigor and objectivity you’re trying to bring to some of these more controversial topics. Is there anywhere that you want to point people on the internet or anywhere if they wanted to read or hear more from you?
DrRM: No, I don’t have any sort of massive review article. I think our two articles I think are unique in that we’ve taken the time to do those cultures I talked about, and one is actually in one of our prominently read journals, Neurogastroenterology & Motility. It’s a journal that’s put out by the American Motility Society. It was published in 2018, this article, which is an attempt to try to separate breath testing from the real data, how many bugs are in your gut. And the other one was published in the journal called BMC Microbiology back in 2017, which looks at the human jejunum as an endogenous microbiota that differs from the microbiota in the oral cavity and colon, just trying to separate out parts of the gut.
But I would certainly encourage our listeners to keep an open mind. There are many of us who are contributing. We’ve all got a part of it or a segment of it. We have our little sort of theories, and slowly we merge and meet, and we’ll get a unifying theory with time. But I think, to be fair, things have moved from blaming everything on that bad colonic flora has gone north and taken over the jejunum. I don’t think that’s where the tide is going. I think the tide is that the upper half of the gut has its own unique bacteria and microflora, and that can become a problem. The colon can have its problems too as in C. diff and fecal transplants. That’s another issue. But the upper half, it may have its own problems too, but it may need to be looked as not an extension of the colon.
DrMR: Well, I think that’s very, very well-said and again, thank you for the conversation. I really appreciate it.
DrRM: Well, let me say, it’s been a real pleasure speaking with you, Dr. Ruscio. You’ve obviously got great knowledge and it’s been a great interview. You’ve done great homework and it’s a pleasure to be around a colleague such as yourself, and I hope your audience has enjoyed both of us.
DrMR: Yeah, thank you again.
DrRM: My pleasure. Any time.
What do you think? I would like to hear your thoughts or experience with this.
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