Gut Microbes – PediaCast 243

Dr Sandra Kim joins Dr Mike in the PediaCast Studio to talk about the intestinal microbiome. We’ll cover the good organisms and the bad ones. How do one trillion tiny creatures living inside each of us affect daily health? What is their relationship with inflammatory disease and chronic illness? How do we get rid of the bad and replace with the good? All this, plus the hottest topics in the world of gut microbe research.

Topics

  • Gut Microbes

  • Good Bacteria

  • Bad Bacteria

  • Probiotics

  • Inflammatory Bowel Disease (IBD)

  • Microbiome Research

Guest

Links

Transcription

Announcer 1: This is PediaCast.

[Music]

Announcer 2: Welcome to PediaCast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike!

Dr. Mike Patrick: Hello, everyone and welcome once again to PediaCast. It's a pediatric podcast for moms and dads. This is Dr. Mike coming to you from the campus of Nationwide Children's Hospital. It is episode 243 for February 20th 2013. We're calling this one Gut Microbes.

So welcome everyone to the show. Gut microbes, what does that mean? Well, we are talking about microorganisms that live in our intestinal tract and their relationship to our health and since this is a pediatric podcast, to the health of our kids.

There's a lot of them in there to the tune of one trillion little creatures living inside each of us. Isn't that a great thought? And they affect our health in both good and bad ways. We've all heard of good bacteria and bad bacteria.

So today we're going to explore what makes one microbe good and another one bad. And we aren't limiting the discussion to bacteria, we'll also consider viruses and worms and fungi. OK. Worms aren't technically microorganisms, I realize, but if we're talking about little creatures in the gut moms and dads expect us to include them so we'll mention worms as well. But mostly we're going to be focusing on bacteria.

So all these microorganisms, how do they affect the normal function of our intestinal tract? What jobs do they have? What problems do they cause? And how do we get rid of the bad ones and introduce and encourage growth of the good ones? What role do they play in chronic illness like inflammatory bowel disease, but also things like obesity and diabetes? What advances are allowing us to study this world of microorganisms that's living inside each of us? And what's the latest in gut microbe research?

So we have a big show lined up for you today with lots of questions to ask and details to cover. And to help me do that we have a delightful and dare I say high energy studio guest with us today, Dr. Sandra Kim, MD, is the Medical Director of the Inflammatory Bowel Disease Center. We'll do the whole exact title here as we officially introduce her.

Suffice it to say she's a pediatric gastroenterologist, a GI specialist here at Nationwide Children Hospital. So we'll get to all her credentials in a moment.

02:45

Before we get to Dr. Kim, a couple of quick reminders for you, the 2013 Pediatric Pearls Conference and this is going to be for the clinicians out there, so doctors and nurses, nurse practitioners, it is coming up Thursday, March 28th from 7:30 in the morning until noon here on the campus of Nationwide Children's.

On the agenda health care reform, long-acting contraceptives, vesicoureteral reflux management and cholesterol screening recommendations. If you're interested in going to that, you can check out the registration link in the Show Notes that takes you to the Education Portal on our website and then under Professional Courses you want to select "For Physicians" and then click Search for Courses and the 2013 Pediatric Pearls Conference will be one of the first ones that listed for you.

Another reminder, this one for parents, PediaCast is on Facebook and Google+, but I think where we really shine is Pinterest. If you haven't checked this out on Pinterest I would encourage you to do so. We have that Episodes board where you can repin shows with topics matching up with your interests. We also have a News Parents Can Use board covering topics and stories not included in the podcast.

And then we have a Blog board where you'll find and can share some of my writings. And a new one just popped up, the Entertaining Your Kids board, which we talked about last week so be sure to check that out as well.

The other reminder, PediaCast is your show so if you have a topic you'd like us to talk about or if you have a question for me or want to point me in the direction of a news story you can do that, just head over to pediacast.org and click on the Contact link.

Also I want to remind you the information presented in every episode of PediaCast is for general educational purposes only. We do not diagnose medical conditions or formulate treatment plans for a specific individual. So if you do have a concern about your child's health, make sure you call your doctor and arrange a face-to-face interview and hands-on physical examination no matter what you've heard in this program.

Also your use of this show is subject to the PediaCast Terms of Use Agreement, which you can find over at pediacast.org.

All right, let's take a quick break. We'll get Dr. Kim settled into the studio and then we'll be back to talk about gut microbes. And it's all happening, right after this.

[Music]

05:24

All right. We are back and Dr. Sandra Kim, MD, is joining us. She is the Medical Director of the Center for Pediatric and Adolescent Inflammatory Bowel Disease, I got it right that time, at Nationwide Children's Hospital and an Associate Professor of Pediatrics at the Ohio State University College of Medicine.

She also a nationally recognized expert on the world of the microorganisms living inside each of us and she joins us today to talk about these tiny creatures. So there's a lot to say on this subject so let's get right to it with Dr. Kim, welcome to the program.

Dr. Sandra Kim: Thank you so much!

Dr. Mike Patrick: I appreciate you stopping by. First things first, you attended medical school at the University of Michigan and you are now affiliated with the Ohio State University College of Medicine. So my question is, is that allowed?

Dr. Sandra Kim: Well, I have to be politically correct because I'd like to keep my job. Let's just say that I am a former Columbus native and a graduate of the Columbus School for Girls, went to Ann Arbor and said I was never coming back to Columbus, which is why I'm here now. So we'll love the hospital, we'll support the institution and I'll still be "GO BLOW".

[Laughter]

Dr. Mike Patrick: Yeah and like you said you want to keep your job so we'll just stop right there. Both great institutions, University of Michigan and Ohio State, and is really proud to have both of them in the big 10.

Dr. Sandra Kim: Absolutely!

Dr. Mike Patrick: So what is meant by the term "gastrointestinal microbiome"? It's kind of a new term that we use. What does it mean?

06:51

Dr. Sandra Kim: Absolutely! So let's break this down even a little bit more. So we say gastrointestinal, so we're talking about the classic GI tract. So what we know is our intestines, our stomach, etc. But when we talk about microbiome, I just want to sort of clarify between a similar term that folks may have heard called microbiota.

So microbiota mean the actual microbes, so that can be bacteria but also things like viruses, fungi, etc. The microbiome refers to the collection of both the microbes but also genes that are associated with these microbes in terms of functioning that reside within the body.

And when we say gut microbiome, this focuses specifically in the gastrointestinal or GI tract. But there are other microbiomes that we talk about when we talk about humans, whether it be the skin, the mouth, the urinary tract. So there is the collective microbiome and the focus of today's discussion which will be the gastrointestinal microbiome.

And one of the things I want to bring up because I think if a lot of folks had talked about bacteria and viruses even let's say five, six years ago, we would have just talked about individual bacteria, right? But there's been much more of a focus, not just on individual microbes or bacteria or viruses, but how the collective group interact.

And what's really been sort of revolutionary, in terms of how we see the microbiome, have been several national and worldwide collaborative projects, meaning multiple centers come together. And one big one that I really want to emphasize is the one that's been funded by our National Institutes of Health back in 2007. And what this has done is really expand how we see microbes.

And so it has been a collective of utilizing new and more powerful techniques to identify and catalogue not only bacteria and other microbes but the genes associated with these microbes, but then to look at this as a collective. So something called "metagenomes", for instance, big long word but what it means is the collective of microbes and the genes associated with them within an individual, so there are over 700, and also looking at all the different species.

I think, Dr. Mike, you had referred to how there are trillions of bacteria. So we say can be anywhere from 10 to even 100 trillion bacteria in your body. So when you look at the cells that you have in your body and you look at bacteria, the bacteria and other microbes outnumber our human cells 10 to 1.

So I always like to tell people that the microbes are kind and considerate enough to let us reside in our own bodies.

[Laughter]

09:35

Dr. Mike Patrick: Now, when you talk about this collection of microbes being the microbiome, I'm assuming that then microbiome is different from person to person. And what advances have enabled us to study the individual organisms so that we can tell which ones are in each of us?

Dr. Sandra Kim: No, absolutely. I think what's been really incredible and this is again the power of collaborative medicine and collaborative research both in the United States and in fact one of the seminal folks involved in this has been the group at Washington University, headed by Dr. Jeffrey Gordon, funded by the National Institutes of Health or NIH, as well as other organizations like the Crohn's and Colitis Foundation where they first developed more powerful molecular microbiology tool.

So what does that mean? So traditionally and I think I want to give an example to our listeners, so let's say your child may or may not have strep throat, so your doctor takes a swab, swabs a throat, streaks it on a plate, they send it to the lab, they say yes, there is strep growing or no, there isn't. So when you think about that that might be easy for individual bacteria, but when you're talking about a whole collection of trillions of bacteria, first of all it's going to be difficult to identify specific bacteria better than others; and secondly, there are so many bacteria that are really picky about the environments they grow in.

So what we've been able to do with this new molecular tool is to actually look at the DNA, when you extract it from different sort of samples, whether it be stool, whether it be biopsy tissues or urine, for instance, and you're able to actually detect what we would call bacteria that could not be cultured routinely, and then taking some of that information there has been the second step where instead of taking that very tedious process or just culturing at one bacteria, what we call faster deep sequencing, which takes the DNA that we can extract and we can look at multiple types of species of bacteria and we can get the information more quickly.

And then the third step, this term called "bio informatics". So what does that mean? So sort of in nutshell, we have folks who are able to develop powerful computerized tools that help us analyze this really crucial data that's being generated by looking at DNA, by identifying sort of families and groups of bacteria so that we can understand not only whether certain bacteria are or aren't present but seeing the relationship and the relative sort of diversity or lack thereof of the different types of organisms in your intestinal tract.

We can then take this information and look at different areas, meaning you can always just study a human so there are unique cellular type of models where we can test potentially the effects on cells, mechanisms and there are special types of mice and in fact this was part of my research in a not so past life where we can take special mice that have certain genetic properties, you can actually raise them germ-free. It's what we called sort… environment and then you can test the effects of certain bacteria and certain genes in these mice and see what may happen from a mechanistic standpoint.

12:53

Dr. Mike Patrick: Very interesting.

Dr. Sandra Kim: So I know threw a lot, but the bottom line is that's the beauty of taking tools on multiple levels and trying to get a better understanding of disease.

Dr. Mike Patrick: If we have all these different organisms and each of us sort of have it as a different collection of organisms, because human babies born without any bacterial in their intestine, right? So I guess how do they get there and then throughout a person's life what determines which group of bacteria are going to be living in a specific person?

Dr. Sandra Kim: Great question! So as we say you very, very astutely point it out that a baby is technically "sterile", but just the process of being born already starts colonizing the baby's intestinal tract, the skin, the mouth, all the different parts of the baby and so it actually starts at the of delivery.

So for instance, how a baby is delivered will affect what types of bacteria are more dominant within a baby at the time of birth. So for instance, C-section or Caesarian section versus normal spontaneous vaginal delivery. And then what you feed your baby, whether it's breastfeeding or formula feeding will also affect what types of bacteria microbes will populate the intestinal tract.

And then during the first few years of life not only diet, not only how the baby was delivered, but whether the infant had been exposed to certain medications specifically antibiotics will also make changes. So we know with very sort of strong studies from groups in Puerto Rico, in the United States that the development of the bacterial composition in a baby's sort of GI tract will be pretty much set and similar to what it'll be like as an adult by the time they turn three. So you can see that just day zero things are already developing.

Dr. Mike Patrick: Yeah. Do we also see similar microbiomes for people who live in the same house or the people that we're in close contact with do we share their microbes?

Dr. Sandra Kim: I know. We always say share everything, right, in the family. So there are definitely similarities but it's not absolute and that's what tells and we're going to talk about this a little bit later and why there are differences, there is still what we call person to person differences. So definitely similarities, so we know things like environment and diet are crucial in shaping what types of bacteria you have. But remember we're already saying that by the time you turn three things are pretty much reset.

So for instance, family members may have had slightly different things early in life, how they are delivered, formula, what antibiotic exposure, so that's one thing that causes some variations. And then the other thing is genetics and we'll also talk about that a little bit that while genes aren't everything there are lots of genes that affect how your body deals with bacteria and how it fights bacteria and what its responses are.

So clearly, similarities because of the environment but there are still going to be some differences.

16:09

Dr. Mike Patrick: Sure. And when we talk about "good microbes" and "bad microbes" for the organism it's just trying to live its life.

Dr. Sandra Kim: Yeah. Absolutely.

Dr. Mike Patrick: Not intrinsically good or bad. But what is sort of meant by those terms? What makes something good versus bad?

Dr. Sandra Kim: So first, I am reminded by a professor of mine in medical school, Dr. Jerry Abrams, who told us that the colon and the intestinal tract is one big happy social organism. So what that means is just as we have to co-exist at work or in our families, with the other folks around us hopefully, the same goes for bacteria.

So I think when people hear, let's give an example, E. coli versus probiotics like lactobacillus, it becomes very black and white, E. coli must be bad, lactobacillus must be good. But the reality is it's much more shades of grey. But classically, we know that there are typical or some bacterial species that have been traditionally considered to be more of our good or protective type of microbes and I'll give a few examples.

Some of the names I'm going to mention if folks are on probiotics they've probably read on the labels. So lactic acid producing bacteria, so examples are lactobacillus, bifidobacteria. So you're already starting to think I think I've seen those names before and why and so these are some of the bacterial strains along with saccharomyces boulardii, streptococcus salivarius that are traditionally found in some of the different preparations of probiotics that are produced and sold in this country.

And so another bacteria for folks who are familiar with the Crohn's disease literature is something called Faecalibacterium prausnitzi, we call it F. prau or F. prausnitzi. And it's been found that patients who have Crohn's disease, in most studies, but again it's not absolute, have a decrease in this bacteria and so the question becomes could this also be a potentially protective bacteria that may be useful as we look forward in the future for treatments.

18:16

Dr. Mike Patrick: Sure. OK. So we named these ones that we see and recognize but what impact do these good ones have in our intestinal tracts? So what are they doing that's good?

Dr. Sandra Kim: So people always ask, I take a bunch of these as a probiotic, I try to repopulate my gut, what is it doing? Why are these important? So that's one of the crucial pieces that we are still trying to do, not only as clinicians but as physician researchers, not just trying to say that there is an effect and therefore we're done with it, we want to know mechanisms.

So some of the potential mechanisms could include the fact that some of these bacteria, this lactic acid or lab bacteria change the PH or acidity in the GI tract. So the thought is if you change the PH, make it more acidic, then you are able to kill some of the more inflammatory or aggressive bacteria.

And the feeling is that there is a particular group of bacteria, what we call Gram negative rods. So what are those? Examples like E. coli, for instance, is a Gram negative rod and we know lots of E. coli can cause problems although not all of them.

So the thought is (a) they help kill bacteria; the second thought is that some of these bacteria, including that F. prau that I talked about or F. prausnitzi, produce something called short-chain fatty acids. So what are SCFAs or short-chain fatty acids? You know, people ask me that. And short-chain fatty acids help provide nutrition to some of the cells that line your intestinal tract, especially the colon.

So again, there may be a nutrient component. And then some of these good bacteria may stimulate certain types of chemicals that white blood cells produce, what we call cytokines, but cytokines can be protective or they can cause damage. And so some folks feel at least not so much in human studies yet but at least in studies where we look at mice and cells that they may stimulate the production of more of these good chemicals or cytokines.

20:17

Dr. Mike Patrick: Sure. And in talking about PH, I know some enzymes that our body uses to break down food may need a specific PH range in order to work. So if you have the right mix of bacteria then that may help your PH what you need for the enzyme to work correctly.

Dr. Sandra Kim: Sure, in activation. And that's why I think it's not a matter of having the bacteria there per se, but what affects it actually has on how the body functions. And I think that's something important for our listeners to remember because I think one of the things that happen folks assume that if a bacteria is good it's always going to be good and protective and if it's bad it's always bad.

And that's where, let's go back to that definition of the microbiome again. It's not just about the bacteria and other microbes. It's about the genes associated with functioning. So just because you have a certain bacteria, for instance, sitting there it also depends on what genes are turned on or off, what enzymes are affected or not and that's why it's so important to understand not only the presence or absence of those bacteria, but in what situation certain genes are or aren't turned off.

Dr. Mike Patrick: Sure. So these microbes, these so-called "good ones" have multiple functions inside the GI tract. How do they affect our overall health?

Dr. Sandra Kim: That's a great question. So first of all, if they are helping, for instance, stimulate production of these more protective chemicals or cytokines, the thought is that you will have protection against sort of setting off that inflammatory cascades. So that whole sort of collection white blood cells being stimulated and more of these inflammatory cytokines or chemicals being stimulated and with less inflammation you get less swelling.

For instance, if you are talking about someone with a GI disease less inflammation in the intestinal tract. Some of these good microbes, the question's we don't just have good versus bad microbes in the body but rather that balance. So the balance is keyed more towards these good or protective bacteria, the thought is that it could be protective in terms of developing certain types of disease and it may also be important in things like nutrient absorption and metabolism.

So the thought is that this balance or the relative sort of proportions of the different bacteria may help you be more or less efficient in terms of how you utilize nutrition and calories.

22:39

Dr. Mike Patrick: Sure. So obviously these are good things and we want those bacteria in our intestine. How can we introduce and encourage the growth of the good guys?

Dr. Sandra Kim: A lot of different things. One is actually adding probiotics. But the only problem is if it can only be so simple. And so we say probiotics are good, we'll talk about that a little bit. But what we want to do as we move forward as clinicians and as researchers is not only say let's just give you some probiotics that we think may be good but figure out the best combinations.

Other ways, and this the difference between pro versus prebiotics, there are certain food products that we call prebiotics, so it's not a typo when you see pre. Prebiotics are food products, things like what we call oligosaccharides, so carbohydrate derivatives that help foster a very happy environment for the probiotics to grow within the body.

So in a perfect world if we could figure out the right combination of pre versus probiotics then that could help not only add the probiotics but allow them to be sustained and not just go away after they are introduced. That's one example.

Dr. Mike Patrick: Yeah. Sure. So antibiotics is going to be a chemical that kills bacteria.

Dr. Sandra Kim: Yes. Right.

Dr. Mike Patrick: Probiotic is actually good bacteria, so you're taking the bacteria.

Dr. Sandra Kim: Exactly. Right.

Dr. Mike Patrick: Like when you think of a probiotic pill, so this has live bacteria in the pill, and you may not know the answer to this, it just sprung up in my mind and I'm sorry.

Dr. Sandra Kim: Yeah. Not a problem.

Dr. Mike Patrick: So if you have live bacteria they have to have something they have to have something that they're using for energy or they're dormant when they're in the capsule form?

Dr. Sandra Kim: They're dormant and so you get the probiotics, so the thing is they're alive, they get into the GI tract, but this is the beauty of the prebiotics because that's one of the things that people wonder with the relative efficacies of probiotics. And that's why we're saying the prebiotics to provide the fuel and the nutrients that the probiotics need to multiply.

And then the question becomes if antibiotics, do we combine this depending on the person and the situation of doing selective targeting of certain more harmful bacteria to then sort of make this work together and to repopulate the gut.

25:01

Dr. Mike Patrick: Yeah. Because if the probiotic, if you take the pill and were the granules or whatever and they don't activate…

Dr. Sandra Kim: Yeah. Or they don't survive then they're in the GI tract, but really you're not doing it for like, it's not like taking an Advil and saying OK, I have a headache, I'm going to take it, it goes away. The goal really is to try to repopulate the gut. So in a perfect world we want to get them in there, we want to help them flourish and maintain and then depending on the situation we need to figure out if we need to get rid of some of the other more aggressive bacteria that may prevent the probiotics from thriving.

Dr. Mike Patrick: Sure. Now this prebiotics then, what are some specific examples? What are some good foods to eat when you're trying to encourage probiotics to grow?

Dr. Sandra Kim: It's funny. You know right now that's what we're still trying to figure out, but certainly oligosaccharies inulin is something that you can see in certain yogurts. Sometimes inulin is added so we get what we call an oligosaccharides, so it's a type of carbohydrate.

Some folks have recommended things like psyllium, so again, if you are like me and most people aren't and you read your bran cereal and all your fiber sort of boxes you'll see that psyllium is a source of fiber. And I think as we approach this as a clinical and a medical community trying to figure out other types of foods that could fall in the prebiotic category that we could use to supplement.

But I think that brings us even to the question of diet and effects. So you'd ask what we can do to foster the growth of more of these protective or good bacteria. And this comes to the sort of the thought that you are what you eat. So there's a reason your parents actually told you that, specifically your moms, maybe not.

So I preface this by saying I don't want folks to get the take home message that Sandy Kim said that if you have something inflammatory it's because what you ate, that is not the message. But it is very clear, especially with recent studies, again, looking at the human microbiome, showing the power of a collaborative and all the new tools that we have, is that there are things that affect the development of the types of bacteria.

And I'll quote just a few interesting studies just to give you all a picture of why we say that while more research needs to be done, this is starting to give us directions. There have been a few series of studies within the past year to two years that compared kids and these were European children, but children who ate more of a Westernized processed diet versus children in West Africa that had a more traditional West African non-processed type of diet.

And these are completely healthy kids, no inflammation nothing. And the researchers looked at the stools of these children and what they found is that there were obviously person to person differences across the board, but some trends that were seen included the fact that as a whole the children who ate a more Westernized European very similar to the U.S. diet had higher relative proportions of what we'd consider more aggressive type of bacteria. Not enough that they were having infections, but things that we would associate with the GI tract infections like E. coli type of strains.

Whereas the children in West Africa in Burkina Faso had higher proportions of more what we would call our traditional probiotic or protective type of bacteria that produce the short-chain fatty acids that I talked about that are important to provide nutrition to the cells that line our intestinal tract.

28:43

And then another beautiful study elegantly done by a large collaborative of both researchers at Washington University, at the University of Pennsylvania, as well as colleagues in South America and Africa found that (a) your diet really did affect the composition of your gut, but things are pretty much decided by age three; and secondly, you could cluster sort of the groups of bacteria based on where you live, so they compared children to adults who grew up in the United States versus West Africa versus the Amazonian River Basin and found that if you look at the clusters and types of bacteria much closer with the folks from South America versus Africa and that really the folks here in the United States were the outliers, same sort of concepts.

So while eating itself does not cause you to have disease this brings us sort of to the concepts that if we could make a healthy impact could that help the folks who are unfortunately predisposed to developing certain types of disease?

Dr. Mike Patrick: So do you think if you took a kid who grew up in Africa and had a specific diet and then had a specific microbiome and then they moved to the United States after the age of three, do you think a drastic change in diet would have an effect?

Dr. Sandra Kim: It's interesting. The basic what we would call enterotypes of that, term was coined by folks who studied microbiome that the basic composition and proportions of bacteria are basically determined as we said by age three. But a classic study was shown by a group at the University of Pennsylvania in conjunction with the folks at the Children's Hospital of Philadelphia showed that while your enterotype really do not change much by even small changes with fat content, for instance, the amount of carbohydrates, you could make subtle changes in some of the sort of the levels of certain types of bacteria so that you could make an impact.

But if you reverted back to your normal diet it would basically revert back to what your original composition was. So this does tell us that even as an adult you can make alterations, you can change basic things even if you can't think change everything.

Dr. Mike Patrick: Yeah and there are so many other advantages to lowering your fat intake and increasing your fiber.

Dr. Sandra Kim: Exactly. Oh yeah. Good for your heart, I know. I was focused on the gut, but by the way you've got to worry about your blood pressure and your heart, too. But that really actually explains why certain diseases we thought were just genetics actually has more of a subtle component where the prevalence of getting certain types of autoimmune disease is actually changes if you move from one country to another and then compare with the folks who are already in that country. So yeah, genes and bacteria and the environment.

31:37

Dr. Mike Patrick: Yeah. All mixed together. What about gluten? It sort of become a fad now to avoid gluten. So I'm not really talking about people with like celiac disease, but just folks who would think that they feel better when they eliminate gluten from their diet. Do you think that's an inflammation from the gluten itself or is it an effect on the microbiome and then somehow that affects how you're feeling?

Dr. Sandra Kim: So the folks that look at celiac disease and people who look at the microbiome just with any type of autoimmune or inflammatory type of disorder the question is are there alterations just from having the inflammation itself. The answer is probably yes.

And then the other question because we know that even with celiac disease and we'll talk about gluten intolerance in just a second, that even with celiac disease not everybody, even if you've got the genetic predisposition, just happens to develop it at birth. I mean, some folks develop it early in life, but other folks develop it at times of stress.

So we always say the classic sort of presentation of celiac disease is someone who's already got the genetic predisposition is the infant to toddler who goes from being formula fed to having table foods introduced with gluten. Classic presentation.

But there is also a subset of folks who develop it later in life and often it's associated by certain stressors, so could it be something infectious, could it be something else that causes sort of a break in your intestinal barrier causes that inflammatory reactions. So clearly, I think it's a combination.

So then what about the subset of folks who feel that gluten causes GI upset? It very well may because it is a protein and it may not just be gluten. There may be other proteins that may also cause upset, too. Because again, even if it's not celiac disease we know that if you have sort of what we call an antigen, means it's like a protein component that may trigger an inflammatory response.

Dr. Mike Patrick: Yeah.

Dr. Sandra Kim: Even if it's not celiac disease you may have sort of that low grade sort of response and have the symptoms associated with it.

33:32

Dr. Mike Patrick: Yeah. So let's shift gears a little bit and talk about the so-called bad microbes.

Dr. Sandra Kim: Sure, because that's was the basis of what my research has been.

Dr. Mike Patrick: Yeah. Yeah.

Dr. Sandra Kim: And my clinical interest.

Dr. Mike Patrick: So what are some examples of the bad guys?

Dr. Sandra Kim: OK. So the bad guys are ones that I think actually people are probably more familiar with, E. coli. But again, let me stress not all E. coli are created equally. And so there is the classic E. coli that we call the E. coli that comes about when you got to the petting zoo and your kids like pet the wrong animals, they get the E. coli, they get bloody diarrhea.

There are different types of E. coli and different sort of type of symptoms. C. difficile or C. diff that is commonly known as another unpopular bacteria, so to speak, that can happen in folks, especially if their immune system doesn't function well or if they've been on a lot of antibiotics and it's kind of wiped out their gut. Those are a couple of examples.

And then I always say that independent of that bad bacteria or bad microbes anything that just overtly causes an infection in my book is pretty much a bad player.

Dr. Mike Patrick: Yeah. So salmonella, shigella.

Dr. Sandra Kim: Yes. And that to me is just sort of a given.

Dr. Mike Patrick: Yeah. Yeah. Yeah. And then there are also viral intruders. Are there any viruses that are OK in the intestine?

Dr. Sandra Kim: You know, typically, this is where we are still in the process and that again is the beauty of the human microbiome project. That's been a really focus in study. And we always talk about it if we're going to talk about bad viruses all I have to say is cruise ship and we think of Norwalk virus or what is known as Norovirus.

Rotavirus without question, especially folks who have had infants, who have kids in daycare, those are all viruses that attack not so much the colon but the small intestine causes inflammation, you get the bad diarrhea because you're not absorbing and then even after the infection clears you still have the problems with the inflammation that's clearing.

But what's even more interesting is what is the relationship between a virus and a bacteria and this is where folks are looking not just from an infection standpoint, but looking at certain inflammatory disorders like Crohn's disease and all sort of colitis, seeing if it's sort of that two to three-hit theory where you have let's say a viral infection, which causes inflammation that changes things in the intestinal tract then you may or may not have over the growth of certain bacteria; and someone who's genetically susceptible and then you develop disease.

So that's something that has been a very clear focus and I can tell you that there are actually consortia right now in some of the top sort of GI microbiology research groups that are actively investigating that a little bit more in detail.

36:15

Dr. Mike Patrick: Sure. I had mentioned worms and so this is the place in the talk to mention them. So they're not supposed to be there either.

Dr. Sandra Kim: Yeah, hopefully not. And as your friendly GI doctor I don't like seeing them, but…

Dr. Mike Patrick: And we have talked about pinworms quite a bit on this program. There are also roundworms and tapeworms and then you can look it the eggs in the stool under a microscope to diagnose that.

Dr. Sandra Kim: So yes. But then I thought you're going to actually ask me the question could worms actually be good. And so absolutely no one likes worms, myself included. We know that they can cause different symptoms, sometimes just with the GI tract and sometimes even if they enter through your body, end up in the GI tract, they can sometimes move to other parts of your body and affect things like your skin and your liver and even your lungs.

So I know that we're already starting to get some folks here that have that visual pictures.

Dr. Mike Patrick: Squeamish. Yeah. That sort of larval migrants kind of thing.

Dr. Sandra Kim: Exactly. That's what I was thinking and I'm already starting to get a little uneasy here. But let me tell you, there were also studies that looked at worms and specifically worm eggs or larva in treatment of certain inflammatory diseases, so with Crohn's disease for instance.

And so the theory behind that is that there are different types of immune responses and that the immune response or inflammatory response that is the stronger one in Crohn's disease, which is an inflammatory disease of the GI tract that's chronic, can be counterbalanced by giving worms that sets up more of another inflammatory pathway that is more of an allergic type of phenomena, but it can counteract some of the chemicals or cytokines that we talked about.

And so for some of my listeners here who are unfortunately familiar with Crohn's disease or ulcerative colitis, you may have read about using worm therapy or helminth therapy. Right now there are certainly good theoretical reasons. It is definitely not ready for primetime.

The study's still need to be done certainly in adults. Folks in Europe are looking at that and certainly we have colleagues in the United States who are spearheading certainly the basic science or animal type of studies and starting to look at patients as well. So more to come with that. I just thought I would mention that for anybody who may have questions.

38:41

Dr. Mike Patrick: Yeah. Absolutely. That's great. I thought you were going to say a tapeworm, like it would be good weight loss program.

[Laughter]

Dr. Sandra Kim: Yes. I think as a pediatrician I may get in trouble with the Infectious Diseases Department.

Dr. Mike Patrick: Yeah. Yeah. Absolutely. A disclaimer, folks, I was not suggesting that. It was a joke. OK? Now, we talked about mechanism with good bacteria and the things that they're doing for us in the GI tract, then we can talk about the bad microbes.

And I would suspect that these are ones that maybe release a toxin that causes a lot of inflammation and so you have actually a damage of the intestinal wall and so then you get the diarrhea and malabsorption and blood in the stool. Is that a good summary?

Dr. Sandra Kim: Good. I think it is and I think it depends on the type of bacteria. Let's talk about E. coli, E. coli are not all created equally. So there are different types of E. coli that cause disease and symptoms that can vary depending on how it is what we call "virulent". Virulent just means how we can cause its damage.

And so some actually produce what we call toxins or chemicals that cause the damage directly. Other E. coli can affect certain things in sort of how your fluid pumps work what we the AMP pumps, for instance, and have sort of a similar presentation to an infectious diarrhoeal disease called cholera.

Other ones can cause damage by stimulating white blood cells to produce those very inflammatory or more harmful those cytokines that we talked about to then exert damage to the lining of the GI tract. So there are different ways. Another bacteria that we're very familiar with is that C. difficile or C. diff that can produce toxins to also cause damage as one of its main mechanisms.

40:38

Dr. Mike Patrick: So how do we then eliminate the bad microbes? I mean, obviously you think antibiotics could kill the bad ones, but then don't you kill the good ones with it? How do you deal with that?

Dr. Sandra Kim: I think that sort of, again, it's one of these grey zone questions, I think sometimes, again, it's become so much the bad versus the good. If you have an acute infection, specific bacteria associated, for instance, like having strep throat, having a specific type of pneumonia or an ear infection, of course you must use the antibiotics to get rid of the bacteria that we think is causing an infection without question.

The bigger issues though is with the GI tract because a lot of the "bacterial" or even "viral infections" in the intestinal tract, a lot of it is just change over time because we don't treat most bacterial and certainly not viral infections, but even bacterial infections in the GI tract with antibiotics because we know it's often self limited, it runs its course and depending on the types of bacteria it may actually prolong how infectious you or your child may be with it.

So we have to sort of judiciously choose. I think one is treating if it's an infection that must be treated. But I think the bigger way to look at it is knowing that there are certain types of bacteria in reasonable amounts are always going to be a part of your GI tract. The bigger issue is figure out ways to balance things out with more the protective bacteria.

Dr. Mike Patrick: Yeah. So there's a lot of folks who have C. diff living inside their gut and if you did a stool test it's going to be positive but if it's not causing any symptoms or disease you sort of let it be.

Dr. Sandra Kim: Absolutely. And in fact, that's one of the things that antibiotics used judiciously is crucial, what would we do without antibiotics? But at the same time we want to make sure it's very clear what we're treating because what we don't want to do is give an antibiotic unnecessarily, wipe out the good bacteria that are hidden with the "bad bacteria" and then actually cause more problems down the road.

42:41

Dr. Mike Patrick: Sure. What's the use of something like Florastor, which is a yeast type of microorganism, that then I would assume that's not killed by a traditional antibiotic? Is there a use for something like that when kids are being treated with an antibiotic for like let's say an ear infection?

Dr. Sandra Kim: You could but I think this is where it becomes interesting because you have folks who swear by probiotics and it's not just researchers who'll say this is the best strain, whether it's the Florastor with the yeast or Culturelle, which is a strain called lactobacillus GG or even a combination of different types of "probiotic or good bacterial strains" like VSL#3.

I think it's understanding the specific relationships between the different bacteria and I think that's where it becomes difficult. I always say the probiotics typically if you're not immunosuppressed won't hurt, but I wouldn't necessarily be discouraged if let's say giving Florastor, for instance, helps or doesn't help; because it may be that in your child that that may not be the only probiotic that your child needed or was deficient or it may not even be fostering growth well if we don't have something else helping it.

And so that's why I think the sort of the next phase for all of us in the medical community is to have a better understanding of the types of probiotics, the combinations and in what sort of individuals certain combinations would work better or not.

Dr. Mike Patrick: Yeah. And I'll put a link in the Show Notes to a nice article from the American Academy of Pediatrics that talks about prebiotics and probiotics. So folks out there who are interested in sort of some of the research behind it and what the AAP's recommendations are they can find that and we'll put that in the Show Notes.

Dr. Sandra Kim: Absolutely. And I think folks will find this a very lovely compilation of what we called both evidence-based reports versus clinical trials versus smaller studies and overall recommendations, which ones are clinically indicated and which ones require more research. And I think the listeners will find that very helpful.

44:49

Dr. Mike Patrick: Yeah. So you are an inflammatory bowel disease expert and we've kind of skirted the issue of Crohn's and ulcerative colitis here. So let's just lay it out there. What is the relationship between the microbiome and inflammatory bowel disease?

Dr. Sandra Kim: Perfect. And even before we go further, for some of the listeners who may not know what inflammatory bowel diseases are, I think sometimes there's a little bit of confusion, people hear IBS or irritable bowel syndrome, which is a functional type of abdominal pain type of syndromes but no underlying inflammation per se, traditionally, versus inflammatory bowel disease or IBD.

So inflammatory bowel diseases are chronic diseases, so there is no cure unfortunately, yet, although the goal is always to maintain remission with the combination of different types of medications. And so when people hear IBD these are classically known as either Crohn's disease or ulcerative colitis.

So Crohn's disease can affect any part of the GI tract; ulcerative colitis classically in the colon. So what's the relationship between bacteria in IBD it's really what we call multifactoral. So I wish I could show you all a picture, but if you all remember the Venn diagrams from middle school or elementary school, you remember how you have the different circles and they intersect.

So if IBD was the intersecting area, we know it's a combination of bacteria but also environmental factors that may cause issues with the lining of the intestinal tract. Genetic predisposition and I'll talk about that in just an instant and then inflammatory responses or rather the presence of abnormal inflammatory responses to different triggers.

We know that bacteria are crucial and I'll tell you that some of our first studies came from animal models. Remember I talked about these germ-free mice? So there are several models of colitis when they are raised germ-free they do not develop inflammation. When they get specific types of bacteria then they will develop different patterns of inflammation.

In fact, my original research group was one of the major groups that actually published in this. So this tells you that it's not just genes but bacteria. So if you've got the genes with no bacteria you don't develop disease and that happens in humans as well.

47:10

So then let's look at humans. And folks will say to me, so someone has Crohn's disease, my child has Crohn's disease, why are they presenting differently? Or I just want to get that one gene test that tells me whether I'm going to develop it or not.

So folks, there are almost 200 genes associated with Crohn's disease or ulcerative colitis alone. Some of them may just be associations and some of them may actually be causative and that's one of the crucial areas research were looking into.

How are these genes important? Some of these genes are involved in how your body clears bacteria, processes bacteria, how your body response to bacteria. So you can see, I kind of tell folks that when you develop IBD it's sort of like the ultimate dysfunctional relationship. Wrong genes in a person meet the wrong bacteria and the wrong bacterial genes at the wrong time to develop that inflammation. And so that's where they're related.

Dr. Mike Patrick: So it's very complicated.

Dr. Sandra Kim: It is. But you know…

Dr. Mike Patrick: It's a complex interaction.

Dr. Sandra Kim: It's a complex interaction but remembering it's about genes, bacteria and the environment leading to an abnormal inflammatory response in a nutshell.

Dr. Mike Patrick: Sure. And folks who are interested in knowing lots more about IBD, Crohn's and ulcerative colitis, we did do a PediaCast specifically on that topic where we really went into detail on the mechanisms and how it presents, how it's treated, long-term outlooks, all that kind of thing.

I apologize I don't remember the episode number on the top of my head but I will find it and we'll put it in the Show Notes. So anyone who's interested in knowing more about IBD itself just head over to pediacast.org, look under the Show Notes for episode 243, which is this one and there'll be a link to our IBD episode for you so you can hear all about that.

49:04

Dr. Sandra Kim: Right. My wonderful colleague, Dr. Wallace Crandall, MD, who's the overall director of our IBD Center, did a lovely job with that, so I think folks will really enjoy that.

Dr. Mike Patrick: Yeah. Absolutely. It was really very clear and it was an enjoyable interview. Now what about other chronic diseases outside of the intestinal tract? For one, obesity for instance. Is there a role, and I consider obesity a chronic disease, is there a role of which gut bacteria we have in obesity?

Dr. Sandra Kim: Absolutely. So again, take home message is not it's just the bacteria's fault as much as we'd like to blame the bacteria and it's not just about giving the right or wrong combination of probiotics. But again, same group that looked at the human microbiome looked at developing the tools that we need to study this, looked at twins initially, obese versus lean and saw that there were distinct differences in the microbiota.

It wasn't one bacteria. And I have families who say, so what bacteria do I need to take? I'm like no, it has to do with proportions. Again, remember the colon is a social organism so it's about relative proportions and levels of different groups of bacteria and found that there were differences.

So why does that happen? One may actually be diet, itself. Remember we talked about how the diet affects the proportions of bacteria. So yes, diet still matters. But the other issue may be that in folks who are predisposed to being more overweight or obese that the bacteria that sort of predominate in their intestinal tracts are often very efficient scavengers of energy.

And so because of that your bodies become really efficient where we like efficiency in a lot of things but not so much when it comes necessarily to caloric issues. But that's like a really unique westernized phenomena, because I want to bring up something that we often forget here in North America and that is the opposite problem that our colleagues in developing nations have were that with severe malnutrition.

And again, a beautiful study that recently came out in the New England Journal of Medicine looked at giving selective antibiotic therapies to children who had severe malnutrition and had sort of what we call a neuropathy or changes in the intestinal tract and the associated things like diarrhea and weight loss; and found that selective antibiotic usage could actually help save many of these children.

So whether it's overly efficient or not efficient enough, the bottom line is we know that the bacteria are important in terms of nutrient metabolism. Another thing, I think, we talked about diseases is atopic diseases. Atopy means things like allergies, asthma, eczema or what we call atopic dermatitis.

And so there have been different studies that looked at whether for instance giving mothers probiotics before the kids are born or while they're breastfeeding may help prevent these children from developing these atopic diseases, the verdict is still out.

Then the second sort of level is taking kids and adults who already have these atopic or allergic type of diseases giving them probiotics and again, some find they may help, some say no, but this again is an avenue of research that I think we really have a strong interest. So I think those are some areas that are outside of the GI tract that we can think of.

52:34

Dr. Mike Patrick: Yeah. There is one study to look at babies with colic and probiotics.

Dr. Sandra Kim: Yes. Absolutely. And what they found is that from the sample size or number of infants looked at that you could not definitively say that giving probiotics would help resolve colic. And in fact, if you go to that pediatric position paper that Dr. Mike was talking about, there is a very nice sort of two-paragraph summary.

But again, I think clearly we know that there probably is a role and this is where it becomes very important, not just to ultimately say that probiotics have failed but rather say so let's be smarter about understanding what the probiotics do, the mechanisms of how they may act, what sort of groups of kids and adults we need to look at and target better.

And that's one of the areas that the scientific community is looking at. Not just to understanding sort of what we call associations, but actually trying to figure out causes and what we call mechanisms or how something actually happens and not just an association.

Dr. Mike Patrick: Yeah. And sometimes when you look at it from a symptom standpoint there may be multiple mechanisms in different people that result in the same symptoms, which can make ti more difficult. And I only bring that up because we talked about colic before on here and said well, it's probably a neurological issue that the cry center of the brain is just firing, but not all colic necessarily is the same flavor and so that's why maybe sometimes probiotics would work and sometimes they wouldn't.

Dr. Sandra Kim: Absolutely. And again, what we are calling even colic, is it actually something else more GI tract-related? Is it true colic where we think it's more neurologically based or is there also a component, for instance, of some GI issues whether it's been changes in how the baby has a bowel movement, how they're processing the formula…

Dr. Mike Patrick: Like acid reflux or whatever.

Dr. Sandra Kim: Right. Acid reflux. Absolutely. So I think there are different things that may be contributing.

54:33

Dr. Mike Patrick: Yeah. What about type 1 diabetes?

Dr. Sandra Kim: So again, with the autoimmune diseases this all ties in to some of the research not just type 1 diabetes but what we call metabolic syndrome, which is a little bit different. This is more insulin resistance, which is different from type 1 diabetes which is insulin dependence and looking at all the other factors.

And clearly, there is a feeling that there are changes in your GI tract microbiome. And the problem, though again, is it causative or is it a result of the changes metabolically. And then we talked about sort of autoimmune inflammatory diseases or disorders knowing that obviously metabolic syndrome, which is more insulin resistance, is different from type 1 diabetes, which is more autoimmune sort of a mediated.

So is there a sort of an infectious or microbial trigger based sort of phenomena that causes sort of the inflammation that you get that leads to it.

Dr. Mike Patrick: Yeah.

Dr. Sandra Kim: So I think it is both cause and effect.

Dr. Mike Patrick: Yeah. We've talked about some of the hot topics really in microbiology research as relates to the gut. So we talked about identifying these organisms, finding out what the right mixes are, what are the viral bacterial interactions that might take place. If there's a young person interested in microbiology research, we're really just ready, kind of at the beginning of a whole new era of figuring stuff out.

Dr. Sandra Kim: Absolutely. And I think, again, when I talked about the Human Microbiome Project I don't think I told you how passionate all of us in the medical and microbiology field (call me a micro geek) are. So folks may be familiar with the Human Genome Project, which was a phenomenal undertaking led by Francis Collins at the NIH to really gene map out genes associated with a lot of our known diseases.

Well that's what the Human Microbiome Project set out to do back in the late 2000s, back in 2007, to map out the basics sort of microbial genes and microbial populations in the human, the genome. And really, again, the power…

Dr. Mike Patrick: Or in the bacteria…

Dr. Sandra Kim: In the bacteria. Yeah. The microbiome, the bacteria. And so again, I think it's taking the current tools but continuing to expand them further so we can better define the current microbiome, which doesn't just focus on bacteria but understanding better the relationship with things like fungi and viruses.

I think then taking this knowledge and right now we've talked about a lot of potential relationships, but as a clinician and as a researcher we need to not only take what we have been able to see and define but then to take that one step further and understand the mechanisms of how the microbiome affects healthy individuals first. Because if we can't understand healthy individuals then we can't go to diseases. But then going to diseases so that we can better understand mechanisms and better target therapies.

Diet becomes huge and I think as you know, Dr. Mike, there's been more and more on the role of diet, specific foods, specific types of foods and how we can alter the bacterial composition, but not only alter it short-term but try to make more life-long changes.

And then I think new things are the effective use of probiotics and coming up with more targeted types of probiotics. And we didn't even touch on fecal transplantation, so it's basically giving someone stool. And in fact, there have been recent studies that actually looked at using fecal transplantation, taking stool from a healthy individual and giving it to someone who has disease.

And so the recent studies looked at C. diff or C. difficile colitis and found that in individuals who were resistant to antibiotic treatment giving the fecal transplantation, so to speak, helped when given from a healthy individual.

58:52

Dr. Mike Patrick: There are moms and dads shaking their head right now.

Dr. Sandra Kim: I know they're shaking their heads but at the same time parents will say, listen, you know what if it doesn't have toxic side effects, it works we'll go with it.

Dr. Mike Patrick: If it works. Yeah. Yeah.

Dr. Sandra Kim: But people are going to hear more and more about fecal transplantation as a way of dealing with infectious colitis, but other potential autoimmune inflammatory type of diseases; some more to be published and talked about in the future.

Dr. Mike Patrick: Yeah. Yeah. Absolutely. Well, we appreciate you stopping by. I always do this. I had every intention of this be in about 30 to 40 minutes and it's been an hour.

Dr. Sandra Kim: Oh, well.

Dr. Mike Patrick: No. No. It's fine. It just you know, I get chatty and that happens. But we had some great information today and just really appreciate you stopping by. So Dr. Sandra Kim, pediatric gastroenterologist here at Nationwide Children's Hospital, thanks.

Dr. Sandra Kim: Thank you so much!

Dr. Mike Patrick: We're going to take a quick break and I'll be back with a final word, right after this.

[Music]

01:00:21

All right. We are back and my final word this week is a little self-promotion for our hospital. Nationwide Children's was recently named one of the 10 Best Children's Hospitals by Parents magazine. Specifically we are recognized for world-class service in emergency medicine and trauma services, pulmonary, hematology, oncology, neonatology and pediatric cardiology.

So congrats to the fine folks here in Columbus and thanks to Parents magazine for recognizing our sometimes difficult but often rewarding work and that is my final word.

One more time, I want to remind you the 2013 Pediatrics Pearls Conference for clinicians, Thursday, March 28th 2013 from 7:30 in the morning until noon on the campus of Nationwide Children's Hospital. And again, there'll be a registration link in the Show Notes over at pediacast.org for episode 243, which is this one.

I want to thank all you for taking time out of your day to listen to the program and being part of our audience. I also want to thank again, Dr. Sandra Kim, the Medical Director of our Inflammatory Bowel Disease Center at Nationwide Children's Hospital.

Also I want to remind that we are on Facebook, we're on Google +, Twitter and Pinterest so you can share our stuff there. And be sure to tell your family, friends, neighbors and coworkers about the program. Most importantly, tell your child's doctor. So next time you're in for a well check-up or a sick office visit just let your primary care pediatrician know about PediaCast.

And we do have posters available under the Resources tab at pediacast.org that they can hang-up in their office or in exam rooms. And when you tell them about the show, again, just the keyword is evidence-based and for parents.

I want to remind you if you'd like to contribute to the program, if you have a question for me, you want to suggest a show topic or point me in the direction of a news story or if you just want to say hi, head over to pediacast.org, click on the Contact link and you can get a hold of me through that mechanism.

All right. It is time to go and until next time, this is Dr. Mike saying stay safe, stay healthy and stay involved with your kids. So long everybody!

[Music]

Announcer 2: This program is a production of Nationwide Children's. Thanks for listening. We'll see you next time on PediaCast.

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