Science continues to unravel the mysteries of the microbiome and its deep connection with our overall wellbeing.
Today we are joined by Dr Johan Van Den Bogaerde, a gastroenterologist and researcher who has a special interest in the microbiome and the emerging field of faecal microbial transplants. Dr Van Den Bogaerde shares with us the current scientific opinion on the influencers of gut microbial diversity and he shares his excitement about the research expanding the potential treatment avenues for faecal microbial transplants in areas such as ulcerative colitis and autism.
Dr Van Den Bogaerde will be a key note speaker at the forthcoming ATMS GI Symposium in Sydney in September 2019.
Covered in this episode
[00:51] Introducing Dr Johan Van Den Bogaerde
[01:56] Gut diversity: still so much learning to be done
[15:32] The influencers of microbiome diversity
[21:25] FODMAP diets and microbial diversity
[24:54] Small intestinal bowel overgrowth; SIBO
[32:04] Bowel motility
[34:21] Stress: cause, or effect?
[36:47] Autism and the microbiome
[42:37] Into the future: faecal microbial transplants
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook. Joining us on the line today is Dr. Johan Van Den Bogaerde. He completed his undergraduate training in South Africa with postgraduate training in the United Kingdom at Cambridge, St. Marks, and Hammersmith Hospitals. In 1998, he was appointed professor and seconded to St. Mark's Hospital, where he held joint positions in the Department of Physiology, and as a consultant in the Department of Gastroenterology and Internal Medicine. He's held positions as conjoint senior lecturer and conjoint associate professor with the University of New South Wales and still maintains links with his local University of the Sunshine Coast, Queensland.
Dr. Van Den Bogaerde believes gastroenterology is an exciting and important field and has very broad interests, including the study of the microbiome, oesophageal pathology, motility disturbances, inflammatory bowel disease, and functional bowel disease. Welcome to FX Medicine Johan, how are you?
Johan: Thank you very much. Excellent, nice to hear you.
Johan: It's extraordinary what is going on in the gut and the extraordinary new stuff coming out is absolutely amazing. They've very recently described a new complete branch of organisms in the gut, called the ‘CPR branch.’ Now, to think about a branch of animals, it's really important that the one branch is the eukaryotic branch, which includes plants, animals, all multi-cellular organisms. Then you get bacteria as a second branch. And then you get archaea or archaic type of bacteria as a third branch. And now the fourth branch is the CPR branch, which is a completely different type of bacterial structure.
It's a tiny bacterium, and it represents 30% to 40% of bacterial diversity. And we've only recently discovered this and discovered that this is actually present in the gut.
The exploration of unique organisms in the gut is taking off, and we're discovering new things every day. If you look at the microbiome literature there's more than 17,000 publications at the moment and growing as you say, every day.
The microbiome is not simply the gut. It includes seven different types of microbiomes, including the lung, the skin, the oral, the vaginal, the penile. The skin microbiome, for instance, contains 10 million organisms per centimetre of skin. So we are in fact, host to very common organisms that we've known about for a long time. But we're also host to viruses, fungi, and organisms, which are completely unknown to science and are only now being discovered.
Andrew: I have to ask a question about this CPR branch. Does this include the segmented Filamentous bacteria? It's been something that I harp on about in many podcasts, and they interest me acutely, but they're really hard to culture.
Johan: All these things are quite difficult to culture. The reason microbiome research has become a big thing in the last 10 to 20 years, is because traditionally microbiologists culture organisms and look at them on plates. But although these are very robust organisms, they're extremely difficult to culture.
So when you look through the lens of microbial culture, you see only a fraction of the organisms that are available, or that are there. The way that we really look at them now is to look at their genetics and sequence them and do metagenomic analyses, which then give us the whole picture of exactly what is there.
We have learned to culture some of these organisms, but culturing 99%, in the conventional way, is impossible. So every bacterial culture we do looks specifically at organisms we can culture, but they represent a small fraction of what's actually going on there. And in particular, these new forms the archaeas, and the CPR branch of organisms, which seem to be very important in disease.
Andrew: Every day, there is a new discovery in our microbiota/ microbiome, which we need to take heed of. I think it poignantly shows us just how little we know about our gut. But let's delve a little bit into, at least something that we know of, and that's, you know, the rest of the microbiota, not just the bacteria, but the fungi, the bacteriophages, and viruses. Can you tell us a little bit about how much they comprise, what do we know, and what don't we know?
Johan: So, when you look at the organisms in a typical human gut, we know that our bodies have 30 trillion cells. And there's approximately 39 trillion, let's say ‘other cells’ in our gut. So, the bacteria and the organisms in the gut outnumber our body cells, and certainly, their genes outnumber our body cells by 100 to 1 at least, because each of these has a different genetic component.
Viruses and phages are filled in the gut and funguses are also all over in the gut. We have no real idea how these work. We know that some bacteria control fungi, so for instance some of your bacteria will produce products that suppress fungal growth. But we also know very well, that fungi suppress bacterial growth, and that's the basis of antibiotics. So how these organisms interact is very, very difficult. At this stage, we really only know phenomenology. We Know that they are there, we can pick them up, and we can say something about their distribution. We can say very little bit about their function.
We do do metabolomics where we look at genes expressing functions. So we know that... you know, for instance if there is a gene, making a short chain fatty acid, we can pick that up genetically in the bacteria. We can't do any of that, for the viruses and the fungus. And the phages are a completely different group of organisms, which make it even more complicated. They sort of parasitize viruses, I mean, viruses eating viruses. It's you know, bacteria, and funguses controlling each other in different ways. And all living together in the gut. And more importantly, living in different parts of the gut. So your microbiome differs dramatically in your oral cavity, to your stomach, to your small bowel, and then in your colon where the highest concentration of microbiota are found.
But there's different gradations of importance microbiota. So, a bacterium or a fungus in the lumen of the gut is perhaps less important than a bacteria or a fungus right on the wall of the gut. So you get your population, which is right next to the mucosa and the mucosal cells and it's very intimately associated with the immune cells of the gut. We know that the gut has more immune cells by far than any other organ in the body.
So you've got a very close interaction between organisms that are micrometres away from macrophages and antigen-presenting cells within the gut lining. And if you reduce that gut lining, then these organisms get closer and become more dangerous. And if they penetrate the gut, then obviously different things happen. And that's the pathology of many of these diseases. Inflammatory bowel disease, for instance, one of the important pathologies is that you get bacterial translocation. Also in patients with hepatic problems, it looks like bacterial translocation going through the gut lining. So the organisms within the gut lining are also a completely different population. And perhaps more important than the population in the lumen.
Johan: Yes, yes.
Andrew: And that's helicobacter pylori. Do you see a common culprit or culprits with regards to inflammatory bowel diseases, specifically Crohn's?
Johan: No, I definitely don't. And when I did some research at St. Marks and then Professor Kamm who was running the research there, he sort of felt that we have to look for this sort of organism. And the same as with Coeliac disease. There's a specific protein, a specific key that unlocks the coeliac disease. That’s gluten protein. And with helicobacter, for instance, there’s a specific organism which unblocked peptic ulcer disease. So we have thought about is there a specific organism, is a specific food type, is there a specific antigen? The first step to Crohn's disease and all the other things develop from it.
But I didn't think there'll be one specific organism. I think it's an extremely complex disease, which is associated with genetics, with immunology, with food, with bacteria. But certainly, the microbiome is, I think, becoming the more important factor in pushing and driving the immunology of this disease. But to find one organism, absolutely, I would be very surprised.
There are organisms that are protective, the prausnitzii group of organisms that produce anti-inflammatory substances and actually run via the NF-Kappa system. Now the NF-Kappa system is the sort of key molecule in inflammation and reducing inflammation. And we know that these organisms increase interleukin 10, which also reduces inflammation. So certainly organisms that can break through the immune system and stimulate immunity, but then also organisms that reduce immunity and work as a natural sort of steroids, if you would.
But the complexity of what's going on there is, phenomenal. And we're only just beginning to understand what bacteria are there. We've got no idea what role viruses like archaea and all these other funny organisms play.
Andrew: Martin Blaser has written a book called Missing Microbes some years ago now and of course, he questions not that helicobacter is implicated in peptic ulcer disease. But what he talks about is the different strains. And you know, we're well versed about the strain specificity, denoting the actions of a bacteria, let's concentrate on the bacteria at the moment.
Andrew: And that one, lactobacillus acidophilus ‘code’ is not the same as another lactobacillus acidophilus ‘code’. Similarly, helicobacter that there's a lot determined by the genes, I think there's the vacA?
Andrew: Yeah. So are we blaming a whole organism for something that's strain-specific, and should we be identifying the strains to see if that's the bugs that we should be eradicating?
Johan: I think that's a very good point. I don't think we've... I mean, there's different species of helicobacter as we know. And you can get cag type helicobacter and helicobacter heilmannii in humans. But you'd certainly do get different strains that have got a different virulence and we've known that since the beginning of time, as far as microbiology is concerned.
I do you think we have the tools now to look at the more dangerous types of strains and then... but I don't think we really are at a phase where we can target our therapy for these different strains.
Johan: I mean, if you've got... It may help us to, determine the aggression of our treatment. So if you look at helicobacter pylori, for instance, certain of the strains, and that's been well defined, as you point out with the vag, is that some of these are dangerous and others aren't. And we know that most people have helicobacter and they never have a problem with helicobacter. And there was a fascinating theory advanced by some African or South African gastroenterologist that it is, in fact, protective. Because they looked at the African population where 95%...
Andrew: That's right.
Johan: ...of the population had helicobacter and almost none of them had gastric cancer or ulcers. So then they sort of provocatively said that maybe it protects against ulcers and cancer.
But certainly, one helicobacter is not equivalent to another helicobacter. And certainly, one faecalibacterium prausnitzii is, not the same as another faecalibacterium.
Johan: And definitely, one clostridium is different to another clostridium, as we know.
Andrew: Yes, absolutely.
Johan: But how we're sub-typing the many thousands of different species and then looking at how they exactly cause dangerous problems and toxins, and how you would differentially treat them is going to be I think not super productive.
I think if you do find certain organisms like clostridium difficile, you will try and eradicate it without really being cognisant of exactly how dangerous the strain is.
Andrew: Yes. Maybe a question between dangerous or catastrophic for the patient, yeah.
So let's talk a little bit about gut microbial development. You know, we used to think that the baby was sterile, in-utero and that the majority...or no, the totality of the baby's microbiome, developed from the vagina of the mother. But then there was recent evidence, I think, University of Madrid? Showing this entero-mammary pathway, that the breastfeeding was actually very important in translocation, that there was active transport by monocytes of bacteria from the mother's gut through the lymph, through the breast milk into the baby. So what's the understanding now of the development of the microbiome?
Johan: I think the understanding is that I think in-utero, we're mainly like germ free animals. And then the minute the baby comes out, it's exposed to this universe of microbial, just extraordinary diversity. And we know, for instance, that breastfeeding changes the baby's microbiome, vaginal delivery changes the microbiome, home birth changes the microbiome, caesarean section has a profound effect on the microbiome.
But I don't think we should over interpret these data. Because I think, basically, your microbiome, by about the age two or three seems to be fairly stable, and it seems to be very similar to the siblings and the people that you grow up with.
So what initiates the microbiome clearly is your first contact as you come out of the uterus. Whether that is in a hospital environment, or in a tiny house in a rural community will obviously change it. If one has to choose, let's say a better microbial signature, it would probably be to be born in the...perhaps having a home birth in a rural African community, those are the best microbiomes one can have.
The worst microbiome you can be born with, I would imagine would be a caesarean section microbiome where you get born into a sterile theatre, with very little variability of organisms. But that sort of evens out with diet when you get whole food, when you get weaned off the breast. And I'm not sure that is fantastically important in the bigger picture. I think it is important exactly when babies are weaned, I think it's very important what diet they get. And I think the most important perhaps, is, in what sort of sterile environment babies get raised. We know that the more sterile your environment is, probably the higher chances of getting inflammatory bowel disease.
Johan: There's been long term data emerging that the further north you go from the equator, the higher your incidence of inflammatory bowel disease is, in particular, Crohn's disease. And it may be that it is simply a side effect of if you live in an equatorial, more developing country with a rural sort of diet, you get a fantastic microbiome. If you eat African type food, you get a great microbiome.
The worst sort of food you can eat is the western-type, refined food. And the worst lifestyle you can have is the western-type, sterile-type lifestyle where you don't as a baby get involved in the dirt and the chickens, and the goats, and things like that.
So I think that's an important thing to think about. I think one has to have a varied microbiome. And that's achieved by eating a sort of a diet rich in fibre and rich and in sort of natural-type foods.
Johan: There's been a very interesting study done with African Americans and African Africans. And the study looked specifically at cancer. And we know that African Americans have a very high incidence of cancer. And that's been related, the whole cancer thinking in bowel cancer has somewhat changed that it could start with inflammation. And that the inflammation could be initiated by an abnormal microbiome.
And the African Americans have quite a poor microbiome, they seem fairly dysbiotic. Whereas the African Africans have a fantastic microbiome. Different Africans living in different places, obviously.
Johan: If you live in a deeply urbanised environment, like Johannesburg, you'd have a very different microbiome to someone living in Tanzania, living sort of a hunter-gatherer lifestyle or living on a small farm in Tanzania.
But if you then change... if the African Americans change their diets to the African-African type of diet, which is high in fibre, low in western sort of processed foods, they can within two weeks change their microbiome into really quite a good microbiome.
So microbiome changes with diet, and with exposure to things in your environment, it happens quite quickly, and it can be profound. And the other side of the coin is the African Africans when they ate McDonald's and drank coke…
Johan: Their microbiome became horrible. So I think that's interesting. So having a microbiome it's not a life sentence, you can change your microbiome. So a baby born by caesarean section with perhaps quite limited microbiome can, as a child, get a very good microbiome.
Andrew: Just to follow on from something you said there about latitude, I mean, that smacks very similarly of the world map of multiple sclerosis. But then, of course, humans are so good at looking at one thing or trying to find the one thing that's the culprit. One would immediately think about vitamin D. But it's so much more than that. You just mentioned socioeconomics, there is a very important part of the difference between African Africans and African Americans.
Andrew: And of course, there's that really good research from Jeff Leach that showed that you can change your Western microbiome back to a very diverse set of organisms by eating the sort of hunter-gatherer lifestyle, and we know about plant-based diets as well. So I guess the problem is, how, as a clinician, do you sift through all of the data, and then help a patient you know, with a problem with dysbiosis, which we'll get onto later?
Johan: I think it's extraordinarily difficult. And I'll give you an example. There was a recent discussion actually in an anaesthetic conference and I looked at some of the interesting lectures there. And there was a fascinating lecture about microbiome and functional bowel disease...irritable bowel. And they looked at the FODMAP diet…
Johan: Which symptomatically we know… So the FODMAP diet is a diet low in sugars. And we know that sugars generate gas in a bowel particularly in certain patients and the enemy of anyone with irritable bowel is gas. Because they've got what we call visceral hypersensitivity, so their bowels are more sensitive to distention than someone without functional bowel disease.
If you give people a good FODMAP diet, and there's excellent data for this, you'll see that their symptoms definitely get better. They become less bloated, they've got less pain, they just do much better. But if you look at their microbiome, the FODMAP diet, in fact, makes the microbiome less diverse. And in particular, it reduces the number of Firmicutes which are ‘the good guys,’ you get good guys and bad guys in the microbiome.
So, you know, good organisms are things like Firmicutes and bifidobacteria. The bad organisms are, for instance clostridium difficile, which causes an inflammation and antibiotic-associated colitis. So a good microbiome is one with lots of these good guys, and the bad microbiome, are the ones with bad guys. And a good microbiome has got high diversity and a bad microbiome has got less diversity.
When you get born, you've got virtually no diversity, you develop diversity as you get older, and then when you get really old, you get very little diversity as well. So your diversity goes down as you become very old. So you've got to hit the sweet spot of microbial diversity, which you can achieve by diet. But by following an absolutely accepted diet, which we know works in irritable bowel syndrome, we reduce our diversity and more importantly, we reduce the good guys. So how you marry those two together is actually very difficult.
Andrew: Does that form along the lines of the theories of SIBO, which is the small intestinal bacterial overgrowth that we're actually kind of like, ‘giving the bowel a rest’? Similarly to what happens sometimes with Crohn's treatments where sort of, let's say oligoantigenic diet is given for a while just to rest the bowel?
Johan: Yes. So that question you've asked is actually quite an exciting question. And whenever patients say to me, "Tell me about the microbiome," I say to them, have you got four hours? So that question is a four-hour answer, but I'll, obviously reduce that to…
Andrew: I'm up for it.
Johan: And we'll have all our listeners passing out and yawning I think at this. So let's focus a little bit on SIBO, small intestinal bacterial overgrowth. I think it's something...and I was in a lecture three days ago with an absolute expert, a colleague of mine called Jack Begler [*ed] who's a fantastic researcher and a really clear thinker. And there are bacteria in the small bowel. They're much less in the small bowel than in the large bowel. And he said, well, he's not so sure about SIBO and how easy it is to measure it and to treat it.
In essence, SIBO I think is when you get poor motility or something that affects the motility of the upper small bowel, you get bacterial overgrowth. And that bacterial overgrowth causes fermentation in the small bowel. Normally, fermentation is limited to the large bowel because you've got a high bacterial density in the large bowel. And if you feed the large bowel bacteria, sugars that haven't been absorbed, such as inulin that will then allow them like yeast in a bread that's rising to make gas and grow. And the theory is that the same thing happens in the small bowel.
I think it's something that we've been over-calling lately. I think you do get patients with abnormal populations in the small bowel. But I think it's less common, and I think it's quite difficult to document and quite difficult to treat.
What we do sometimes find is if you get patients with blind loops, I have recently seen a patient with a large diverticulum in the small bowel and clearly…
Johan: You know, we know in the diverticulum...
Andrew: In the small bowel?
Johan: Yes, so it is sometimes seen.
Johan: So, this patient had prominent diverticular disease in the small bowel.
Johan: And in this very large diverticular pouch, obviously food stuffs gets stuck and then you get problems there, and you get bacteria growing there. And that to me...so if you get a sort of a poorly emptying bag of bowel then you can definitely get overgrowth there. Either with motility disturbance or some surgical problem in the bowel where you got a blind loop. And then certainly that can cause massive bacterial growth in the small bowel. And that would be small intestinal bacterial overgrowth.
But it's been a little bit over diagnosed I think and over emphasised. It has always been difficult to know what is colonic pain, what is small bowel pain? How does functional bowel disease work? It's a very complex issue.
There was a very interesting picture a little while ago, a video of a nurse at one of the conferences, who was very much into diet and probiotics. And she took industrial doses of probiotics and they showed a picture of this patient taking 16 or 17 probiotics three or four times a day. And the probiotics...they were so… she flooded her proximal bowel with so many probiotics that in fact these probiotics like yeast in a bread just basically exploded in her gut and caused immediate and pretty dramatic small bowel distention which you can actually see.
So you definitely can change your gut microbiota. You can give the small bowel too much to work with, and you can give the colon too much to work with, which leads to fermentation. But yes, small intestinal bacterial overgrowth can be treated as an entity, but I think it's probably been a little bit over-diagnosed. And I think it is difficult to diagnose because your small bowel has got quite a lot of bacteria anyway.
Andrew: And of course, how do we test? What exactly are we testing when we think we're testing, you know?
Johan: Yes, exactly.
Andrew: One of my challenges has always been when we're doing a faecal test, well we're testing what's in the faeces, not what's in the gut necessarily nor where in the gut.
Johan: Exactly. So you wouldn't be testing what's in the small bowel. The way we look at SIBO is to give patients stuff that then we then measure the breath excretion. So if the bacteria are being active in the small bowel, they produce gases which we breathe out. And then you can see that the methane or something that we breathe out comes more quickly.
So let's say you give someone a lactulose feed then, or some sort of sugar that you give, then you'll see that the breath excretion is much quicker if it's in a small bowel than if it's in the large bowel. And that tells us that there's fermentation activity in the small bowel. Which would be abnormal. So it is an entity, we can measure it. But it's not easy to document nor to treat really.
Andrew: If part of the issue of SIBO is that it's the bacteria that normally inhabit the colon growing in the small intestine and we're doing a breath test for something that we're breathing out through our lungs, how do we know that the fermentation has got to do with the bacteria overgrowing in the small intestine, rather than say, the proximal colon? How do we know that it's happening at that point?
Johan: Well we don't. But we sort of think that if it happens quickly, because the fermentable substance has to go through the small bowel first. So let's say you get something within 30 or 40 minutes, then it's probably the small bowel, whereas if you get it within an hour or so it's probably not the small bowel.
Johan: So it's just a time-based thing.
Andrew: So it's got to do with motility.
Johan: It's got to do with motility and it's very rough.
Andrew: Yeah, because then one of the issues with SIBO is motility.
Johan: Yes, exactly.
Johan: I think that's the main issue with SIBO.
Johan: Is reduced motility which allows overgrowth. Wherever you get any body cavity that doesn't empty, if your bladder doesn't empty, you'll get an infection in your bladder. If your lungs don't empty, like in a disease called bronchiectasis...
Andrew: Consolidation, yeah.
Johan: ...you will get infection. So we have to flush things out. If your gut doesn't empty, you'll get abnormal infection in your gut.
Andrew: When we're talking about motility, we're talking about knocking out the migrating motor complex. I've heard that that's got to do with majorly an infection by campylobacter. Is that the current thinking of what happens?
Johan: I'm not sure if we really understand how that works. I think gut motility is extremely complex. I wouldn't say that would be my candidate for disordered motility. Certainly not in most functional bowel diseases.
We know that a lot of functional bowel diseases related to enteric infection and certainly campylobacter, which I think is an important enteric infection. Post campylobacter infection, functional bowel disease is a real entity and we do see it. And it can last seven to eight years. And we know that there was this infection of campylobacter in Canada in a place called Walpole, I think? Where they had a fourfold increase of irritable bowel disease up to eight years afterwards. So yes, campylobacter is, I think, very important.
But that motility is also an extremely difficult and variable thing. I'll give you an example of how gut motility and visceral hyperalgesia works. So Professor Kamm did a study many years ago, where he had...we looked at the gut motility of constipation-predominant functional bowel disease patients, and we saw that they've got very disordered gut motility. To measure gut motility in its entirety is actually very difficult. But then we got... I didn't do the study, he did the study. Then he got students to volunteer to not pass stool or wind. And within three days, the students that had withheld the urge to pass wind or stool had identical type of slowdown in gut motility as people with severe constipation and functional bowel disease.
So it's something that changes very quickly. And many patients will tell you that. They say when they go on a cruise, and they change their diet or when they're on holiday with strange people and have got to share toilets, then their gut function and the motility changes completely. So we know it's incredibly variable and can change very quickly.
Andrew: What about with regards to personal stress or perception of stress? I mean, we're talking about hypersensitivity and hyperalgesia, these are pointedly associated with how one feels. You know, do you tend to see, I mean, I'm going to be pigeonholing people, but, you know, personality types, who are more susceptible to SIBO, to IBS, to the functional GI disorders?
Johan: Well, there's absolutely no doubt. So there's an interesting... there's a brain-gut axis and a gut-brain axis. And what I think is going on here is very, very interesting. And if I may, I'm going to speak a little bit about that.
But I once had a long discussion with a very good friend of mine, Professor Sorrentino, about Crohn's disease, and personality types and depression. And there's good data showing that when you fix the patient's Crohn's disease, their depression gets better. So is it true that if you are burdened by a disease, which really affects your quality of life… Irritable bowel disease is a real disease, it's an awful disease. It makes people very, very uncomfortable. And it's a disease that causes genuine pain.
For instance, if you... One of the old tests we did for irritable bowel was to pump air into the patient/ person's guts. So a very simple test, you take a sort of a bicycle pump and pump air up the bottom. A normal patient without irritable bowel can take, let's say, 400, 500 mls. A patient with irritable bowel very soon, after just 100 mls or 200 mls, they become very sensitive and experience extreme pain.
So if you've got a condition, which everyone tells you, is not treatable, which you've never managed to treat despite medication that you take, despite everything you do, you still got this problem that's getting worse that affects your lifestyle, that makes you not able to work, go to school, then it will obviously cause stress. So does stress come first, does stress come second? I don't know. But I do know that having irritable bowel disease is a deeply stressful event. And I'm absolutely sure that it makes it worse. There's no doubt about that. And some by being good treatments, look at reducing stress and doing those sorts of things. And Professor Kamm focuses a lot on that. I think it is extremely important.
Andrew: Johan, you'll be speaking at the ATMS Symposium on functional GI disorders on September the 15th, 2019, which I will urge all of our Australian, indeed overseas if you can get there, listeners to attend that because it's going to be riveting. You know, I've got 20 more questions that I wanted to ask you, but we haven't got time. But firstly, I'd love to get you back on FX Medicine at some later stage, would you be willing to do that and we'll more cover more?
Johan: Absolutely. I would love it.
Johan: Before we go can I just quickly say something, about autism.
Andrew: We're not going yet.
Johan: It feeds into this brain-gut axis. So we know that the brain talks to the gut, but we also know the gut talks to the brain. And we know it does it through substances that are made by the microbiome. And we know that it's via the vagus nerve. So the vagus nerve in a sort of a reverse communication speaks to the brain.
Johan: And there's been some extraordinary new data that's come up published in scientific reports themselves, which is genuinely powerful data looking at autism. Now, if you look at autism as a disease, it shows us how badly the medical profession has treated patients.
So one of the pioneers of autism, Hans Asperger who obviously was one of the first people. But there was a man called Leo Kanner who blamed mothers for autism. I don't know if you've read that sort of literature. And he blamed maternal neglect as a cause of autism. And can you imagine the awfulness of having a child that's deeply impaired and...
Andrew: And then being blamed for it.
Johan: ...some Professor telling you that it's your fault, because you're not a good mother?
Johan: Which led to extraordinary treatments and women and men with children, basically destroying their lives and certainly affecting the lives of the other siblings.
Then, at some point, he realised he was wrong. And then he held a press conference saying, "I absolve all you mothers." I mean, the most extraordinary thing to say after basically making a dreadful mistake.
But now… Then we've had these latest measles thing with autism, which is a completely different issue, and very worrying. But it does seem to be that autism is related to the microbiome. And, have you come across any of that data?
Andrew: Yeah, I mean, the burgeoning data, but still early days.
Johan: Well, yes, but it's extraordinary data. So, in essence, a group in the USA have looked at autistic children, and they took 18 or 16 autistic children and saw that these children had no prevotella organisms in their gut. And had a very dysbiotic microbiome. So dysbiosis being a not good microbiome. They then use faecal transplantation and oral-faecal sort of, intake, to reconstitute the bowels of these children. And they found extraordinary results, six or seven of these children completely recovered. Whereas eight of the children out of the 16 had severe autism that went down to three.
Johan: And a whole group of these kids became completely non-autistic, which is really powerful data.
But the even more interesting aspects of that data... And we see this all over the microbiome. Is that they took the stool of the autistic patients, and gave that to mice. And saw that the mice that received autistic patient's stool became autistic. It's difficult to measure autism in mice, obviously, but there's certain things that mice do that are very abnormal neurologically. And that you could, transfer autism, to a mouse by transferring the autistic stool.
Johan: And this is something that we see all over the microbiome that you can transfer diseases by transferring stool between a patient and a control, to a mouse. For instance, when you look at fatty liver disease, when you look at alcoholic type of hepatitis, if you take the stool of a patient with alcoholic hepatitis, and you give it to a mouse, then that mouse develops the same sort of hepatitis problem. If you feed the mouse alcohol...if you take... Some patients take in a lot of alcohol, but don't develop alcoholic hepatitis, they have a completely different microbiome. So the microbiome is driving the alcoholic hepatitis. And the microbiome can transfer the alcoholic type of hepatitis phenotype to a different species. And this happens reliably. It's extraordinary data.
But for me, the data on autism is extraordinary, because this is a disease that we know very, very little about. There is no way that we know how to treat this disease. It's a very complex disease. And there's been a small study, you know, but a very well designed study, showing definite differences. And a transferability of a phenotype. It's extraordinary.
Andrew: Yeah. And back, which is really important. So it's not just reversing it, but causing it. So you can show a sort of cause and effect relationship.
You'll be speaking about faecal transplants at the ATMS Functional GI Symposium in September 2019. What other things will you be covering there?
Johan: Well, I'm just going to really tell people how little we know, how fast this field is moving and by my sort of academic heroes, Professor Michael Kamm, who is... I've got two heroes Professor Kamm and also Tom Borody.
Johan: He's the most...he doesn't think out of the box, he thinks right out of the factory, that makes the box.
Andrew: That's right.
Johan: He's an amazing man. But Professor Kamm has said to me that he believes that the manipulation and understanding of the microbiome is going to offer the same breakthrough in medicine that we received from discovery of antibiotics. And he's not a man who is given to wild flights of fantasy. He's one of the best gastroenterological scientists the world has ever seen. And that's what he believes, and he's doing research which is mind-blowing.
I was fortunate enough to be part of one of these research projects. Where we looked at, ulcerative colitis and injecting stool into patients. Donor stool into patients with ulcerative colitis. And the extraordinary data which was published in 2017, in "Lancet’s Journal," showed that injecting stool into patients has the same sort of effect in stopping ulcerative colitis and controlling it, as things like steroids and anti-TNF antibodies. The best drugs, we can give the stool has the same sort of effects. So it's a genuine effect.
Andrew: And obviously, you know, it seems to be well accepted now about C. diff, associated diarrhoea, and related illness. But there was even a fight with that, you know, the orthodoxy pushed back. I remember now, it seems like oh, no, it's okay. But how hard is it to get the acceptance to move forward with the use of FMT, faecal microbiota transplant for other conditions? Like, obviously, you've got to be cautious because, you know, are you infecting them with something? So how do you know who to choose and what...
Andrew: ...you know, how fast do you push ahead or how cautiously do you push ahead?
Johan: That is exceedingly difficult because of particularly the neurological type diseases, the Parkinson's, there's some evidence, that it's important in Parkinson's, is schizophrenia, in MS. There's lots of diseases where this could be very, very important.
Johan: And patients have formed advocacy groups, and I get confronted and have been confronted by patients saying, "I've got difficult-to-treat MS I want you to do a faecal transplant." The data just isn't there.
We know there's two diseases where the data is good, clostridium difficile. And Professor Tom Borody, three or four years ago said to me that if you don't give patients faecal transplants for resistant clostridium difficile you will be medico-legally responsible. It is the standard of care and there is no doubt about it. So faecal transplant for C. diff, yes that is the best for recurrency but not for first time C. diff patients. But recurrent C. diff 91% of these patients do very well and get cured.
For ulcerative colitis, it certainly has a role. Do we give it first up? Definitely not, we try other things the conventional stuff. That definitely, Professor Kamm uses in his clinic and the data is excellent, it works very well. And it certainly doesn't seem to be dangerous in that setting.
To use it in other diseases, irritable bowel disease, there was a meta-analysis recently, which showed that it could have some effect. I think it's too early. Crohn's disease, even I'm not totally sure that there's really strong data for Crohn's disease. And then for all these other neurological-type diseases, there does seem to be something happening there.
The autism spectrum debate is extraordinary, and the data there is very good. But things like Parkinson's and multiple sclerosis and various other immune-mediated diseases, you know, hepatitis, for instance, alcoholic hepatitis, fatty liver disease, we know that fatty liver disease or non-alcoholic fatty liver disease is becoming the main reason for liver failure and cirrhosis. We've sorted hepatitis C out. Alcohol is still a big deal. But fatty liver in the U.S. and in this country, 30% of patients in Queensland have fatty liver disease. That's going to be the huge explosion of liver failure is going to be driven by fatty liver disease.
And these organisms are certainly important, the microbiome seems to be crucial in the development of fatty liver disease, type two diabetes. All these types of metabolic diseases, obesity, the microbiome plays a very important role there. How can we change the microbiome? We're not sure. We know how to do it, but is it justified? By doing a faecal transplant do we get long term changes in the microbiome? Probably not. Do we use the faecal transplant routes, the sort of yucky injecting it into the colon which I do? That's a very powerful way. It's a genuine, transplant. It's almost like a blood transplant. You transplant faeces into the colon of a patient.
The newer way of doing it is to give tablets, but you know, do you get the same dosage, do you get the same effect?
Andrew: Yeah, that's right.
Johan: We're not sure. It seems to work. What does the future hold for us? Probably sophisticated culturing techniques, probably, you know, bespoke-type capsules that you can get... they call them “crapsules”.
Johan: But capsules with specially designed organisms in them to address certain things. But it's absolutely fascinating.
Andrew: Oh, absolutely.
Johan: As an aside, we know we treat people with encephalopathy. Let's say you've got cirrhosis, you're an alcoholic, you've got encephalopathy so your brain is affected by your alcoholism. We've treated these patients for decades using something called lactulose.
Johan: Which is a sugar that gets into the gut.
Johan: And it ferments in the gut. We've always thought that lactulose works by making you know, people go to the toilet and emptying out the toxins. Probably not. It changes the microbiome. And one way of changing the microbiome in a positive way is to take a bit of lactulose. That's, extraordinary. I learned that the other day in the lecture given by a fantastic microbiologist called Georgina Hale and she just taught me so much. They say we're learning all the time, it's surprising you know. It's actually really exciting.
Johan: But you've always got to be a little bit frightened of hype. There's a lot of hype and a lot of overselling, and we've got to recognise that this is an important and a big field. We've got to recognise that we know very, very little. We're not even scratching the surface of the surface. We've got to recognise that we know virtually nothing about this atypical or extraordinary different sort of tiny organisms like the archaea and the CPR group of organisms. We know very little about them and how they interact with other bacteria.
And you know the future is out there. And we know that we can change the microbiome, we can change it by changing our diet, by changing our lifestyle. We can use certain probiotics, but the data there is a little bit limited.
Andrew: Yeah. Well, that's one thing that I'd love to scratch the surface with if we can get you back on to FX Medicine at a later stage Johan. I'd love to...
Andrew: Thank you so much, though, for joining us today. I must admit, like I listened to a podcast with you and Dr. Sam Manger on The GP Show, and I was absolutely riveted by what you were saying. I'd also urge our listeners to listen to that link and we'll put that link up on the FX Medicine website for everybody to access.
Because, you know, you covered so much there and I would love to cover a lot more with you in including where probiotics are indicated and where the evidence is lacking. And just how cautiously we need to tread. But also, other things that we can treat with faecal microbiota transplant where the sort of evidence is leading us. I'd love to explore that on another episode, if that's okay with you?
Johan: Well, thank you. I just need to say as a final sort of sentence that it's genuinely exciting. And I think this is a genuine breakthrough. And it's humbling as someone who's been in gastroenterology for a long time, that we sort of missed everything. It's only now that we've come across it... The first time I came across faecal micro... FMT was when I was giving a lecture about 15 years ago, and I came across that article by Tom Borody where he was treating ulcerative colitis by putting stool samples into patients. And I presented it to my audience and everyone burst out laughing. And I sort of said there's this guy Tom Borody, he's doing this and it's crazy, but the data are fantastic.
Johan: And that reminds me of a quote by Niels Bohr, the famous, you know, quantum scientist who said, "This idea is so crazy, it might actually be true." And that's what we're looking at. We're looking at this crazy idea that things growing in your gut, change your brain and change your liver, and change your everything. It's extraordinary. It's very exciting.
Andrew: Very exciting to have you on the show. Dr. Johan Van Den Bogaerde. Thank you very much for joining us on FX Medicine today.
Johan: Thanks for that, bye.
Andrew: This is FX Medicine, I'm Andrew Whitfield-Cook.