Symbionts and Pathobionts with Dr Mark Donohoe

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Symbionts and Pathobionts with Dr Mark Donohoe

The microcosm of  fungal and bacterial organisms living within and upon us is far more complex than was previously thought.

What's more confusing is that there seems to be no absolutes, no one bacteria or fungi is universally good, or universally bad. Some of the alleged "good guys" can do us harm, whilst conversely, some pathogens are now being investigated as forces capable of good rather than evil!

Today, Dr Mark Donohoe joins us to share why he feels the clinicians of the future will aim to restore gut biodiversity and immune tolerance in the fight against chronic disease and ill-health. 

Covered in this episode:

[00:56] Welcoming back Dr Mark Donohoe
[01:32] Introducing today's topic
[02:11] Defining symbionts vs pathobionts
[04:43] Segmented filamentous bacteria
[09:24] A lesson in tolerance and diversity
[16:25] Conundrums of testing
[17:20] The Gut: A critical immune modulator
[21:59] Disturbing host resilience
[25:29] Re-regulation and restoring biodiversity
[30:17] Convincing the medical community to focus on the gut
[33:03] The future potential for helminth therapies
[40:43] Not all candida is created equal
[44:08] Final thanks and summary

Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook. Joining me in the studio today again is Dr Mark Donohoe, an integrated physician of great renown who graduated in 1980 from Sydney Uni, worked around the Central Coast and this is where his interest sparked for integrated medicine because patients just weren't fitting into the boxes of diagnoses and treatment. And I always love talking to you on FX Medicine, Mark, because you bring technical subjects but you bring them back to what it means for the patients and indeed, for look at the function of dysfunction. So I warmly welcome you back to FX Medicine once again.

Mark: It's a pleasure. I have to do it that way because I'm a clinician and a proud clinician. So clinicians see the world differently from researchers, from other people. We touch occasionally and then that transfer of information from research to clinicians mainly, you know, doesn't work but sometimes you get really neat stuff and this, what we're talking about today with symbionts and pathobionts, this is fantastic. This is where the researchers in the micro biome and the clinicians really come together for a very, very powerful way. What we see in practice is going on in the gut and the gut is programming immunity, and it's just a brilliant story.

Andrew: So this...again, like symbionts and pathobionts. So let's first go into a brief definition of what these are.

Mark: Well, symbionts are probably easier to understand. Symbionts are organisms that exist in the gut, like we're...just keep it to the gut at the moment. These exist in all cavities and on the skin all around the body, but a symbiont is an organism that we regard as generally friendly to us where we gain from their presence, they gain from our presence, and we leave each other alone and there's no dramas about it. And so we see symbionts a little bit like allies in a war on other organisms. They and we work together to maintain gut immunology, gut integrity, absorption of nutrition, and everybody wins.

Pathobionts are a different group. We've been kind of putting them in the category of...these are not like we think of infection and invasion with the systemic immune system. Pathobionts are bugs that exist in a more tenuous relationship with us that, if all is going well, they have an important part to play in the ecology of the gut but if things go bad, they turn against us. And pathobionts are therefore not invading organisms because they're there all the time, but when things go wrong, these are the that turn on more aggressive immune responses. So the pathobionts are not invaders. They're there all the time. They're almost like, you know, terrorist cells. They are ready to go off at some time if we disregard and disrespect the ecology of the gut. And that's why the story is so fascinating. All the bugs inside us at various times are symbionts. Some of them have the capacity when we misbehave, when we torture them with antibiotics, when we change our diet...

Andrew: Torture them?

Mark: When we give tons of sugar, they have the capacity to go off in a way that teaches us a lesson. And you can even make the case, and I do occasionally, that humans are nothing more than a block of floats constructed for the benefit of the bacteria in the gut. They outnumber us, the genetic diversity is greater, and they play such an important role in things like our cravings, what we eat in our diets, our behaviour that you can make the strong microbe case that we were constructed by microbes. Mitochondria put in the cells, eukaryotic cells really functioning as a result of bacterial interactions. They constructed us to feed them and to both benefit and live a long life to construct an environment for microbes.

Andrew: Let's go back to birth or near birth. An organism that greatly interests me, segmented filamentous bacteria. 

Mark: Yeah.

Andrew: I mention these like you mention stewed apple. 

Mark: I know. I know. The SFBs. I think these have your signature, and I think that there was something in your childhood that has happened and we're not gonna go into that today.

Andrew: But there's something like...I remember when I first saw this work by Dan Littman and Ivalia Ivanof. Dan Littman, I think, is at New York State Uni. Ivalia Ivanof is now at Columbus State Uni. But what greatly interested me is the priming of the human gut, how a good guy could become a bad guy if you didn't look after it or if something else happened to rob it of a break. 

Mark: Yeah.

Andrew: Take us through just the shortened version of this. I mean, this is really interesting research and for an...we're going to be putting papers and papers and papers up on the FX Medicine website for people about this whole subject because there's so much to do with it.

Mark: And as I said, this is where research really touches clinical practice, knowing about this stuff gives a clinician the power to be able to knowingly, not thoughtlessly, disrupt change and maybe change the trajectory of inflammation in another human being's life. Not by treating the person, but by treating or managing the ecology of the gut. So, the SFBs are fascinating because they are both symbionts and pathobionts at the same time. The gut ecology is way more complicated than we had ever made out. 

Andrew: Oh, yeah.

Mark: We’ve said before in these, "Why is human breast milk so incredibly complex in its glycans?" You know, there is this thing about birth through a vagina and human breast milk and the breast milk seems ridiculously overcomplicated compared to most other mammals. We are way more kind of diverse in the glycans in the milk. When the mucan layer forms over the gut wall, it's not a simple bit of, you know, muck on the top. It's a bi-layer, there’s two different layers. The deeper layer is filled with the glycans, but they vary in different spots all the way along the gut. What it's like is a garden where you are planting different things in different areas and you are harvesting the benefits. So there is a temporal sequence of coming in the top end, low numbers of bacteria in the stomach and then you go down, getting more and more and more diverse and more numerous. And that is a consequence of a very sophisticated layering of the mucan layer of the bacteria that thrive in those particular circumstances with those particular glycans. And then an immune response which is so superbly developed. We call it innate and acquired, but in fact, innate immunity's not innate. If you have a sterile gut, you do not develop innate immunity.

Andrew: That's right, yeah.

Mark: You need these things which we think of almost on the edge of pathogens, these are clostridium organisms. These are difficult to grow, almost impossible to grow out of the gut. But they are numerous, they're filamented, and what they seem to do is induce an immune response which can pick's almost like an exercise program for the immune system. Pay attention to these, learn how to defend, get your Th17 cells in place, get the regular (Th)3 cells in place. If you are too nice as the bacteria in the gut, the immune response of the host is malfunctional. It is poor. It doesn't develop properly. So there has to be this kind of slightly torturing. We will cross...

Andrew: It's like a slap to wake up, isn't it?

Mark: Yeah, it is.

Andrew: It's like slapping the baby when it's born.

Mark: Well, I don't support that either, but it is an intentional stimulus. And reminds me of "Star Trek, Into Darkness" where Scotty says...he's talking about the machinery that drives it. It's like a bomb...

Andrew: Can't do it any faster.

Mark: It's like a bomb ready to go off at any given moment. And when you look at the microbial environment in the gut, what is amazing is that we can survive it. This is a bomb ready to go off. Why and how we do it has been the mystery and the solving of that mystery, the segmental filamentous bacteria, have an enormous part to play in that. They test the edges of the immune response, they help develop innate immunity in the gut, the Peyer's patches and the general submucosal immunity are both stimulated by that and they're stimulated to the point that they do not go over aggressive and they stay within boundaries and almost like a school, to learn what's normal on the other side of the gut.

Now, I wanna give a very brief story because many years ago I saw children adopted from Africa by parents who brought them along, good, integrated practitioner, we wanna do stool testing, we wanna find out what know, how these kids have managed, they’ve come from Africa, terrible environment. And what we saw in the stool test was pathogen after pathogen. It was...we looked at it and we thought, "How did these kids even survive?" Their gut flora is so distorted, so terrible, that we're amazed that they could even maintain weight. So we put them on probiotics, but what we put them on was probiotics for normal, western children.

Andrew: And milk-based probiotics.

Mark: Milk-based probiotics. You're quite right.

Andrew: Mostly milk-based probiotics.

Mark: Yeah. But what we did is we made a mess.

Andrew: I need to qualify that anyway.

Mark: We made a mess of these children. 

Andrew: Yeah.

Mark: We achieved a gut result that looked more normal. The children got so sick with it that they were really at risk of dying. And we had to back off and just allow for the fact that in their development, through their early year of life, the early years of life, their schooling had been in how to tolerate things that any Australian child would not ever have tolerated. 

Andrew: Yeah. Yeah.

Mark: And so tolerance was built. The SFBs are down there doing their job to say, "Yep. Here's what's normal. Leave these things alone. Do not go to battle with these or you will not survive." And so there is region to region variation which is going to be just magnificent research to be done across the world. How do we solve malnutrition? We get to understand the gut of the children who live in different societies with different foods, with different probiotic origins and we learn how that tolerance occurs to the things that we would be possible even fatal to Australian kids. 

So having said that, I'm just really making the point that depending on what your environment is around birth and in those early years of life, the segmented filamentous bacteria are critical to use sampling the world of the gut, developing tolerance to it, having the immune system ready to pick up on invaders that may disturb that tolerance, and it's not just SFBs. They're the most important one that we know of right at the moment, but there's also the two helicobacters, the hepaticus and the pylori. These are again ones that...organisms that will test the immune system and when the host is healthy, will stay in abeyance, they won't cause disease. When the host is out of balance, when the immune system is overaggressive, when, say, gluten for gluten reactive people comes into the picture, these are organisms that can become pathological and can cause, say, helicobacter we know, ulceration and maybe even cancer in the stomach.

Andrew: And that may be strain dependent as well.

Mark: It is very strain dependant.

Andrew: Really, really interesting work by Martin Blazer, one of my favorite microbiota authors. 

Mark: Right.

Andrew: Martin Blaser, looks at helicobacter pylora in another light.

Mark: Right. As what? How does he...

Andrew: As a commensal.

Mark: Yeah.

Andrew: You know, but, there may be strain issues, there may be terrain issues as you say.

Mark: Yeah. And there's certainly host issues. 

Andrew: Yeah.

Mark: And so that's the other thing that we do know about pathobionts is that they're not pathological in a healthy host where the strains self organise, where the immunology, the innate immunity and the acquired immunity learn the boundaries. And those boundary conditions around the gut are so, so critical. So if you think of the pathobionts more as testers and organisers and exercisers of an immune response that keeps the immune regulation up, that makes the immune response very definitely respond when a new pathogen crosses and it's ready to go. If you think of them that way, they're not really pathobionts. They are opportunists. They will take advantage of a host where the regulation of immunity has gone down. And where do we see that problem most commonly these days? We see it post antibiotics or with immune suppression when we give immunosuppressive drugs for, say, cancer or for autoimmune disease. Those are areas where we disturb that gut balance, and these are bugs which we have to pay much more attention to. In arthritis, with rheumatoid disease, with thyroiditis. The things that we are now being...becoming aware of is that gut and autoimmunity are so closely linked…

Andrew: Oh, yeah.

Mark: …that they may be the same thing, there may be no difference between gut and autoimmunity. And in clinical practice, truly, management of the gut has by far the most profound effect I have seen on diminishing inflammatory responses in autoimmune disorders like lupus and thyroid disease.

Andrew: You know, I've learned so much from Mike Ash on this...about the tipping point with regards to inflammatory based or autoimmune diseases whereby if you can get them just under this tipping point line, you don't have to get them way under. You can get them just under and sometimes their symptoms disappear. So that really discuses the terrain of the host and if you just get it healthy enough, that sometimes you can get...make a magical difference.

Mark: Well, that's what you would expect if there's a regulation process that goes there. It's when it gets disregulated beyond the point that we get symptomatic outcomes. 

Andrew: Yeah. Yeah.

Mark: And I wouldn't just say lupus patients, arthritis patients, they'll get better over night. They tell you, "My trajectory turned when my gut was under control." So it's not that the inflammation's gone 24 hours later. This is not like a drug. It's profound in the sense that once tolerance is reestablished, once balance is reestablished, they pick the time that when their gut was right, the arthritis, the thyroiditis, the energy availability, those things became normal or started to become normal again, it can take two years for that to work out. But it's...the trajectory has changed. They're not getting worse. They're getting better when the gut gets right.

Andrew: You know, this...I mean, it falls into the podcast that I spoke to with Clint Paddison and his recovery from rheumatoid arthritis. Basically, one of the key things that I took away from there was fresh foods. So it was...we're talking about what foods do to microbiota. But the other thing was getting rid of all, all oils. And I went, "What?" Because fish oil for me is a natural, as a health practitioner is something that you would automatically include. And he said, "No." Even avocados. Anything with a high amount of oil in it he got rid of. Really interesting stuff talking about which microbiota you are feeding.

Mark: Right.

Andrew: It would be so interesting to assay that sort of...what sort of changes he would be making to the microbiota...microbiome so that genetics signatures as well as the species...

Mark: Yeah.

Andrew: ...that are populating the gut. One point I would like to make that we spoke about SFBs...we're moving on from there, but about SFBs. And it's a point about we can't measure it, therefore it doesn't exist. You know, like this stuff was only just discovered because you couldn't culture it. So just because you can't culture it doesn't mean it's not there. Just because you can't see it on a poo test doesn't mean it's not on the wall.

Mark: Yeah.

Andrew: It just means it's not in the poo. So we've gotta think about relevant testing. That's another podcast you and I are gonna do.

Mark: It is.

Andrew: So, it's one of these conundrums about testing, particularly with regards to the gut. Do you favour...

Mark: Well, you do overrate testing, though. I mean, believe me...

Andrew: Yes, so do you...

Mark: You know, the medical model is we overrate testing and underrate the things that we don't know. What we don't know that we don't know has been a problem with the gut for maybe 100 years.

Andrew: Oh, yeah.

Mark: And so we discount it only to turn around in the early 21st century and say it's probably the most important modulator of immunology in the whole body. And what's inside the gut is more important than all the stuff that we've done on acquired and innate immunity, thinking of it as human immunity, whereas innate and acquired immunity are a negotiated response…

Andrew: Yes.

Mark: …between microbes in the gut and our immune cells. It is a balance between them and it's a gardener's balance. It is the same as our balance with soil and plants and foods. And I still come back to, “you know, eat foods, not too much, mainly plants.” That balance...I can understand where his problems with the oils may arise, but I still would say we know the short chain fatty acids are incredibly essential. Now, that is soluble fibre, and it may also be some of the oils that are in the diet. 

Andrew:  Which is interesting to me.

Mark: We can't get rid of them completely. What's that?

Andrew: Yeah. Well, it was interesting to me trying to ratify that.

Mark: Yeah.

Andrew: You know, the butrate equals butter or butter equals butrate. Take it out in rheumatoid arthritis.

Mark: Yeah.

Andrew: So but that may fall into this when there's a symbiont, a pathobiont. You know, I've been speaking recently with professor Steven Sandberg-Louis on the subject of SIBO. I've spoken previously before that with Nirala Jacobi, an expert in SIBO in Australia. And this is very often the good guys overgrowing, but it's because you've made it so. You know? That so it's kinda like how much does a host take?

Mark: Yes.

Andrew: How many hits does a host take? I'm reminded's touted that Lois Pasteur on his deathbed, you know, sort of whispered, groaned, "You know, it's not the germ, it's the host." Now, apparently...I've read up about this, and apparently he never said that.

Mark: No. It's unlikely he'd deny his whole life's work.

Andrew: Unlikely, yeah.

Mark: He's one of the most famous people. Yeah, so you don't do that.

Andrew: However, I think as you say, one of the greatest discoveries or acceptances in the early 21st century was that the gut is the seat of the major part of the body's immune system. Up to 80%, I was reading, including secretory IgA, and more important or more proliferative, is the IgG. But the IgA is non-inflammatory, whereas the IgG is an attack system…

Mark: Yeah.

Andrew: …if you like, a response.

Mark: And IgA's a protector front. A thing that just occurred to me then, what we are learning is it's not single cause, single effect. We're out of the time of the single cause for every disease. What's appearing whether you deal with planetary ecology or human ecology, gynaecology, is that diversity and ability to change over time... and diversity and adaptability are the hallmarks of a healthy person. 

Andrew: Yeah.

Mark: It’s not that there's a right microbiome. 

Andrew: We tried.

Mark: There’s a right microbiome for a season. There's not a strain that wins the battle. 

Andrew: Yeah.

Mark: There’s a disturbance and inability to adapt to that disturbance. And I think in many ways what we do as clinicians is we have...I don't know if you remember the old televisions, the cathode ray tubes.

Andrew: I remember.

Mark: When things went wrong, what you did is you belted it on the right and if that didn't work you...

Andrew: Hit it on the left.

Mark: Gave it a slam on the top and it worked and it got the picture back. So what we learned was, "Oh, you slam this TV on the top and that's what makes it work properly." We're at that stage still in clinical work of saying, "Wow, you've got distorted gut. What do we think that means?" Well, our tradition in medicine is to think, "Oh, that must be a pathogen down there. That must be a streptococcus, that must be an invader." And it seems like we were wrong, that mindset is a Pasteurian mindset that is now probably past when it comes to the gastrointestinal tract. Shigella, salmonella, there are bugs there which are pure invaders and what's our primary defence? The normal microbes of the gut. It's not...we are not defending ourselves with an aggressive immune attack.

Andrew: And our immunomodulators.

Mark: Most microbes do the job of pissing off the people...all the bugs that come along that are not welcome there that disturb that balance. So we rely on building a defence system where inflammation is not even part of what happens, where the normal microbes create the netting, the bio-films create the environment, which is not invitational to any pathogenic organism and in fact, they take them on. 

Occasionally, that gets disrupted and we get the diarrhoea, the shigella, salmonella. All hell breaks out. Immunology goes to work. The pathogens either win or they don't win, and then we restore normal balance. But those hits are not terrible for us. Our ability to take hits and resiliently come back seems to be the hallmark of good, healthy people.

Andrew: And that to me is the difference. You know, this is what Steven Sandberg-Louis taught me about of the aetiologies of SIBO was that, you know, a campylobacter infection, campylobacter jejuni. They recover from that. But because the toxins might be knocking out one of the motility stimuli, you've now got a motility issue in the small intestine where it slows down motility up here therefore allowing more fermentation. 

Mark: Yeah.

Andrew: You may get diarrhoea in the colon, but in the upper intestines you've got a lowered motility…

Mark: Yeah.

Andrew: …and this fermentation process going on. So it's just really interesting how you might "recover from it," but the long term effects are that you've now got a disrupted landscape.

Mark: Yeah.

Andrew: And it smacks to me of this, you know, the same sort of thing going on with complex regional pain syndrome. The wound's healed but the pain remains.

Mark: Yeah.

Andrew: You know? How do we get people back to a normal functioning from this? Really interesting treatment options.

Mark: It is not only interesting. I mean, when you raised IgA, immunoglobulin A is in fact one of the things that the segmented filamentous bacteria are part of the process of creating.

Andrew: That's right.

Mark: They make us make IgA appropriate...

Andrew: In response to it...yeah.

Mark: Yeah. Now it's appropriate to the regulation of themselves. So the extraordinary story seems to be some of the bacteria in the gut stimulate the response to pick a fight with them to keep them at bay. It's almost like, "We like being jailed here, we’ve got a happy gut. Keep us here, master." Unless you think of it the other way which is, "Master, what should we do to keep you here?" You can have it either one being the boss there.

Andrew: Yeah.

Mark: The helper cells, the Th17...we used to say that the CD8, the immunosuppressant...what we've regarded as the suppressive T lymphocytes. One out of every 10 cells in the gut was said to be CD8. So 10% of the enterocytes were in fact an immune cell that was not really the pure CD8. It was a regular three cell. We didn't have the sophistication early to understand that these are what we now call Th17s, the regulatory T cells. Those Th17s are not a pure line of cells, they swap roles. The Th17 can become a different expresser. And the regulatory lymphocytes are continually being taught by the pathobionts and the symbionts about what's normal and what's not. They rise and fall according to need, not according to absolute numbers. And healthy people keep on having rises and falls within a reasonable range.

Andrew: Homeostasis.

Mark: That's right. That helps us understand that the microbes regulate our immunology and our immunology sets the boundaries for those microbes. And I think the future of this...if you had the ideal thing...I'm not sure that this'll ever work out. Breast milk for adults, the glycans in there may reestablish it. We don't know for sure that that's the case, but it's not gonna pass TGA regulations. 

Andrew: No.

Mark: I’m just pretty convinced that you're not going down that path. What I could say though is beyond breast milk, we still have things like colostrums. You know, colostrums products and regulatory proteins that come in via the diet and it is remarkable how many people respond to good colostrum products. When you think of it, why would that be the case? These are cows producing immunologically modulating molecules for calves. But it just shows you that getting into the rough area of re-regulation and the gut given a belt on the side, a hit on the top or whatever it is we're doing, is capable of re-regulating itself. We don't have to nanny it back to perfect health.

Andrew: Yeah.

Mark: We have to get back a rough balance so that the IgA, the Th17 cells, the bacteria are all saying, "Okay. Balance is resettled. Let's go back to our cycles again." And they will rise and fall and we will rise and fall and that's not pathological. When it gets pathological, it's biodiversity is lost. We know that through some of the studies now that as genetic biodiversity of our microbiome drops...and I'm really hanging out for the tests that we can do with that. Not what's the specific strain, I know Bio Screen in Melbourne and others do this where there’s look, here's the strain, here's the bug. Why don't we attack that or why don't we do something about that? But I think the much more important number for a general practitioner or a naturopath is what's the biodiversity like? Is biodiversity in the gut good? And if it isn't, what can we do to stimulate biodiversity, get those segmented filamentous bacteria and the helicobacters back into their role of re-regulating immunity without doing any damage?

Andrew: So…

Mark: We get biodiversity in the gut. We get health. That's some of the studies done a few years ago in nature show that when you establish biodiversity, when you increase genetic diversity of the gut bacteria, c-reactive protein inflammation markers drop away, and that's associated with better perceived health by the hosts.

Andrew: Yeah, I think it's really interesting that notwithstanding that humans are one of the only animals on earth that doesn't wean and know, there may be certain choices that people have to make with regards to milk consumption. But I think there's a real and under-utilised place for the use of colostrum to help give a bolus dose of secretory IgA, IgG, lactoferrin, lactoperoxidase, those sort of anti-infective type whacks, you know, a smack on the bum sort of thing. When you have a clinical need to do so as a reset. 

Mark: Yeah.

Andrew: Not for, you know, forever and a day, but as a short-term sort of usage. And I I have gotten such brilliant results particularly in short term infections, but I do wonder about the use of things like saccharomyces boulardii, LGG. They're known probiotics. They can stimulate secretory IgA. Glutamine can stimulate secretory IgA and the healing of the gut.

Mark: And interleukin 10. I mean, the IL10 is an important component of immune modulation on the gut as well so...

Andrew: So what would you give to induce IL10?

Mark: The saccharomyces is a good example. I mean, one of the values of the saccharomyces. But there are a bunch of different bacteria. It's not one. It's that we're trying to change the game down there from a pro-inflammatory tendency where the low grade stimulation of the pathobionts is enough to keep turning things over in a negative way for the host. How do you change it? We're still in a crude area of research which says, "Well, this looks like biodiversity improves things." What does that mean? The only paper that we really have, still, is cut all the sugars out, go to a high fat, high protein diet temporarily. It reduces bacterial numbers, but it increases bacterial diversity in the gut. And remember, through all of this we haven't even touched on the other microbes in the gut. 

Andrew: No.

Mark: We’re still talking about the microbiome as though it's only bacteria. There's a 100 viruses…

Andrew: Fungus. Viruses.

Mark: …for every single one, for every single bug. We are grossly outnumbered.

Andrew: Archaea.

Mark: We have the archaea. The methane producing archaea which is again a fascinating group. You know, the bacteroides firmicutes...I call them firmicutes.

Andrew: Firmicutes.

Mark: You say firmicutes, I say firmicutes. I think firmicutes is a great name. But the bacteroides firmicutes and the methanogens. And so we've got three big classes that have tended to dominate the human gastrointestinal tract. Everyone knows what methane's like, plenty of people have lit it at parties at various times in their past, so the archaea are critical to a part of the function there as well. So we have two different kingdoms or domains of life within us. 

And we've acted for all of our scientific careers until the last decade as though they are irrelevant to life, whereas now I think we're finding they are critical to what we regard as health. What we perceive as health is largely to a great part determined by what goes on in the gastrointestinal tract and getting that right is now the job of every good clinician. I think you won't get much argument from natural healthcare practitioners or integrative doctors. 

Andrew: Yeah.

Mark: But it has been so hard to convince the medical community that it is not a methotrexate deficiency or a prednisone deficiency. We used to call prednisone in the 1980's "vitamin P" in hospitals… 

Andrew: Yeah. Yeah.

Mark: …because we knew that you could suppress immunity for everybody. And what we did to the guts of people with that process over that decade where we thought, "Hey, we've got a magic answer to everything as we can turn off immune responses." The cost of it is just horrendous and we’ve seen…

Andrew: Look what we've done with antibiotics.

Mark: Yeah. I have a major concern about that. 

Andrew: And now…now…

Mark: What I will say, I was wrong. I don't...I've told this story before. Tom Morodi, Center for Digestive Diseases, back in the 1980's, I was seeing people going to him and getting these antibiotics and I was convinced, on principle, that this was a terrible and harmful thing. And we did work. And those 42 patients and the specifics of it were more than 6 months of continual antibiotics, sleep disorders, gastrointestinal problems, mainly irritable bowel syndrome, not ulcerative colitis.

Andrew: Yep.

Mark: Prior to the onset of this treatment and the faecal transplants with a single given host for those people was transformative. It changed my mind, and it's not easy to change my mind. You know, I sail in a direction and it goes that way until something's really powerful. But that transformed 38 of the 42 people's lives in terms of fatigue, sleep and gut. And I had to admit that I was wrong.

Andrew: But a very expensive option.

Mark: Well, not just very expensive. It didn't work on the redoing. So everybody that got well and said, "Gee, I'm glad I did that." And there were some downsides to it, but everyone that got well eventually came back at another time. Either they had antibiotics or under stress, something went wrong. And they and I both said, "Oh, let's get back and let's do it a second time." And the second time was nothing like the first time. It almost never worked. So for me the lesson was you can do a disruption, you can do the atom bomb once. You can't go back and do the atom bomb approach again and again. And we have to learn something that is different that reestablishes this balance of the pathobionts and the symbionts. And it's not as easy as just pressing the reset button and everybody returns to normal.

Andrew: Just quickly, there's two other areas I wanna cover. One of them we've done a separate podcast on, but I do wanna cover off a little bit on and that's Candida. 

Mark: Yeah.

Andrew: But the one first that I wanna talk about is helminths and the prospect of their use. Particularly in autoimmune conditions but in other conditions as well. I think one...

Mark: Coeliac disease.

Andrew: Coeliac, yeah. I was looking...celiac. So where are we at? You know, there's stuff...there's work done by Monash now at James Cook Uni.

Mark: And I have patients. I have patients on these. You can purchase these from centres overseas or particular helminths that have got particular specificity for particular diseases. It's at the beginning of this whole story I think. But that's what I said. The other bugs that are in the gut, we've had to focus on bacteria simply because that seemed doable. You can test the genes, we know bacterial genes, it's hard to pick viral genes, and it's really hard to pick what the impact of bigger organisms, the Candida and then the multi cellular organisms like helminths. 

But what I can say is that at the clinician's level, people with the helminth infections are protected against a lot of allergic disorders. I have people that have very high potential for allergy, and when you see the raised eosinophils and you see the raised IgA...I'm sorry, IgE, you think, "Hm, is this really allergy or not?" Their story was severe allergy. When they get the helminthic infections, they in fact put all of those resources towards looking after helminths and they leave the allergies alone. 

I think in autoimmunity it's gotta be a little more complex, but the initial studies...because these laboratories do give out the studies which show that there was alteration of that. For coeliac disease, it's pretty good evidence that you can do something which changes the regulation and inflammation in the upper part of the gut where you get the disruption of the villi. For thyroiditis, there's even some inflammation that says these may alter the trajectory of autoimmune type processes elsewhere in the body. Coeliac disease is an autoimmune process. So, you know, we thought of it as tropical sprue and there is something that takes it to the gut wall. But of all the people with Coeliac disease genes, the DQ2 and DQ8, only 10% ever get Coeliac disease, 90% don't. But they do get thyroiditis.

Andrew: Certainly it's a primer.

Mark: At a very, very high level. So one line of thinking is you have distorted gut immunity. You then get a bug that comes along, say a yersinea, and then yersinea is very specifically similar to the thyroid and so in susceptible people with these DQ2 and DQ8 genetics, yersinea in the gut triggers a thyroiditis. And we know that more than 50% of females with those genes end up with...if they're gluten eaters, end up with a thyroiditis. So there's a whole interplay. What's in the diet? What's your genetics? What are the microbes that you developed at birth and how do you culture those microbes? It plays out as a very complex time series and we as clinicians are left with a point in time where a person comes and complains to us. Why do I have three hour consultations? Partly because, at the beginning I need to know what was your early history of life? Were you breastfed, was it a vaginal birth, did you go to preschools, were you sick all the time? These are questions that when you have time to ask them, it entirely makes sense. 

So what happens as an adult? Even people in their 60s and 70s, we can trace it back to those kind of origins and where the illness originated. And I will put it as about 50% of the time that the gastrointestinal tract has taken the hit at inflammation, the origins of those inflammation are with the gut. Even people who've got used to it, you ask the specifics. “Do you get diarrhoea?” Oh, yeah. I get diarrhoea every couple of weeks.” “Why?” “No idea. I've had it all my life.” That's not normal. 

Andrew: Yeah.

Mark: You won't get diarrhoea all your life. You may get used to it, but that doesn't mean that it's normal. The more common presentation is people saying, "I get bloating, wind, and constipation." We used to say, "Oh, that's Candida. You know, if we give an antifungal, we're gonna get you better.” What it was is I think more like we're discovering now with SIBO, that there is peristalsis changes, there's gas production and there's fermentation, and that hurts. There's almost nothing in the gut that really hurts apart from that stretch receptor. So what we may be able to get and this, you know, relates to the Bioceuticals Symposium this year, if we get an understating of how that process of gas production and peristaltic loss happens, then doing something about that...and I would be hoping that the symposium is not gonna be, "Oh, just give antibiotics for it." Because refaximin is the kind of darling of our profession right at the moment. We give that to people and they get better.

Andrew: No, there was some very interesting study on SIBO looking at herbs, and basically herbs worked as well if not better than refaximin for SIBO. And there was a whole antibiotic regime know, I think Steve Sandberg-Louis said it was on 600 odd people.

Mark: Right.

Andrew: So a really interesting study. Again, we'll put that up on FX Medicine website for our listeners to access.

Mark: But it's a good reason to attend this year's symposium.

Andrew: Oh, absolutely.

Mark: You know, dealing with those areas of gut and the management of that, that is the job of sustaining normal immunity, normal nutrition and building health. And without those three...yes, there's genetics to it. People are predisposed to get autoimmune disorders and Coeliac type disorders. Get them off grains early in life, that seems to not progress at all. So I think there's gotta be value to us understanding the genetic predispositions of inflammation and getting advice to parents in the early years of life, "Don't put your kids on Wheatbix" It's the very first thing you do after three months of breastfeeding. Do have vaginal births, do breastfeed for as long as possible. Get them onto vegetables and things which are going to build normal immunological tolerance down in the gut and then later on, when they're teenagers let them go and try bread. It doesn't seem to then set the trajectory for the thyroiditis, and the autoimmune, and the Coeliac-type disorders later on in life.

So we have to learn new tricks as doctors. We're not just treating the person in front of us. We're treating the generation behind and the generation ahead, paying attention to what is inherited, paying attention to the process of birth, glycation, kind of giving the right glycans in breast milk, sustaining the health of mothers. What did we hear just this month is the new initiatives in diabetes focus on pregnancy and breastfeeding as the way of managing the diabetic crisis. That's a transformation. But it means we're paying attention to the right thing for a change. 

So that's the clinical work. What you do for the person...I am keen to find out the non-drug approaches to SIBO in the symposium. I'm very keen to find out what we can do for an individual. How do we separate one from another and why one gets sick and why one does not? And how do we get the symbionts up? The symbionts are those that in large numbers settle an immune response. They don't stimulate it. They allow you to get back and there's really good evidence that we can do stuff about the big ones like ulcerative colitis, and Crohn's disease, and Coeliac disease, that manipulation of the bugs whether they're helminths, whether they're other bacteria, whether they're the kind of segmented filimentis bacteria, that we can change the trajectory's of things that we regarded as the domain of specialist gastroenterologists in the past.

Andrew: We've and I have done a podcast on Candida previously, and I just wanna quick sort of wrap up if you like of Candida albicans, glabrata, or tropicalis. You practice in Sydney. Tropicalis is said to be not very common, but I wonder if there's gonna be a geographical difference in the more tropical areas. And that's not to think about living outside the body, but talking about how the body has to cope with a hotter environment…

Mark: Right.

Andrew: …wearing clothes. Does it favour that sort of the growth of the Tropicalis in a higher...sorry. A lower latitude nearer the equator?

Mark: Yeah, a lot's gonna happen as global warming occurs. 

Andrew: Tropicalis everywhere!

Mark: And, you know, the global warming of our internals is probably gonna be down the line. There are changes in the distribution of these.

Andrew: How does treatment differ as well?

Mark: That I don't know. So I can't honestly help you out there. I see mainly when it's pathogenic. The candida glabrata species are the ones that, shall we say, keep on popping up?

Andrew: Right. 

Mark: And the Candida albicans, these are on that borderline between commensal organisms and invasive organisms.

Andrew: Yeah, yeah.

Mark: I still to this day see Candida as...Candida and the variants of it as mainly a problem for Richie Shoemaker's group of the highly yeast mould reactive, the microtioxin reactive. Some of us go off like a firecracker when yeast and moulds are around in small numbers whether inhaled, ingested, or any other way. And that's a loss of immunological tolerance which is exactly what we've talked about all today.

Andrew: Yep. Yep.

Mark: How do we reestablish that tolerance for a person who's pushed beyond that edge? I see it also as iatrogenic disease. Our use of steroids, our use of antibiotics, our use of the oral contraceptive pill has primarily made the vagina the ideal breeding ground for a lot of women to develop these fungi. For many it's innocuous. For others, it is a lifelong battle, but the gastrointestinal tract and the vagina are never settled. They're always in a state of low grade inflammation. 

And for those people, Candida treatment is not killing all the bugs. It's giving its competitors a chance to flourish and bringing the numbers down to that tolerable level. And then what we do on the human side is how do we induce tolerance? Now, I think that's gonna be played out still on the gastrointestinal tract much more than it is with drug therapies and the things that we've done in the past. In the past, we crudely hit it all with drugs and with herbs and with diets. I am a big fan of low sugars in the diet. Low, free sugars. Especially things where there is a fructose and a glucose component together.

Andrew: Yeah.

Mark: Those are probably the primary ways that we are going to manipulate the gynaecology and inflammation control. And if we can get a good, stable answer about what we could do to provide energy for people, provide the foods that they need and get them to break that sugar addiction which is a whole generation in coming. If we can get that to be broken, we can establish normal inflammatory response control on the gut. We'll put the rheumatologists out of business. Truly. The gastroenterologists and the rheumatologists should be living in the same building. They should be mating and having children that cover those two specialties because the gut and autoimmunity and inflammation, that's where the future of this lies.

Andrew: Dr Mark Donohoe, thank you so much for taking our listeners through the quagmire of the symbionts and pathobionts or at least some of them that, you know, pop up from time to time and cause issues when the host just isn't at its wellest, if I could say that.

Mark: I have a simple mind of a clinician. I think that that's it. The focus on a patient, the person in front of us, really clarifies a lot of stuff. This is complicated, but in the end, people that you do something to who get better come back and tell you that they've done better. And a sense, we can kinda bleed research, as well as follow it. But when things work, lots of things that are in research don't, but these things of managing the gut, it's transformative to any doctor or any practitioner who ever get...starts to get it right. And it leads you to do things like, you know, be a proselyte for stewed apples, for example. Once you find tools to do this, it's addictive, and people's health recovery is just transformative.

Andrew: This is FX Medicine. I'm Andrew Whitfield-Cook.



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Dr Mark Donohoe

Dr Mark Donohoe is one of Australia’s most experienced and best known medical practitioners in the fields of Nutritional and Environmental Medicine. He has a long history working in the emerging field of “integrative medicine”, and continues to bring orthodox and complementary medicine together in his medical practice. He is a regular guest on the FX Medicine Podcast and in 2019 became the host of FX Medicine's newest podcast series; FX Omics - blending genetics into the modern practice of personalised medicine.