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Probiotics as Medicine

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Probiotics as Medicine

In this episode Mark Donohoe reviews key, evidence-based probiotic and nutritional therapies for the management of irritable bowel syndrome, Helicobacter pylori infection, ulcerative colitis and Crohn’s disease. He also explores the latest developments in faecal transplantation for the treatment of Clostridium difficile infection and inflammatory bowel disease.

Covered in this episode

[00:57] Welcoming back Dr Mark Donohoe
[01:44] Probiotics and inflammatory disorders
[04:15] FODMAPs and elimination diets
[09:55] Feeding the gut bacteria
[13:59] IBS and probiotics
[18:51] The art in building your own health
[24:46] Gluten and irritable bowel syndrome
[28:14] Gluten and thyroid dysfunction
[29:57] Helicobacter pylori, Triple Therapy and the war we can’t win
[37:28] Reimagining conventional gut treatments
[42:30] Faecal transplantation 
[44:10] The future of gut health lies with gastroenterologists
[50:40] Mark overviews the protocol of dietary changes and probiotics he uses for his patients
[58:20] Closing remarks

Andrew: This is FX Medicine and I'm Andrew Whitfield-Cook. And with me in the studio today is Dr Mark Donohoe, a GP of great renown who treats very complex conditions nowadays because his history was looking into patients, or the symptomatology and the presentation of patients that have things wrong with them that didn't fit into the medical paradigm. So welcome back, Mark.

Mark: It's good to be complex, isn't it?

Andrew: I don't know. Mark, today we're gonna be talking about the opportunities and the conundrae or the conundrums that we can come into when using probiotics, particularly for medically diagnosed conditions. And you've had a lot of expertise on this, particularly because you have very complex presentation of patients.

Mark: Yes.

Andrew: Take me through firstly what you use probiotics for and segment them out as to...like a stratification, if you like.

Mark: I can take you through the simplistic view which is complex patients typically have seen a lot of practitioners. Orthodox, medical and complementary, integrative and I'm at the end of a long line and typically, they've been through dozens of treatments. Nearly all have been on probiotics of some type or form along the way. They've heard of them and they know of the value. 

When I see people with chronic inflammatory disorders...and I think now it's getting clearer that things like chronic fatigue syndrome involves neuro-inflammation, it involves other inflammatory processes of the immune system as well. When I see those, I used to think of “how do we control the immune system” and think of it systemically. Now I think of it primarily as "how do we get the gut to be involved in the immune modulation?” 

And bluntly, when I am clear about what the cause of a person's illness is, I will often go for that specific treatment. But for 90% of the people who see me, the very first thing I do while awaiting the result of the testing that I do, is get them on really quite high dose, you know, up in the 400 or 500, even a trillion units, colony forming units per day and the Saccharomyces.  

And I even put them on Mike Ash's old apple, stewed apple which has proven a real boon. I mean, the number of people A, who say, "I didn't know I could eat apple and it tastes delicious and I'm feeling better." Balanced against a couple of people who really need the FODMAP type approach who felt terrible and got cramping pains and I regret. But for the vast, vast majority, that stewed apple has actually been a real boon in getting compliance and getting people interested in cooking and getting their gut back in order. 

So my typical thing is if we've got inflammation to control and there's evidence of standard things like C reactive protein, or the ESR has proven to be raised, or you've got this CD4:CD8 ratio which is high with low suppressor cell numbers. When you’ve those indications to me the gut and probiotics is the number one way of getting a quicker... come that first month while they're waiting for results, while they're trying to do something good for themselves. It's the quickest and best way to get people to say, "I never knew that I can feel that good in such a short period of time."

Andrew: Can I ask you a little bit about the FODMAP diet and that, you know, the stewed apple which really doesn't fit into that?

Mark: I know.

Andrew: And I, you know, I take my hat off to the work of Sue Shepherd and others who designed this diet looking at fermentable oligosaccharides, monosaccharides…

Mark: Yep.

Andrew: …and polyols. Forgive me.

Mark: But I still think it's a...FODMAP is a terrible name. Every time I...I feel like I'm talking about a Muppet or something like that. Yeah, yeah, this is a FODMAP. But you're right. We should be aware that many people have found that brilliantly good for managing their symptoms.

Andrew: And particularly for irritable bowel syndrome. That sort of seems to be where it's found its place. However, I have concerns about long term avoidance of healthy food groups.

Mark: Sure.

Andrew: And I think we should always be looking at why did this happen and what can we do to heal the issue so that I don't have to avoid those healthy foods.

Mark: A FODMAP diet in many ways is a medical model of there is a “right diet” and people should be on the right diet and there is no such thing as a right diet. If you are not able to manage fermentable oligosaccharide type of foods, the deeper question is “Why?” 

You can always put a person on a diet. In fact, you remember a well-known hospital around Sydney, the low salicylate diet. People went on basically no vegetables, no good foods for their health and felt great. But the fact is, if you stick anyone on no food who's got a gut problem, they feel great, temporarily and then they get malnourished. And then you are stuck with a problem of “how do we restore a healthy diet in this person?”

My concern about my medical colleagues is that they're very quick to criticise naturopaths for candida diets and, you know, paleo diets but they stick them on horrendous diets as far as long term health and maintenance of health goes, and act as though it's medical, therefore you should follow this as if it were a prescription for the rest of your life. And that of course is not true. 

The deeper question of why they need to be on that special diet can be answered and this is what, you know, next year with Dave Perlmutter and Alessio Fasano, this is exactly why we all need to be there. To hear the deeper reasons, what goes on with the genetics of the person who needs a wide variety of foods right through the early years of life. How to not end up as a FODMAP victim, in the sense, like where you are stuck on a diet which is not good for your health. How to consider grains, genetics, a variety of diets so that we're not talking about the diet right for everybody. We're talking about individual needs, how they get into a mess, and how you rescue them from that mess. And a FODMAP might be a good temporary diet but there is no way that that's your long-term diet for life.

Andrew: So it's a rescue effect.

Mark: Yeah.

Andrew: Or a rescue mechanism until you can figure out the cause.

Mark: Which is what medicine is largely about. What are we about? We're about diagnosing and relieving symptoms and getting a result early on. And my own profession's failure I think, is asking the second question, but why. Why in this person? And to me, the time that I get to spend with people, you can always see exactly where these problems arose. 

Sometimes it's in childhood with acne and antibiotics. And you could kind of understand then that a child with a six month course of antibiotics who didn't feel terribly bad at the time, but whose health problems and inflammatory problems and behavioural problems started appearing after that time. When they stopped their antibiotics, they missed something vital and that was the restoration of normal flora and normal gut biology.

And so I...to me, starting with what diet can make you feel better is one issue. I routinely take people off their gluten. I routinely take people off their milk. And when they say, "Oh, but I've been off it before." I have to ask, "Seriously? Have you?" And, "No. I was off it for a week but I had a bit of pizza during that time but I never noticed any difference."

And in practical terms, I have to say, "You need to be really serious as if I was giving you a pill that was gonna kill you. For the next month, you don't touch it." And we see what happens over that month. Now I would estimate that way more than half of my patients come back and say, "That is unbelievable. I could never have imagined that a diet plus a probiotic could allow me to feel good for the first time in my life." 

And so the practical issue is, if we can do something that starts to restore the ecology of the gut and restore digestive processes, and it could be done that easily, being strict about it for one month is an excellent idea so that they get the positive feedback. The other value is at the end of a month when a person is feeling good, you say, "Oh, try gluten again." And horrendous things happen which really reinforces for them that this was not just me limiting my diet. There are specific gut immunological reactions to gluten that they then are not all that keen to go and replicate over and over.

Andrew: I think one of the things that practitioners have gotta be mindful of when they're recommending any elimination diet is that the symptoms of having an offending food, particularly while you're on that elimination phase, it may not present immediately. It may present like two, three days afterwards. 

Mark: Yes.

Andrew: So if they say, "I had a little bit of pizza and it was okay. But then three days later when I had your diet I felt bad."

Mark: Right.

Andrew: And this is the problem. They say, "So the good diet made me feel bad."

Mark: Yeah.

Andrew: But it was from the three days earlier when they had that pizza.

Mark: Remember, there's something even deeper. There's the addiction/abdiction response, right? Why do we eat pizza? Well, there's a bunch of bugs down in the gut there that are really used to getting their hit of whatever it is you're about to give them, and you make them happy, little sausages for a while. They don't complain. 

When they lack their foods, they go a bit berserk. They're looking for something and we think we have cravings for pizza or sugar. I'm betting that the majority of the time, that's the bugs that are getting uncomfortable down in the gut. There is a gut feeling that you've got to eat a certain type of food to satisfy them. And this comes back to sugars, it comes back to grains, it comes back to all kinds of things that there is an addiction response which is very real. A person feels temporarily better on something and when that food is taken away, the gut bugs give their little messages, they signal the nervous system, cravings start to occur. And when you give into those cravings, it's really easy to think that the food is good for you and it's the not having the food that's bad for you. 

So in those first days I am used to a kind of process where I say to the person, "You're gonna come off this." About day five they say, "I've never felt worse in my whole life. How can you possibly say that this is..." Stick with it, stick with it, stick with it. And it is remarkable. Once the gut is clear, once the microbes start to redistribute themselves and the ecology returns to normal, that's when you start to get a chance for gut healing. And give them a month, give them the SB, the Saccharomyces boulardii, give them a decent dose of the normal acidophilus, Lactobacilli and the Bifidobacteria. Give them that and allow them just to reconstitute. They're not repaired in a month but what they do is feel better enough to say, "This is something really worthwhile."

And I do feel that that actually makes a difference to it. I'll also have to admit that at the end of that month when we see the pathology, you often see things like viral infections and altered function, kidney and liver function and it's not all to do with the gut. But the gut is such a quality good start, simple to do, takes the medicalisation out of it and gives them a story. If you have them stewing apples and looking for ancient grains or even grain free living, it actually gets people working. 

I saw a gentleman the other day I hadn't seen for two years. He came back and he said, "I just wanted to check up. Two years ago you told me to get on to fermented foods and to look after the gut." The guy had transformed his life and was back at the gym and putting on weight, doing everything. Still hadn't fully recovered but he got right into the whole process of making his own foods. And what was clear is, food had become a centre point for the family. They were making living foods, they were fermenting their own. He was experiencing the ups and downs of that. And over a two year period he needed no medical care. He never even came back for his results because he felt so good.

So I finally got a chance to re-medicalise him in the way doctors do and say, "Well, you know, we should just check that you fixed these." He's fixed them all.

Andrew: Wow.

Mark: And that is one person without training of any type, who just simply got interested and said, "I am going to pay attention to my gut, to food, to preparation of food." And that's the other remarkable thing. Families who pay attention to food, who do the cooking, who learn about living foods and learn about food cultures...there is a culture to every culture. And learning it and understanding how we manage our gut and re-inoculate it and how living foods play such a big part in our health, is I think the future of food in medicine.

Andrew: You mentioned the nervous system when we were speaking about the FODMAP diet and that perfectly leads into irritable bowel syndrome as a medical condition. And one of my issues has been that practitioners try and look for the magic probiotic, the magic organism, one organism for irritable bowel syndrome and yet when you look at the data, you've got positive studies on a number of organisms and even combinations of such when you give them like...for instance, I will mention a brand here, VSL3 because it's a product of medical level evidence for certain conditions but...

Mark: Sadly, lost from Australia to America and hard to get.

Andrew: Yeah, that’s right.

Mark: Very difficult to get.

Andrew: Well, you can't get it in Australia at the moment. They've come out with a weird sort of copy but it's not the same. But anyway, it, you know, may be down to dose so, you know, whatever. 

But there's VSL3 used in irritable bowel. There's, you know, Lactobacillus rhamnosus GG failed. Lactobacillus plantarum 299V had some positive effect but not with all parameters. Same with Lab4 combination of species and strains that had positive effect on some but not all parameters. And there was also Bifidobacterium infantis 35624.

Mark: Oh.

Andrew: Yeah, and this is...

Mark: The 35625 failed miserably but...

Andrew: But that was a good paper because it was Eamonn Quigley's group and he does really good writing. The lead author of that paper was Whorwell, PJ Whorwell and it was published in the American Journal of Gastroenterology in 2006. So just if anybody wants to look that one up.

But I fail to see why people want one organism to do all jobs.

Mark: Yeah. I mean, us doctors, we always like the purified version of something. Something with a long number and a patent behind it makes doctors feel comfortable. All the way from cannabis to, you know, probiotics. There's something about technical numbers that comes from our learning in medical school and reading papers and seeing very specific things done. 

And my reading of the literature now is that the foods play a...a prebiotic type of food environment plays an equally if not greater importance than the selection of the bugs. There's a degree of self-selection and mass action that's going on in the gut, of trillions of organisms changing around in periods as little as seven or eight days. You could get really massive changes of the microflora balances down there. And a lot of that seems to be driven by the glycans in the various foods that we have, and probably also the fatty acids. And even right down to the amino acids, you know, the conversion of leucine into factors that prevent sarcopenia. 

There's a lot going on down there of what we feed the bugs and I get the feeling that we are on the periphery. What we're doing with the microbiome project is we're looking for the magic, when the magic is actually on the dinner table. The magic is right before us with people relaxed, eating their food, salivating properly, chewing properly and they build their own flora based on that extraordinary combination of social, cooking and other skills. 

Still I say Digby goes out for a walk with me. My little dog knows what to eat. Possum poo is popular when things are going wrong for his gut and he normalises himself in a way that I would find disgusting but animals know how to do this. They get a direct gut brain reaction. They respond to it directly. We complicate it with a whole science which goes down to the sub, sub, sub, sub, subspecies of a species of a genera, and we think that that is going to be the magic. And I really strongly disagree. 

I think...I even strongly disagree sometimes there's the kind of prolactic acid versus no lactic acid production. And it may be in theory important but the bigger issue of getting the diet right and not focusing on the problem of the gut, but restoring normality of the socialising, the eating, the family gathering, the enjoyment of food. If I have one problem with FODMAP and salicylate and other diets is they can turn food into the enemy. That you actually then have people looking at labels fearing the very thing that's going into their mouth. 

And that fear inhibits salivation, it inhibits gastric acid production, it does a whole range of things to our digestive system which are not good for health. And we really have to get around that. Intervene with a diet, find out what your risk factors are, achieve certain goals and then broaden that diet out to the best that that individual, that family, or that social group can manage. I think that's gonna be the way of the future.

Andrew: Absolutely. I think if our listeners want to tune in to how fermented foods can become part of our active lifestyle, there's a great podcast by Dr Sarah Lantz on Buchi Kombucha and what she's done with fermented foods. There were some other great ones. I can't remember her name, she’s an American lady and she basically said that she's going in for a colonoscopy and there's certain things...five things that she's going to do afterwards to help promote her good bacteria. Avoidance of certain foods, inclusion of others like the fermented foods plus probiotics.

But I think you keyed into something that we really do miss out in our stressful 21st century living and that is preparing ourselves for the meal. Now I'm not a religious person but the act of saying grace...if we wanted to take the religious inferences out, the act of saying grace, just giving thanks for a meal, being in a present spot and relaxing into the moment. And if you wanted to take it out, just put a, you know, a white magic around you and just say, "The stress of the day will be there when I come back. Right now I'm gonna eat a meal."

Mark: It is difficult, right? And I say this from the perspective of a parent of teenagers, the last one of whom is just finishing her high school certificate, and in those circumstances stresses of my work, of my wife's yoga work, of the stresses of exams, of everything, mean that you've got to put the effort in. But integrative medicine is that one area that says that effort is worthwhile. Giving permission to patients to actually spend time on food, it seems almost like an evil luxury, you know. How can I spend the time making food? Well, if you want your health back, that's step one. The stewing of the apples. Michael Ash's idea, the stewing of the apples. The stewed apples gets people back into the kitchen making a recipe, having food that they love the taste of and feeling, "Hey, this is not only okay for my health. This may actually be supporting good health."

Andrew: Yeah.

Mark: It improves things like salivation. It improves anticipation of a food. It improves the way we sit down to eat a meal together. And it's a discussion point. How… whoever knew that something as simple as green apples stewed up with a bit of cinnamon and other herbs in there could possibly be so good for your health. People discuss it, tell their friends. Other friends take it up and it spreads metastatically through a community, through a suburb. Neighbours take it up. 

And building health is an art that we doctors I think have almost lost. I think naturopaths still hold it and I have concerns when naturopaths and complementary practitioners almost want to be disease treating just like doctors. They want to have hard, solid evidence whereas I would say 80% of health, maybe even higher, is built from the lifestyle that you live. Getting out, biophilia, getting into the outside air, walking, exercising, enjoying and making your own foods. I think the extra step of living foods and fermented foods will become something that's so common to health management and eventually is starting to be delivered by their gastroenterologists of all people. They are seeing the benefits in the literature and saying, "Well, how do I translate that?"

Now I'll tell you the problem. I as a doctor feel embarrassed when I say, "What you've got to do is sit down with your family, eat. You take your time, you prepare the meal." And they say, "But what's the treatment?" So the patient says, "Yeah, yeah, yeah. But that's all the soft stuff. That's all anyone can tell me." To be a doctor and to not run straight to a pill or potion or a strain of a probiotic is a really difficult thing, because people walk away thinking, "That's just low grade information." 

Until they experience it where they realise that the rebuilding of the health...you're handing the ability to look after their health back to them and that's a really valuable long-term thing because it cuts their medical and integrative costs. It costs nothing to prepare food well except the time and the effort that you put into it and that's paid back by good health.

Andrew: And I've gotta say in my experience I've been so impressed when a GP takes the time to go through the basic, even evidence based parameters which they should be covering first before going for pill. I'm so impressed when they actually take the time to talk about the importance of diet in health related conditions.

Mark: Yeah, it is...the doctors that I talk to say, "Oh, my patients expect something that only a doctor can give them." And I don't think that that is actually true. I think where I hear the complaints is, “The doctor thought I was after a pill. I wanna feel well. I wanna get my health back. I want to recover.” 

And so that difference is the doctor thinks the expectation is what's the pill you're gonna give? We reach for a script pad or we reach for the name of a particular probiotic and we hand that over as though that's a solution without ever changing the environment. We've moved away from the Hippocratic concepts of the environment and the circumstances and the family and the units to the more Roman concept of “We will fix the problem that we see in front of us.”

And I...the balance has gotta be right. You do have to fix the sick person. You've gotta intervene in a way which has an evidence base to it where you can say, "Here's the likelihood of a good outcome." But if you don't fix the kind of structure around that, the family, the living, the stresses at work, then we will guarantee that the gut will go off. The gut seems to be far more sensitive to stress than almost any other organ. The gut, the brain and the heart together give really clear signals of when things are going wrong. We pay no attention to them. We're all fearing heart attacks but we don't fear gut attacks. When we put up with irritable bowel syndrome, it's a gut attack.

Andrew: Yeah.

Mark: It doesn't kill you but it makes life bloody miserable and curing that…

Andrew: It can near kill somebody. I’ve seen somebody with multiple hospitalisations. It wasn't a remedial disease at all. This lady was hospitalised multiple times for severe dehydration from IBS. So, you know, I caution practitioners out there. Don't trivialise irritable bowel syndrome.

Mark: No. In fact, now the gastroenterologists… so since that paper in Gastroenterology, I think it was two years ago or year and a half ago, which just took irritable bowel syndrome with diarrhoea and put...did the DQ2 and DQ8, did the genetic testing to find out who had the so called Coeliac genetics. This were not Coeliac patients. These were irritable bowel syndrome. And with the gluten free diet around about 70% to 80% of the people who responded to the gluten free diet, halved or more than halved their irritable bowel syndrome symptoms by simply coming off gluten.

Andrew: Just gluten, not FODMAP?

Mark: Just gluten. No, it was not FODMAP. This was a low gluten diet and the paper would simply say, "Well, we do know that there's something about the immunological response to gluten and to Coeliac disease." This is non-Coeliac disorder which we regard as a functional disorder where doctors use… where functional may mean “all in your mind and they're not really real.” But here was a really real thing that could be done. 

In a blinded trial, take people off their gluten versus those who didn't come off their gluten and look at the outcomes. Now these were severe IBS patients and it was not cure that was going on. It was relief of symptoms and a dramatic reduction in symptoms in those who came off the gluten component versus those that didn't.

So we still have a lot to learn and, you know, this is where I think Fasano and Pearlmutter next year are really going to be critical to making these distinctions. The broad brushstroke is take everyone off gluten. A lot of people get better. The doctors say, "But that's not Coeliac disease and the only thing gluten does is Coeliac disease." No. Thyroiditis for women in their 30s. Way more than half of the women that I see with thyroiditis carry the Coeliac genes and the thyroid antibodies drop with two things: adding selenium and getting them off gluten. And you can watch the antibodies drop exceptionally reliably with just those two tricks for the thyroiditis.

I have some sympathy with the guys who believe, "Well, it's DQ2 or 8." But there's something else about thyroiditis. And so one view is there's gotta be a Yersinia bug because there's mimicry between that and the thyroid and that's why we attack it. And that picture is yet to be worked out. 

Do you need a genetic susceptibility plus a grain plus a pathogen? And why doesn't everybody with the Coeliac genetics go on to develop these problems? But that's the fascinating area. If we know the susceptibilities, why challenge that? Why pick a fight that is unnecessary with a prolamin which is the component of gluten that the immune system just seems to get annoyed by?

Andrew: I haven't looked at it yet, but I just saw a link last night and I hope this is correct for our listeners but I think it's gastroenterology and herpetology, 2015, October and there's a link that's talking...I think the whole issue is dedicated to non-Coeliac gluten sensitivity. 

So it'll be very interesting to see the articles that are coming out now. And certainly, it will be really interesting to see, you know, the whole array of speakers that we have at the 2016 Symposium, BioCeuticals Symposium but in particular Dr. Alessio Fasano who is the discoverer of Zonulin. 

Mark: Yes.

Andrew: I mean, that's going to be really interesting to hear him talk.

Mark: Yes, and I think he, not singlehandedly, but he has done the majority of work in saying, "Here's the genes, here's the immunology, here's the reactions, here's the gastroenterological separation of the cells." It's been wonderful over the years just watching him put the jigsaw puzzle pieces together and now watching the gastroenterological specialty moving along in that direction saying, "Aha, that answers a lot of things that we did not understand before."

Now like everything, a pendulum will swing too far. Once the gastroenterologists get it, everyone will be gluten free. And then they'll say, "No, it didn't work. See, in a 100% of the population you can't get that.” But what I think we can do is always pay attention to the family history. Who in the family either has Coeliac disease or thyroiditis? 

The best question to ask to find out if someone is gluten reactive is, "Mother, grandmother, aunts, how many of them had thyroiditis or had thyroid disease?" And you get this answer of, "How would you know that my mother and grandmother and everyone had thyroid disease?" Well, because these genetics predispose women way more than men to getting a thyroiditis, where they go through their 20s hyperactive a bit, and they enter their 30s and the thyroid is now malfunctioning. High thyroid antibodies, inflammation. And now doctors focus on treating the thyroid instead of treating the gut. 

And get back to the gut and you watch the thyroid antibodies drop and thyroiditis is an imminently treatable disorder. Women now restore their thyroids by going through the diet and the probiotics managing the thyroid and they don't have them burned out. They don't have them damaged. They don't have them removed. They get back to functional thyroids about three to four years later.

Andrew: I had a book and it was by Thieme Publishers, T-H-I-E-M-E, and it was on thyroid disease and it was looking at the issue of tolerance. And yet they totally missed the input or the interplay with the gut. They spoke about tolerance but only from an immune cell perspective. Not how that immune cell was recruited in the gut. It was really interesting. They missed the game.

Just moving on there to a condition which affects many Australians, certainly with our modern day lifestyle. But also as an infectious agent, I think it's a Group 1 agent for carcinogenicity and it is purported to affect around 50% of the world's population at least some time in their lives and that's Helicobacter pylori which is said to be causative in about 95% of gastric ulcers, duodenal ulcers. So and this was obviously the discovery by professor Barry Marshall and Robin Warren over in Western Australia.

So Helicobacter pylori as a medical disease has been fraught with problems ever since the triple therapy was devised by Professor Tom Borody and that is that you get poor compliance because of side effects.

Mark: Yes.

Andrew: Talk to me about what happens in your clinic with the triple therapy and how you circumvent those side effects so that you get better results for your patients.

Mark: I'm still gonna be a heretic here, right? There is a move back away from Helicobacter as their cause in the medical community. What was demonstrated is that researchers in Western Australia who swallow capsules full...or liquid full of Helicobacter can in fact induce ulcers, which is true.

Andrew: Barry Marshall got gastritis, not an ulcer. Yeah, yeah, yeah.

Mark: Gastritis, okay. But the fact that there is inflammation is true. And I think there's some interesting research that says Helicobacter is an agent which in the right circumstances becomes pathogenic and inflammatory, but which can also exist in non-inflammatory states and may even be a probiotic which has beneficial effects.

Andrew: Yes, with hunger.

Mark: Yes. And so there may be a part to play. Every time we define something as a pathogen, it's like defining something as a weed.

Andrew: A weed, yes.

Mark: Yes. If you define a weed and Saint John's Wort is a weed. What's Saint John's Wort’s use? It can be a poison or it can be a therapeutic effect. I take Helicobacter patients and I have discussions with gastroenterologists, "Well, we can cure 95% with a single course of the triple therapy." And then I have these patients who come back over and over and the Helicobacter is there because the person is unwell. It becomes like most bugs, a different bug when things are wrong.

Andrew: Yeah.

Mark: So people have hypochlorhydria or hyperchlorhydria. People who are not eating well. The Helicobacter has a whole different life cycle where inflammation is occurring. Because with survival ability, it's able to stay there for long times. Anything which is an irritant on a mucosal surface will cause cancer eventually. It will cause ulceration earlier. 

So a mutagen plus a mitogen. Anything in the gut can be mutagenic because we have nitrosamines, we have all kinds of chemicals coming through in our food. It's a highly reactive environment. Lots of hydrochloric acid. And you get really dangerous molecules around there that requires an excellent mucosal protection. It requires a very deep ability to control this explosion of acids and nitrites and everything else, and when it breaks down through diet or lifestyle, the bugs are always there and now become pathogenic in that area of the gut. So I do think that there's a place for triple therapy in a person who has developed a Helicobacter infection where you want quick control. 

You're right about the seven day course of treatment giving a lot of adverse effects. And if the goal is, "We just wanna get this better. We've gotta get the ulcer out of the way." I think that there's a value to doing the seven day treatment as a first line of treatment in a medical treatment. But I think there's a way bigger issue of maintaining gut ecology in the upper gastrointestinal tract, determining if a person has low or high hydrochloric acid as their baseline. If so, why? And I think that we also need to respect that the gastrointestinal tract, even the stomach needs to be respected as a place where you do the second stage of digestion. Saliva in the mouth and chewing. The next stage is you've gotta have your acid, you've gotta have your mucosal protection and re-establishing mucosal protection on the stomach wall is a different business to re-establishing it on say, the ileum or the jejunum or anywhere like that.

So I think our simplistic view of “There is a bug, there's the ulcers. It must be cause and effect,” ignores the fact that the bug is there and becomes pathogenic for a reason and is non-pathogenic in a huge number of people. If you do the Helicobacter serology and the breath test, you find many asymptomatic people who also have breath test positive and serology positive. Are they at war with it? Well, not symptomatically. Do you treat it? We actually don't know. 

What we do know is if you've got gastritis and you've got ulceration, you have a short-term medical problem you have to stop progressing. And there is value to the antibiotics in those circumstances. Do you leave it there? Not at all. Because the relapsing rate for those people...the bug will return.

Andrew: It will return anyway. It's very hard to eradicate.

Mark: Yeah. And you have to be at peace with that bug. You need to develop a relationship with your Helicobacter where it goes back to whatever its mysterious role may be. 

It reminds me a lot of, you know, do we introduce parasites into people for control of other inflammatory disorders? Do you treat Coeliac with, you know, parasites? Do you treat allergy with parasites? So there's a lot of stuff going on on the gut wall that Helicobacter sits as a headline because doctors thought, "Oh, we always thought it was stress and hospitalisation." Old Doug Piper over at North Shore was one of my teachers and it was all people in hospital for seven days and they get better from their ulcers. That all got wiped out by the Helicobacter story, and as I said before, the pendulum swing goes so far that you think that the bug is the only reason for ulcers or for gastritis. 

Andrew: Yes, that’s right.

Mark: Swings back the other way and we'll have to find our middle ground there where peace with Helicobacter is what we're after. We are not after a war that we can never win.

Andrew: Yeah, and I might point out for our listeners that the big problem with triple therapy and the subsequent quadruple therapy if they need it, is compliance. Because people feel so rotten on that therapy that they very often stop. I think it was somewhere around 30% of people actually don't finish the therapy. Therefore, that therapy can't have the beneficial effects on "eradicating" Helicobacter pylori. You'll never eradicate it. And therefore, the condition persists.

There's good evidence to show that Saccharomyces boulardii, lactoferrin and something that's just now available on the Australian market, the zinc-carnosine, a combination of zinc and L-carnosine together. They have evidence on reducing the symptoms of triple therapy so that people can stay on the triple therapy to its entirety, and therefore get the beneficial effect of the eradication of the organism. 

So it's a really interesting thing. The zinc-carnosine actually has some very interesting attributes as well, but it actively heals the ulcer. The zinc basically gets absorbed into the inflamed tissue allowing the carnosine to heal, to stay in the localised area and heal the inflamed tissue. So it's really interesting what's happening.

I think the lesson is to be able to give something to patients whereby they can add it to their medical therapy and get a better effect. Indeed, what doctors should be investigating there so that they get better results in their patients.

Mark: Yeah, get in, get out, do the job that you wanna do, and make sure the person is minimally adversely affected by that intervention. That's exactly what… pinpointing your target, winning the battle and getting out, getting on with maintaining health and gastrointestinal health. Those are great goals. 

So anything that can be done, and this gets back to that idea that there's plenty of nutraceuticals that if administered with drug therapy absolutely diminish the symptoms and allow the drug therapy to work better which is why every doctor should be integrative because it improves orthodox medical care. This is not weird. This is simply, we know things. We know stuff with micronutrient loss with antihypertensives, with anything that you treat the gut with, there are costs to it. And if we are able to ameliorate the costs and the difficulties that the person goes through, compliance goes up. If compliance goes up, you win your battle quicker.

Andrew: Absolutely. Indeed. You know, I'd like to say I don't understand why doctors are so adverse to integrative therapies automatically, but in fact I do understand it because I was one of them. Like not one of them but as a registered nurse, I was that medically aligned model. I was so medically aligned that I used to denigrate and relegate any natural therapy that would've been proposed to me, regardless of the evidence. And all I would implore orthodox GPs is to just look at the evidence, and then heal your patients and think of your patients.

Mark: And remember, we doctors like quick results. You know, intervention, the Roman model is rubor, dolor, calor, tumor, that if you can see something, hold it and you can see the pathology and you can aim your rocket at it, it's a very impressive profession to see that rocket hit its target.

Andrew: Yeah.

Mark: Is that the end of the story? No. It's the beginning of a story where you've rescued a person from an edge. What do you do as act two? And act two is increasingly being taken up by the integrative doctors whereas orthodox doctors should know this information. 

How do you get the person not just back from the edge but restore health, put the gate up and make sure they're not falling over again? Weirdly, the medical model is, “If they fall over again, I can treat them next time, I can treat them next time." And so I think that there's a business model to medicine which says there's no downside to not preventing in the future. In fact, that's the business of medicine is to keep that rescue going.

That's the old metaphor of “We put ambulances at the base of the cliff.”

Andrew: I love this.

Mark: We don't build the fences at the top. And the fences at the top are what we're talking about today.

Andrew: Yeah.

Mark: The gut is one of those walls that people fall through very, very swiftly. And they keep landing with thyroiditis, autoimmune, inflamed joints. They end up with migraine headaches. There's a whole plethora of medical disease states that come from a common background of causes. 

I have a battle at the moment, and I know this from the gastroenterologist. If a person says they have a leaky gut, never believe them because that's a naturopath that said it. If they say, "I've got increased gastrointestinal permeability,” that's a medical diagnosis. 

When you have lay terms for something, doctors get weird, the hairs stand up on the back of our neck. They go, "I'm the one who decides if you have that." But we've gotta be willing to let that go. Better educated people come along and they've heard about leaky gut and they have heard about Coeliac genetics and a better educated population needs doctors to go that extra step to say, "I understand that, and I will work with you on that. Let's fix the medical problems. Now let's get on with the job of restoring your health." And the other group, your family's health. 

Because things that are genetically susceptible like Coeliac genetics...the number of doctors who find them in the adult...have never mentioned that the kids are going to probably have some of that and have you wondered why your child may have autism spectrum disorder, hyperactivity? Why not think that there's a possible changeover that we need to think about the broader family and how to it affects children, grandchildren or even parents. So this is one where the target patient appears. You identify the problem. You make sense of the generation before and you give the opportunity for the next generation to not run into those problems.

Andrew: That's actually a very salient point because Helicobacter pylori is transmitted vertically i.e. mother to child. So that's where the vector, if you like, is. It's not gotten from some infectious agent that you came in contact with on a cruise or something. 

Mark: No one coughed on you.

Andrew: No one coughed on you. It was yours. We just gave it the right environment for it to proliferate. So if that doesn't change, you're going to get it again.

Mark, let's move on to something that...you know, we're talking about the serious gastrointestinal inflammatory disorders now, right. The inflammatory bowel disorders, the ulcerative colitis, the Crohn's. The medical use of probiotics and indeed, something that’s, I would say it's cutting edge but it's really starting to be a groundswell here and that's the application of faecal transplantation, which is to me something so exciting. Talk to me about the application of firstly, probiotics and diet and what happens in the treatment of these patients with anything from an aspirin derivative to chemotherapeutic agents to faecal transplantation.

Mark: I have experience of both. The faecal transplantation is not the most popular thing in the world but it is gaining a reputation. We're just getting people around the yuck factor and the idea that we may have oral agents we are effectively swallowing...I won't even use the word. But that disgusts some people but at its core, this is Digby eating possum poo. Getting bugs in is more art than science right at the moment. 

What we do know is that we can intervene in Crohn's disease and ulcerative colitis reasonably easily. With sufficiently high dose probiotics, with Saccharomyces we can do things on the gut wall that make a difference. There is even some evidence of things like glucosamine and the ability to put in the glycans so that these bugs have an opportunity for inflammation control at the site on the gut, and more broadly throughout the body.

I think of these inflammatory disorders in a way that's very different from a gastroenterologist. They see it as, "Let's use something which heals the lesion and minimises the damage." Which is not a bad goal. But sometimes it's at odds with getting good gastrointestinal function back. When you have drugs that break up into a steroid and an antibiotic and you're getting that dual effect, it's hard to imagine the gastrointestinal tract maintaining a reasonable balance even though the symptoms of the disease are increased.

And I know that there are controversies arising and the evidence for Crohn's is a little bit weaker than it is for ulcerative colitis but I think even the orthodox gastroenterological specialist area of medicine is moving into the probiotic era for the management of both of those conditions. Their review recently of evidence for ulcerative colitis management is pretty strong. And the fact that there's a microbiome project looking at, “Could we strengthen that even more? Could we refine what we're offering here?” 

But at the simplest level, the Saccharomyces and the high dose probiotics, the high dose Lactobacilli and Bifidobacteria are reasonably straightforward ways of trying to make a difference to re-inoculation of the gut. The dietary approaches I think, are also important and I know the gastroenterologists often bristle with this. You know, "Don't put my patient on diets. I've got them nicely controlled with the drug therapy." The question to the gastroenterologist should always be, "What's the long-term goal here? What are we trying to establish?" Trying to establish normal immunology in an area of inflamed gut is not easy.

So symptomatic treatment with the drugs that are used is a very valuable step one. Restoration of gut flora, microbiology and gut immunology is, in fact, you’ll remember from our last symposium, it is an enormously difficult task that requires a lot more research to be sure of.

My experience though with Crohn's disease and ulcerative colitis is that they are both recoverable conditions if we don't rely simply on symptomatic treatment.

Andrew: Yeah.

Mark: The combination of diet and probiotics works slowly. Progressively, you see the C reactive protein numbers come down, the ESR numbers. They're just general markers of, "Is inflammation going on down there?” The carcinoembryonic antigen is another marker. 

So as doctors, we can watch what our interventions do as long as we're prepared to have a look over a period of say, a month to two months to six months. There's really straightforward ways of saying, “How is that gut doing?” And when you see the carcinoembryonic antigen, the CEA numbers dropping down progressively, and the C-reactive protein dropping and the person complaining of less symptoms, it's a very, very powerful process. They are encouraged to go back and look at what they can control in their own diet. The relaxation is important and getting congruent with gut and living foods, I think that that's where most of them need to actually end up.

Andrew: I had a young lady...I have a young lady who I'm treating who has Crohn's disease and the antecedent for that was severe and emotional upset at a period of time in her life. A young 20-something. And she also embarked on a high dose oral contraceptive pill.

Mark: Yeah.

Andrew: And the interesting thing was, as well as rather aggressive medical therapy at the time, one of the biggest changes that she found was coming off the high dose onto a low dose oral contraceptive pill. So maybe something is seemingly distant as changing the hormonal profile which has effects on inflammation in the...

Mark: Yeah. Yeah, and look, I've said this many times. A century ago, the whole thing was control of infection. Now it's control of inflammation. 

The better we do with inflammation control, the better we do with the chronic degenerative grumbling low-grade diseases. We're good at medicine at stopping the acute exacerbations. What we lack is a strategy that is a lifelong strategy which allows the person to regain their health. And we think of, you know, extend the medical treatment lifelong. It doesn't work out very well. That just distorts more and more of the gut immunology and other problems arise over time. So it's a difficult area. 

Ulcerative colitis, Crohn's disease, Coeliac disease, as well. They're owned by the gastroenterologists. So the gastroenterologists have to be the ones to come around because they are potentially serious disorders. Crohn's disease almost universally has the problem of low vitamin B12. And so that last part of the small intestine is critical to absorption of B12. And the number of times we forget that the Crohn's person, even though symptomatically controlled, is just destroying their ability to absorb B12 at distal ileum.

Andrew: Indeed not just B12 but all of the fat soluble vitamins as well. So for instance, I mean, vitamin D was the hero for everything. And some of the trials, the intervention trials haven't been as shiny as the results that we'd like but autoimmune disease? Man. There's a real use for vitamin D there.

Mark: Yeah, and that link between gut and autoimmunity, very, very, very strong one.

Andrew: Absolutely.

Mark: Nearly all of the really useful research is going on to what do you do on the gut to manage the general immune response. It's not trivial. I remember many years ago a very well-known professor and I sat down in a room and he said, "Mark, your problem is you think the gastrointestinal tract and the immune system are linked. This is why we have specialties. There's nothing about immunology in the gut and there's nothing about gut in immunology. It's just where the cells happened to be." And I think now that position will be regarded as absurd.

Andrew: Yeah.

Mark: But if you manage the gut, the immunology, this whole process of autoimmune thyroid disease, autoimmune ovarian disease, lots of infertility, things not obviously related to the gut are intimately related to the gut. And management of inflammation via the gut is a vastly important area of my profession's approach to inflammation. 

We're always looking for the next drug that will have no side effects but control inflammation. It sits in front of us and it's called diet and it's called gastrointestinal microbiome and they do a fabulous job if we support them. It's not drug intervention as such, but the drug intervention is useful only for the initial stages.

Andrew: So Mark, we've spoken about gut conditions anywhere from Helicobacter, irritable bowel, right through to the really severe ones, the ulcerative colitis, the inflammatory bowel diseases. Can you give our listeners a wrap-up as to when to use probiotics and what other factors you use, what other things you use in combination with them to get better efficacy?

Mark: I would like to start with something that I failed to mention which is get sugar out of the diet. I mean, in all of these areas our reliance on sugars, our obsession with going low fat and jumping up all the sugars, those disaccharides, monosaccharides have made a huge difference to the dominant organisms of our gut. 

Andrew: Yes.

Mark: Breaking sugar addiction is a critical part of getting a person on the road back to good gastrointestinal health whether we're talking UC, ulcerative colitis, Crohn's or irritable bowel. It's equally important at all fronts. And people resist it, and it's really hard with teenagers and it's really hard with people who become so used to sugar that they can't imagine a diet without it.

So sugar out. A trial of getting people off their grains. Principally, wheat, rye and barley for the gluten components of those grains is always a really good start. And my approach to any of these disorders of chronic inflammation, especially gastrointestinal symptomatology is it's always worth a trial off gluten, off sugars, of milk products. Watch the first month like a hawk and find out what the gains and the losses are.

So to me, that early intervention is start that process. If I can get people interested in looking at living foods and fermented foods, I encourage them along those lines as well. They will try them out and they'll adopt them themselves. But primarily, it's getting people interested in cooking, sitting down with their family, eating and turning food back into that pleasurable experience that we want.

Sometimes my job is to break the diets that others have said, "You must stay on for the rest of your life. You must be on an anti-candida diet. You must be on this." No one has to be on one diet all their lives. Because we are adapted to fresh foods in season, we ate what we got. There's a value to a starvation bit of winter, which we never have. We go for more food in winter rather than less. And there's a value to the fruits and vegetables in season. There's no right diet for everybody nor even for an individual over time. So that's the groundwork to me.

When I've got a specific target, my choice is generally the high dose probiotics of the Lactobacilli and the Bifidobacteria groups and a reasonable dose of Saccharomyces boulardii. If they're on antibiotics, the probiotics are difficult because they will be murdered by them and you have to separate them, you know, do the 12 hours. But many antibiotics are four times a day so it's really hard. And the rule there is leave the probiotics till the end. Keep the Saccharomyces going because they can moderate that gut immunology and interleukins there. And then get on to the heavy doses of probiotics immediately after.

I'd also draw a distinction. There are people who need short-term antibiotics and need short-term probiotics to re-establish things afterwards. But for people who have been on six months of antibiotics for chronic cystitis, your arthritis, acne, lots of those things. After six months of antibiotics, it's no longer a two, three, four week treatment. You have to work hard with all of these tools at your disposal. Antibiotics have value but the cost of them long term...people experience the upside when they take them short-term and then they experience the long-term adverse effects for 25 years afterwards. So that work and going back into history and saying, "Did you have long-term antibiotic use?" And recognising that as a risk factor for gastrointestinal disease and inflammatory diseases is critical.

So those are, to me, the goals. You've taught me something new today with the management of Helicobacter treatment. So I did not know that we couldn't ameliorate those symptoms. I've always run into the patients who have severe symptomatology from the attempt of treatment, failed treatment time after time. And so that idea of the zinc-carnosine and the Saccharomyces, and what’s the third component?

Andrew: Lactoferrin.

Mark: The lactoferrin. So knowing all about those individually, that's a...sounds to be a very good combination for effective initial treatment, minimise the symptoms and then restore gastrointestinal function and pay attention to stomach acidity for organs.

Andrew: One of the problems that patients have is that, “You've now told me to get off sugar. Well, what do I do? I've got this craving for sugar. How do I manage that?” And I think practitioners can learn something from… you know, if you wanted to say paleo, do that but the problem with saying paleo is people think automatically high meat.

Mark: Yes.

Andrew: Whereas Lauren Cordain and Pete Evans actually made a paleo diet for our 2013 Symposium and it was mainly vegetable matter.

Mark: It was. And it was fantastic.

Andrew: And it was fantastic. But the trick is, that you replace sugar with good fats. And you can get them from a number of sources. They don't have to be animal. You can get them from good plant sources. But that's the way that you ameliorate that up and down, the sugar craving. The other thing is the use of MCTs, medium-chain triglycerides.

Mark: Yes. They’re useful. And you remember, I mean, the sugar industry thrived on the low fat concept. What did you replace fats with? You replaced it with sugars and people couldn't tell the difference. So finding now...fat was evil. Now we're far, far more subtle about that. There are good fats, there are therapeutic fats, there are caloric fats. And being wise in the choice of the fats that we consume is now a very, very big thing. 

Do we do that for our diet 24 hours a day, 7 days a week, 52 weeks? No. You do not need high fat diets. There is beautiful fruit that can be in season and you can go for those sugars. Depending on how you go with fructose, generally. I tend to get people off fruit juices as well. 

Andrew: Yes.

Mark: That typical problem of if fruit is good for you, well, 12 of them in a juice that I can scoff down before I go to work must be even better. And that is not food. That is not something that we evolved to be able to take. But eating fresh fruit in season is one of those joys that makes eating worthwhile.

Andrew: But interestingly on this Crohn's patient that I'm treating. If you gave her...like she can handle a ripe, soft banana. Half of a banana. She can't handle apples.

Mark: Yeah.

Andrew: But berries are fine. However, she finds for a...call it a sweet treats. Not really, but she juices vegetables and she actually gets the taste right by having some vegetables. Not too much sugar but a little bit of that...you know, call it a sweetness, if you like.

Mark: You can add...you know, at the biochemical level and the energy level, you can add the medium-chain triglycerides to give that little bit of a boost that people feel improved in their mitochondria function at a higher level. And so they get the benefits that they've always associated with sugars through a better metabolic process, or a more diverse metabolic process that does not have, you know, the glycosylation end products that the sugars are going to have and it does not feed the gut bugs that we are trying to keep under some control to minimise inflammation.

Andrew: And it's actually a nice oil to take. You can make it into a salad dressing. So it's actually something you can really easily incorporate, this MCT oil. It's actually...

Mark: People...when you hear...when I tell them about it, they say, "Oh, that'll be disgusting. Heavy oil." It's not at all. 

Andrew: No, not it’s not.

Mark: Medium-chain triglycerides are not slabs of fat that you push down though…

Andrew: Slabs of lard. And on that note… Dr. Mark Donohoe, thank you so much once again. You know, your patients must love you because you… Obviously, by the time they get to see you, they've been through the wringer so they're the people who are unwell and chronically so. 

But I love the way that you take time to go into not just the symptoms that are presenting, the little box of symptoms but the antecedents, the whys and wherefores, how did you get here and that is probably why these people seek you out to get long-term treatment options. So I really applaud you as I always do, but I really do applaud you for what you give back to the community.

Mark: Nice of you to say so, but I think a lot of it is if you listen to the person's story, they tell you the reason that they're sick. They even often have the answer that no one's listened to. And so time for a practitioner is the critical factor to complex issues like gut disorders. There's always a reason. And sometimes it's the family history, sometimes it's in the dietary history, sometimes it's elsewhere. But if you listen, I'm amazed at how often people intuitively know where the problem arises and will tell you the answer. It's just a beautiful part of medicine that if you listen, you will learn and they tell you what you are going to tell them right back.

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



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