Microbiome Medics

The Microbiome, Dopamine, and Parkinson’s: Exploring the Connection with Martha Carlin

• Season 1 • Episode 23

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In this episode of the Microbiome Medics Podcast, Dr. Sheena Fraser is joined by citizen scientist Martha Carlin, who shares her personal journey into the world of Parkinson’s disease research. After her husband John was diagnosed in 2002, Martha utilized her background in accounting and systems analysis to investigate the complex connections between the gut microbiome and Parkinson’s symptoms. She emphasizes the role of dietary changes, including organic foods, and discusses the innovative probiotic formula, “Sugar Shift,” developed by her team that showed promise in enhancing gut health and alleviating symptoms.

The conversation explores the gut-brain axis, detailing how gut health affects neurotransmitter production, notably dopamine. Martha advocates for a holistic approach to treatment that includes lifestyle modifications such as exercise, which greatly benefited John. Reflecting on her husband’s fight against the disease and their quest for awareness, Martha encourages listeners to advocate for further research into Parkinson’s and consider the microbiome’s role in chronic disease management.

Links:
www.biotiquest.com 
www.marthasquest.com
www.thebiocollective.com

This podcast is brought to you in collaboration with the British Society of Lifestyle Medicine.

Disclaimer:
The content in this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your doctor or qualified healthcare provider. Never disregard professional medical advice or delay in seeking it because of something you have heard on this podcast.

Intro and Outro:

Hello and welcome to the Microbiome Medics Podcast. I'm Dr. Siobhan McCormack. And I'm Dr. Sheena Fraser, and we're your co-hosts. We are both GPs and lifestyle medics with a shared passion for microbiome science, and we have spent the last five years deep diving into the world of the gut microbiome. We'll be translating the evidence and packaging it into actionable, bite-sized chunks so that you could harness the power of the microbiome to improve your own health and that of your patients. Just before we start this interview, we'd like to remind our listeners to take a look at the Gut Microbiome for Clinicians course. It's available through bslm.org.uk. It's a comprehensive course on the gut microbiome, which takes you from the basics to the clinical application of this fascinating new area of medicine. This course will empower you to use microbiome science in your daily practice.

Sheena:

Hello and welcome to the Microbiomedics podcast. I'm Dr Sheena Fraser. Today I'm here with Martha Carlin. Now Martha describes herself as a citizen scientist. She's on a mission to find a cure for Parkinson's disease. Parkinson's is a degenerative neurological condition which is absolutely devastating. Her husband John was diagnosed with this condition in 2002 and Martha went on her journey then. So I'm going to let Martha tell you all about this journey. It's a really interesting one and it'll allow us to really go into the gut-brain axis and the relationship between conditions like Parkinson's and the microbiome, which is a really interesting area. So Martha, welcome to the podcast.

Guest:

Thank you so much, Sheena. I'm excited to be here.

Sheena:

Well, Martha, just kick us off. Tell us about the start of your journey. So tell us what happened in 2002 and why you've ended up where you've ended up. And let's just go through the history.

Guest:

Sure. So in 2002, so John and I were a young married couple. We had two small children, And then I had an older child from another marriage. And he was a marathon runner, really athletic, seemingly healthy, never really had any kind of health issues that we thought. And in November of 2002, well, earlier that year, I noticed that he had a little tremor in his pinky and a little tremor in his tongue. And that was about the time that Michael J. Fox's book, I think it was Lucky Man, the first one that he wrote. Came out and I was reading that and looking at the symptoms he was talking about. And I was like, you know, I'm seeing some signs of this. And John was also, didn't have the same kind of facial expression. Or when he looked at me, his pupils didn't dilate the way they normally did. So, you know, I didn't tell him what my suspicion was. But, you know, I suggested he go to our internist and, you know, he went there and brought me with him for the evaluation after all the testing and everything. And the doctor was like, oh, you look great. All your blood works great, you know, blah, blah, blah. And I looked at the doctor and I was like, well, what about his loss of facial expression? And what about the tremor? And I could see this look of recognition on the doctor's face. Of course, you know, here, a doctor only sees you for 15 minutes, maybe, if you're lucky. This doctor, a little bit longer. But still, they don't see you often enough to really see those kind of subtle changes. And so he said, I think maybe you need to go see a neurologist. And we went to the neurologist. And just from watching John walk down the hall, the neurologist knew it was Parkinson's. And after a very short examination, you know, he looked over at me and he said, you know what I'm going to say, don't you? And, you know, I said, well, probably. And then it's this... You know, they give you this diagnosis with a terrible outlook and prognosis and maybe a couple of books to educate you, which aren't very helpful. And I had always been a problem solver. I had worked, my background was in, my undergraduate training was in accounting, which is a system that has to balance. And I had gone on to be trained in auditing, which is never take anything that somebody tells you at face value, examine the evidence for yourself, and then trained in this systems-based approach of how to look at business risk. And so I came out of there just, you know, gunning for action of, okay, I've got to examine the evidence for myself. I've got to look at this from a systems perspective and what's flowing through the system. And so I first started to look at the food because that's the main thing flowing through the system. And I went home and tossed everything out of the cabinets and decided that we needed to go all organic. But in 2002, there was very little organic food. So that really launched my scientific journey on the food side of things to understand what had happened to our food supply, what we had done in terms of engineering crops, of processed foods, of chemicals, because so many of the chemicals that are used in agriculture were actually neurological weapons in World War II that got converted. And, you know, just from a logical standpoint, you ask yourself, like, why would you spray poison on your food? It's kind of nuts. And so that journey went on as I and I would progressively look into different connections to Parkinson's and ultimately started looking at. The deeper literature in Parkinson's. But in 2014, so that's, you know, quite a few years later. I read the first, well, I read Martin Blazer's book called Missing Microbes. And over the years, I had interviewed, when I would meet somebody with Parkinson's, either at a support group or just out, I would kind of do a little interview. What's your life story? What do you think contributed to your Parkinson's? You know, have you, did you have this? I started to see these patterns and that's kind of one of my things is I see patterns. And Martin Blazer's book was about the age of antibiotics that we've all been raised in and how that was connected to the rise in chronic disease. He didn't have Parkinson's per se as a focus, but a lot of these other chronic diseases. And I knew from interviewing people with Parkinson's that many of them had had repeated strep infections as children. And so they'd taken many courses of antibiotics for that. And so, and I had never heard the term microbiome. So that just launched me into this amazing world of the microbiome and teaching myself. And, you know, 2014 was an amazing time because both the European Microbiome Project was publishing a lot of their research and the Human Microbiome Project here in the States was publishing all this stuff. And there weren't that many, quote, experts. So if you studied, you could kind of catch up. And later that year, the first paper was published by Dr. Philip Sheperhans that showed in Parkinson's. There are two primary types of Parkinson's. The one most people are familiar with is the tremor dominant, where you see the tremor in the hand and the shaking. The other one is called posture and gait, and that's where they're stooped over and have trouble walking, have a shuffle or freezing gait. And Dr. Sheprahans was able to divide that by the microbiome data. They had two very different microbiome profiles. And I was like, Eureka! That's it. It's like the general ledger of the body. That's where it keeps track. And so I actually quit my job and started funding research at the University of Chicago with Dr. Jack Gilbert, who's kind of one of the stars of the microbiome field.

Sheena:

Yeah. I was actually in a meeting with Jack Gilbert a few weeks ago. He's a nice guy.

Guest:

He's very charming and very, very knowledgeable and really open-minded. And in that early work with Jack, we started talking about he has a son with autism, and there's some overlap in the microbiome data of autism and Parkinson's. And then I had been introduced to another woman who had spent about 20 years at the CDC studying chronic fatigue, and there were some overlaps in the microbiome there, and. We said, well, you know, what's really holding back the research? And it was really access to quality samples because there's so much bias in all of these scientific processes. And that was something Suzanne from the CDC knew a lot about from doing these large-scale population studies where she'd have to throw out samples that weren't properly collected and stuff. So we came up with this concept for the BioCollective where we would collect a big bank of fecal samples and make that available for researchers around the world to do early research. And we hoped that they would share data, but that didn't quite turn out to be the case. And we were a bit ahead of our time, but we started this project. And, of course, with my Parkinson's interest and connections in the Parkinson's field, I had access to a larger group of people with Parkinson's. And so we started collecting the Parkinson's samples very early on. But we collected just over 1,000 people of healthy, different disease profiles. And we did whole genome sequencing and started to compare and look at that data and make our samples available. And so our Parkinson's samples, actually, some of those went to University College Cork in Ireland to do work on the virome. We did a study with Sarkis Masmanian and one of his postdocs at Caltech. We did a lot of our own work. Really kind of pinpointing and looking for specific things, using some different techniques than what are typically used. And the young women in our lab who were processing the samples as they came in had this incredible observation that had never been published in the literature. So people with Parkinson's report constipation, about 70 to 80 percent, report constipation as an issue. And I think physicians don't really understand what they mean by that. And some of them might not even go, but once a week. And the girls in the lab could, or I should say women, that's probably, anyway, they were a lot younger than me. The women in the lab could tell if a person had Parkinson's just by looking at the stool. It was different from every other stool that came through. And it had a consistency like concrete. And this made it so most of our samples we processed using a syringe. We could not do that with Parkinson's. We actually had to use a caulk gun because of the density and, colloidal structure of the stool. And so, you know, this was like a huge insight, which has translated all these many years later to some research I'm doing with an Australian scientist who's a colloidal chemist who has kind of figured out what's going on in the microbiome. So that's like a very long thread into the story. And there's a lot more from there, but maybe I'll stop it there and.

Sheena:

Yeah gosh I mean that's the first time I've ever heard that about the you know the structure of the stool um as a as a medic you know I know that people who suffer from Parkinson's disease have decades of constipation before their diagnosis um and that is one of the hallmarks of you know that that risk um that seems to transfer to to developing Parkinson's but I had never heard about that. I mean, I guess, as you say, you know, how many of these patients are we actually collecting stool samples and considering that? And maybe that hasn't been noted because, you know, we don't know what it means to have stool that density. We just don't know what that means to the rest of them or, you know, whether that actually translates to any other issues with the gut. Because, I mean, I think even gastroenterologists, although they have like stool charts to discuss different types of stools that people have, I don't recall that being on a stool chart.

Guest:

So I would say the Bristol stool chart, after kind of becoming the poop queen, our expertise, the Bristol stool chart is helpful, but it doesn't have enough detail. But what I would say is from learning that, then talking to people with Parkinson's about it quickly. I've learned even more. So that density, the stool will often be quite large in diameter. So if you think about the body's holding it in because it's quite painful to pass a stool that is that large. But with the work with Dr. Nenum in Australia, what we started, what he hypothesized and started looking at is these gram-negative bacteria, which we know are present in Parkinson's from a number of the studies, actually produce an enzyme called urease. And that urease then kills the good bacteria that spill out their calcium and potassium. And that calcium and potassium is what makes that concrete-like colloidal structure, makes it difficult for the person to access the nutrients. So you lose that accessibility to the nutrients and makes it difficult to pass. But you can actually, a very simple thing you can do to change whether those bacteria produce urease, and we did this with my husband, John. Was to put an ice pack on the stomach when you're eating, and it lowers the temperature just enough in that local area that those gram-negative bacteria don't produce urease. They produce urea and something else. I don't remember off the top of my head. So you don't get the urease that's killing the beneficial microbes. And those beneficial microbes are the ones that are making the B vitamins, the hormones, neurotransmitters, all of those things that you really need. And then, of course, if you have that colloidal mass sitting there, you also have a lot of what are called bacterial protein toxins. And, you know, there are many toxins that are produced by bacteria with different mechanisms of action. And so then the body's got to deal with that waste sitting inside the body and try to clear those toxins. And one of the best ways to clear the toxin is, of course, to pass the stool. And if you aren't passing the stool, then you're just repeating the cycle over and over.

Sheena:

Yeah. So, Martha, do we have any insights into how long before the diagnosis of Parkinson's you would develop those type of stools? Because presumably that's not lifelong. Presumably that happens, you know, a decade or two before, or is it just very, very gradual? Do we know?

Guest:

We don't know. But one thing I will say just from my husband's history, and, you know, often people don't know their history back this far, but he actually had constipation as a baby and a young child. And there was a memory of essentially his mother trying to bribe him with stuffed animals to go number two. And so I think it can go all the way back that far. But you really can't know without... Looking at a whole stool, I mean, for a researcher or a physician. And most of the stool testing is actually not getting the whole stool. You know, they send people home with a scoop or, and of course, then if they're going to scoop, they're going to scoop the part of the stool that's easier to scoop than the actual dense colloidal mass, which makes, brings about some bias there too. And just the process of collecting whole stools, you know, we spent a lot of time figuring out how to do that well and maintain a quality sample. But, you know, it's difficult. And in hospitals, they're not really set up to do that either. So, you know, I think that's an area to be explored further for sure.

Sheena:

Absolutely. And a really interesting observation. constipation and presumably your husband tried many things for his constipation because a lot of people would say, well, if you're constipated, just, you know, manage your constipation. Is it with people that have this level of constipation, is it very difficult? Does it not respond well to treatments? What was his experience?

Guest:

Well, you know, it was interesting because Because I think because he had had lifelong constipation, he never really thought of it as abnormal. And I think that's the case initially with a lot of people until it gets more severe. And then as it gets more severe, it's like, oh, okay, this is a problem. And so we really started to focus on the importance of having a bowel movement every day. And but a lot of sort of the typical answer at least here in the states is you know here take some miralax well you know that can be a short-term solution but there is microbiome research showing that that has a pretty significant impact on the microbiome overall and most of these laxative type things will have an impact on the microbiome and can also make it more difficult for you, to have a bowel movement without help. So, you know, it's a difficult challenge to address. I mean, you've got to do something to get the waist moving. So we tried, you know, Periodically, we would rotate. He used senna, magnesium oxide, which is a little bit more gentle. Yeah. Castor oil on occasion, you know, with warm water. But he did try to avoid Miralax and things like that. And we did add some fibers, but you have to be really careful that you are drinking enough fluid if you add those fibers or you can actually make it worse. And so it's, can be a bit tricky.

Sheena:

So did you notice, obviously this was all sort of post-diagnosis of his Parkinson's, and with the improvement in his gut function, did you notice any improvement in his Parkinson's symptoms? Because you would think that reducing down the toxins, allowing the stools to move a little bit more frequently will stop the buildup of those toxins and might reduce inflammation in the gut. What did you find?

Guest:

Well, so about, let's see, I founded the company in 2015. In 2016, I went to the World Parkinson's Congress, and there was a group from Israel called Clinic Crowd that was presenting a study from a scientist there who had shown that the sugar alcohol mannitol could actually stop the aggregation of the protein and pull them out of the brain of the animal and clear them. And I was like, wow, this is really interesting. And at that time, John was having trouble navigating a crowd and walking with a cane. And I came back and bought this little mannitol chemistry book and started reading about mannitol. And I was like, wow, what an amazing molecule. It's a powerful free radical scavenger. It's used a lot of times to help with drug delivery across the blood-brain barrier. It's also used to bring swelling out of the brain and traumatic brain injury. And it's used for thermal energy storage. It's part of the circuit prime for the heart-lung transplant machine. So there were all these interesting things about how it was involved in energy and transport in the body. But the first chapter of the book. Talked about the microbes that actually ferment mannitol from glucose and fructose. And I was like, Eureka, again. And I had a friend who was a fermentation chemist, and I said, could we make a team of microbes that would actually put this function back into the gut? And so we made this probiotic formula just for John to start with. And within 30 days of taking it, if we were measuring his microbiome along the way, we could see the improvement in the microbiome profile, the pathogens dropping, the beneficial microbes rising, and he stopped walking with a cane. And his Parkinson's UPDR score improved from a 35 down to a 20 over the course of a year. And then it stabilized at 20 for about four years until he had COVID. So, you know, there are definitely ways to modulate the microbiome. And it's, you know, that's certainly not going to be a cure. But I think as we see, the Parkinson's microbiome research has escalated dramatically. And I just did an update review for 2024 of the publications that have come out this past year and 296 peer-reviewed publications on Parkinson's and the microbiome. So, I think, you know, there's fecal transplant research that they're doing, studies in that area. They're looking at targeted therapeutics. And there were actually two fecal transplant studies, one in Finland with Dr. Sheperhans, that came from the bottom up and it was not successful. And there was one, I think, in Belgium. And they came from the top down and that one was successful. So I think in my kind of view of the things that I've been looking at is the top down is probably more beneficial because some of these microbes we're talking about that make the urease are actually colonizing the small bowel and you may have small intestinal bacterial overgrowth and that you need to address it in the upper GI tract instead of solely in the colon.

Sheena:

That's interesting. And I think, I mean, as she was chatting to Jack Gilbert about this a couple of weeks ago, we were talking about the reason why FMT is not effective in so many autoimmune conditions and other chronic diseases. And I'm in my other life, I'm a lifestyle medic. And one of the things that I think is really important is that if you're going to give somebody a fecal transplant, then they should be trying to replicate the lifestyle of the person that they got the donation from. Because otherwise, they're probably not doing the things that are going to encourage those microbes to stay around. Um and and that's why often when you look at these fmt studies you might get an initial improvement and then it sort of tails off um by three months down the line you know there's there's then no discerning effects left um which you know until we address the sort of lifestyle side i'm not sure you're going to see such long-term success with with fmt and you know jack thinks it's impossible to change everybody's lifestyle. I disagree. As a lifestyle medic, I've seen people change their lifestyles pretty dramatically. And I think if people are motivated, if they have the motivation of potentially getting rid of a chronic disease, that might really drive them towards some really positive changes. What do you think?

Guest:

John and I talked about this a lot because we would kind of see the 80-20 rule in people with Parkinson's, and there was about 70% to 80% of people we would meet kind of accept the diagnosis, sit down in the chair, and just wait for the progression. And that other 20% to 30% are actively working on changing their lifestyle, their exercise, educating themselves on diet, and, really trying to change the lifestyle to have a better outcome. And, you know, if I look at the probiotic I made for John, I mean, its original goal was targeting mannitol. Well, mannitol is an osmoregulator, so it helps with constipation. So that was one of the first feedbacks we got. But it actually, the process of it making the mannitol, it's converting glucose and fructose into the mannitol. So it's removing those sugars that are causing other problems and feeding some of those pathogens. And what I had also seen in people with Parkinson's was many of them had a very severe sweet tooth and craved sugars. I think some of that may be the insulin resistance in the brain that there's some research showing that. There's definitely glucose dysregulation in the system and how that is making its way to the brain. But I've also talked to a couple of people with Parkinson's who didn't have a sweet tooth before they got Parkinson's, but after they started taking the levodopa carbidopa, developed a sweet tooth. So I think there's some things to look at there in terms of how does that impact the microbiome and those microbes that may be giving you those cravings. But the probiotic that we made, we went on to actually bring it to market. It's called Sugar Shift. And we studied it. We did a clinical trial in diabetes and. One of the metrics that I wanted to look at, because it also translates to Parkinson's and other things, is serum endotoxin or serum LPS, which is the cell wall components of those gram-negative bacteria that are inflammatory. And in our trial, 100% of the participants who took the probiotic had a significant reduction in endotoxin. And there's an endotoxin model, animal model, of Parkinson's. So, I think, and one of the things that people tell us is it does help them eat less sugar. So, I think, you know, having a coach or a doctor who really talks to them about how lifestyle changes can have an impact. And at least here in the States, we don't get that kind of education. One, the doctors aren't educated on the lifestyle medicine. And two, our system of reimbursement is not designed to allow a reimbursement for a doctor to spend time educating a person. So that's actually a lot of what I do is, you know, I talk to Parkinson's groups about diet and exercise. And my husband was very involved with Jay Alberts of the Cleveland Clinic, who was one of the early pioneers in showing the impact of exercise on Parkinson's and the biking programs that you could reduce your Parkinson's symptoms by about 35 percent by doing this stationary biking program three to four times a week for an hour. And so John was very involved in getting those programs set up in the United States, in YMCAs and different places where people with Parkinson's could access the exercise.

Sheena:

And it's not just, you know, cycling. I mean, all sorts of exercise can be really beneficial. And Parkinson's patients have this interesting phenomena that when they exercise, a lot of their Parkinson's symptoms switch off, don't they? Because there's actually a Parkinson's exercise class down the road from my surgery. It's a ballet. It's in the sort of Glasgow Ballet Center. And one of my patients actually goes there. And he says that he feels amazing when he's there because all of his Parkinson's symptoms go away. And he can dance really, really well. And I think that's amazing. So that can be very freeing for patients with Parkinson's. To be able to take part in these kind of things and feel a bit more normal again. That's great. You mentioned some probiotics when you were talking there that you had John on. And often we talk about fermented foods in the podcast. And what would you say is more beneficial? Would you say it's more beneficial to go down the fermented foods line or the probiotics for patients with Parkinson's?

Guest:

I typically recommend that people do both. Fermented foods are, the nice thing about fermented foods is they are this ecosystem community of microbes that are working together. And that's actually how we designed our probiotics. But one of the strains that's in all of our formulas, so I had a big focus also on the food and what was in the food. And glyphosate was a big focus of mine. And so I wanted most of the lactobacillus and bifidobacteria are killed by glyphosate. And those are really important in our gut. And we actually found a strain of Lactobacillus plantarum that we fermented from elderberries, wild elderberries. And it was resistant to glyphosate and could actually break it down by a pathway that basically turned it into phosphate, hydrogen, and water. So all the way back to the elements and harmless. And a lot of microbes can partially break it down, but will produce something that's more toxic. So I think that's actually, you may or may not get that in a fermented food. You may get a microbe in there that can do that. And apple cider vinegar with the mother in the vinegar will often have an acetobacter that can break down glyphosate. So I like to give people different tools, but I do think that a good quality probiotic can be beneficial. There's also another company called Neurly. I don't know if they're in the UK, but they're here in the States. I think it's a Korean company. And they have a strain of lactobacillus plantarum that they've done quite a few studies in Parkinson's. But we sequenced it. It doesn't have the glyphosate remediation, but it has some other mechanisms that are helping. And there's a strain of bacillus subtilis that's being studied at... I think um that uh they've shown can reduce tremor in animal models um and we have uh we use a strain of bacillus subtilis in all of our formulas but that there are often you'll often find a bacillus subtilis or those bacillus soil microbes in a fermented food so i like to encourage people to you could just even if you don't love fermented foods you can have a little you know a teaspoon a tablespoon of, you know, sauerkraut or kimchi with your meal. And that's going to help you with the enzymes to break down the food and access the nutrition. And I think that's actually maybe one of the reasons why we see, you know, healthier data from Asian cultures, because they do eat a lot of fermented foods with each of their meals.

Sheena:

Interesting um and you know we sometimes forget that these individual microbes have such interesting um properties to them and can make such impact and why do you think it's so important for us to break down that glyphosate or get rid of the glyphosate because you mentioned the importance of going organic earlier um and obviously so much of our food is sprayed you You know, so much of our fruits and vegetables now are sprayed with pesticide, and glyphosate's the most commonly used one, and sprayed quite heavily. So why do you think in Parkinson's patients it's important to remove the glyphosate?

Guest:

Well, so there's something called the shikimate pathway, which is the target of glyphosate. And humans don't have that pathway, but microbes do and plants do. And so when we're overusing that chemical, we are breaking that pathway in all of those systems. And there are three aromatic amino acids, tryptophan, phenylalanine, and tyrosine. And that pathway is also the pathway where dopamine is produced, melanin is produced. And it's produced by either microbes or plants. So if we're breaking that pathway over and over again, we are disrupting those key amino acids that we only get from food or our microbes, and they are involved in the production of dopamine. And many, many—so that pathway, when you start to look into microbial production in the shikimate pathway and in plants, there are about 8,900 secondary metabolites that come from that pathway. So, you know, obviously they're there because we need them. Yeah. That constant hit to the food supply and to our microbes is just going to be a chronic problem if we don't deal with it.

Sheena:

Yeah, and there's not actually very much research on glyphosate and the microbiome, sadly. I have looked for it. I've done some of my own research there, and there's very little. I do the the small number of papers I did manage to read on this did show quite a destruction in the the diversity of species in the gut so is they are damaging to the gut microbiome but we definitely need more research in this area because I think it's a really important area we are putting this on our food supply and and actually if you go to a a whole food plant-based diet, which would obviously be a healthy diet to move to, but you don't go organic. I have read that you increase your pesticide exposure by seven times.

Guest:

Yes, it's really, really significant when you, you know, for a vegan diet would have a very, very heavy load of glyphosate.

Sheena:

Yeah, so it could be potentially a big health issue for a lot of people. So, yeah, we need more research into glyphosates and into pesticides. So let's go back because you also mentioned dopamine there. And I think, you know, just to really inform our listeners on Parkinson's. So dopamine is really one of the main neurochemicals, neurotransmitters that is involved in the pathogenesis of Parkinson's disease. And a lot of these neurochemicals are produced in the gut by gut microorganisms and we have the ability to manufacture them in the gut. Can you tell us a little bit more about dopamine and the relationship between dopamine and the gut microbiome?

Guest:

All of these neurochemicals that are produced in the gut, you kind of have this loop between the gut and the brain. And a lot of this communication is through the vagus nerve. Actually, one of the researchers who's done the most work on the connection to the microbiome in the brain and these neurochemicals is John Cryan and Ted Dinan from the University College Cork. And I don't know if you've had them on, but.

Sheena:

Yeah, not yet. If they're listening, come on my podcast.

Guest:

Yeah, well, Ted, actually, Ted Dinan is one of the very first people I met at a microbiome conference before I started the company. So, you know, dopamine is what, I'm not going to do a very good justice to this, but in Parkinson's, I'll say what the dogma says is that by the time you're diagnosed with Parkinson's, the dopamine-producing neurons in the brain are about 70% gone. I'm not sure we can know that with certainty because neurons have some flexibility and ability to regenerate. And the only way we really know what's going on there is through an autopsy when you're already dead. And you're putting more dopamine into the brain with medication. So I think there are pieces of that puzzle that are missing. But we are producing dopamine and serotonin and, you know, all of the amino acids also in our gut with these bacteria. And so you can get into these stress loops. Stress is a big factor. In Parkinson's, there's a kind of a perpetual state of fight or flight, which is also using up dopamine and a number of these neurotransmitters. And that is, I think sometimes, you know, if you think about, I'm going to move from dopamine to opioids, but in somebody who has an opioid addiction, the body starts to turn off the brain's ability to get the stimulation from the opioid in an attempt to protect you from yourself because you don't get the enjoyment. But what happens is people take more and more opioids to get to what they are. And in some ways, if you look at the course of dopamine treatment. The body is also getting accustomed to the dopamine drug and starting to turn off that mechanism so that over time you have to take more and more of the medication. So, I think there's a lot still to be unraveled in that gut-brain connection with those neurotransmitters and what's going on.

Sheena:

That was really interesting. your answer but it's a it's a really complex area um i mean 50 of our dopamine is produced in the gut and the rest is produced in the brain um there is in between that there's a blood brain barrier um which will only allow certain things in so actually dopamine that's produced in the gut um i don't think it can cross that blood brain barrier but we have the pieces that we need to create it in the brain and the bacteria metabolites that can help with that production can cross into the brain so so there are still although it's being created in the brain some of the most important dopamine that we use is being created in the brain we still can influence that with our microbes indirectly through the metabolites and through the crosstalk through the the nervous system and through the hormonal crosstalk as well in the brain is it's such a complex area and i definitely need to get um get the guys from dublin in onto my podcast to talk in more depth on this because it is really really interesting um but but it's interesting that you know this is this is a part of uh the parkinson's is actually key and as you say the the parkinson's treatment sort of focuses on giving the body back that dopamine which is what the medications are doing. Interestingly there's a big connection between the vagus nerve and Parkinson's and my understanding is that if you have a vagotomy so if your vagus nerve is severed now vagus nerve is a really important structure, which is essentially the neuronal crosstalk between the brain and the gut and all of the viscera. So all of the internal organs talk to the brain through the vagus nerve. And the vagus nerve is responsible for our parasympathetic nervous system, which is the bit that's sort of more relaxing. And it helps to drive our heart rate and our respiratory rate. It helps to drive the motility of our gut, which is obviously key in Parkinson's. And interestingly, they have noted that in days gone by, in the 1970s, they actually used to sever people's vagus nerve connection to the stomach to treat ulcers in the stomach. And there were a number of side effects to doing this, gut symptoms and changes in motility. But one of the things they noted is that people that had had this procedure didn't develop Parkinson's disease, which I thought was a really interesting phenomena. You know, you have to have that connection intact for you to develop Parkinson's disease. So there's something about that nervous system connection between the gut and the brain that seems to be really important. What have you discovered on that?

Guest:

Well, there's actually been some interesting research here. I can't remember the guy's name, but he's at Johns Hopkins. So alpha-synuclein is the protein that aggregates. It's also interesting that alpha-synuclein is actually what's called an antimicrobial peptide, and it's nonspecific. So it's trapping microbes that are a problem. But this research actually showed in an animal model that they could transport that alpha-synuclein up the vagus nerve in the animal model by seeding the gut with alpha-synuclein. So, you know, I think it's a superhighway for a lot of things. I also think, you know, the gut is called the second brain, but I think we're still in an early research paradigm. I mean, what if the gut's our first brain?

Sheena:

Yeah.

Guest:

You know? And so it's making dopamine if, you know, if it's able to make the dopamine with the right kind of microbes and—, I mean, we know we get a gut feeling. So I don't know. I think there's a lot left to learn there and that, you know, what's going on with that communication. And I'm also interested in the work of, so sleep. So, you know, if that alpha-synuclein is moving up into the brain, when we sleep at night, if we get good quality deep sleep, which people with Parkinson's often don't get, that is when the brain clears out the trash into the cerebrospinal fluid and we're flushing the system. And if you're not getting good quality sleep, then you're not able to take that trash out. And it's kind of like a freeway where people are getting backed up in the off ramp of unable to clear out their trash. So that's another area that I often talk to people with Parkinson's about really making sure they focus on their quality sleep. And again, that goes back to the gut again because that serotonin and tryptophan are made in the gut by bacteria. Absolutely.

Sheena:

So that's the glymphatic nervous system, isn't it? Which only sort of starts off when you get to that really sort of level four non-REM sleep, when you get to that really deep level of sleep and that kicks in and it's a long, slow pulsation of lymphatic fluids through the brain, which clears amyloid and toxins and all these incredible sort of metabolic byproducts that we don't really want in there. It clears them away to allow you to sort of start refresh the next day. And actually that bit of our sleep dwindles as we age anyway. So we start off in life with quite a reasonable amount, an hour and a half or two hours of that sleep. And then that gets less and less and less as we get older. So it's harder to get that anyway. But if you have a chronic disease, you're much less likely to. And like you say, that really connects to the gut again, because how do we get a good night's sleep? Well, you need a high fiber diet and you need the right nutrients to get a good night's sleep, as well as being stress-free and getting some exercise and all of these things really improve your sleep. So yeah, I mean, that holistic approach, I think, must be really, really key again for our patients with Parkinson's. So it's really interesting. Where are you at now with your research and Where are you going? What are you doing right at this moment?

Guest:

So I'm actually working on the paper with Dr. Nenum in Australia about this colloidal, just kind of an overarching rethinking of Parkinson's and what's going on with this key piece of the microbiome as part of that puzzle. But really trying to, he's a physical chemist, to understand better and explain better all of the different pieces and how they fit together. So I'm excited about that. And then I'm actually working with a new Parkinson's foundation called Resolve Parkinson's to put on a meeting next May where it'd be like a three-day brainstorming with a premise kind of like, what if everything we think we know is actually wrong? And looking at taking a completely different perspective—. Parkinson's, you know, going to the other side of the room and looking back. And as a part of that, we're also making a documentary of people with Parkinson's telling their stories, because I think this is also another piece of the puzzle that is often missed because of the short doctor's appointment, the fact that doctors don't know us like they used to 100 years ago. Where when you start to listen to people's stories, you pick up these patterns that are being missed. I mean, I'll give you an example. I talked to wives of men with Parkinson's support group a few weeks ago. And one of them was talking, we were talking about vision and how, like, I always felt like John was not seeing exactly as I was seeing. And, you know, we had this discussion about it because it felt like the earth was falling away from him, and that's why he was tipping forward. And in talking to this group, you know, there were only 10 women, but out of that 10 women, I think three or four of them, husbands, had to have prism glasses. They were seeing double, and many of them had the vision problems before they were diagnosed with Parkinson's. And so that actually ties to the research or the colloidal chemist research of what's going on in the eye, too, in that vitreous humor. So anyway, so we're going to kind of piece together this set of interviews and really try to paint a picture of the pieces that a doctor may not be seeing or understanding. And many people with Parkinson's have triggers or things that they've observed that may have either contributed to their Parkinson's or make it worse that kind of get ignored at the appointment. So I think that's going to be an important part of it. So if anybody's interested in doing a Zoom interview for that, they can contact me through my Martha's Quest blog.

Sheena:

Fantastic. So I'll get you to give me the details. We can put it on our podcast script. So, yeah, I mean, I think it's a real shame. This is the trouble with modern medicine. We don't have the time anymore to be really spending with patients, to really pick up on these kind of patterns and interesting things that you might notice about certain cohorts of patients. And I think, you know, we're losing a lot of the skills in medicine around, you know, just observation of patients. Yeah. So I agree with you. I think it's a real shame. And I would really love to see medicine getting some of that back instead of a sort of over-reliance on radiology and blood testing as a way of diagnosing. I think, you know, it's really important that we pick up on these observations and we're able to act on them and be scientists. And I think, you know, that's why people like you, Martha, are so impressive because you've come to this from a position of being an accountant and you've trained yourself to be a microbiome scientist, but not just that, you've also trained yourself to really be a researcher and somebody who really takes note of people and is incredibly holistic. And, you know, I think that's really, really impressive. And I think it's only with that open-mindedness that we can really progress science, which I think is amazing. Martha, I know you wanted to talk about John a little bit. And, you know, I was really, really saddened to hear that John passed away a few months ago. So I really want to say I'm very sorry about that. Tell us about John and tell us his story and how you think your research has impacted him.

Guest:

You know, John was just this amazing person with such a tremendous sense of humor and vitality. And he contributed so much to the Parkinson's community of giving people hope because he tried things with enthusiasm and when it worked he shared it with um others in the community um, But he actually, he had a pulmonary embolism in September, and typically people would think that maybe that's not connected to Parkinson's. But I actually have a presentation on our Biotiquest YouTube channel on Parkinson's and molecular mimicry, and another one that I've done for the Parkinson's Association of the Rockies, where I have this diagram of kind of the cascade over time of what's happening, of inflammation, neuroinflammation, vascular inflammation. And you're getting aggregation of the proteins, but you're also getting some coagulation of the blood. And, you know, ultimately over time, that's sort of building up. And part of my hypothesis is that there is a chronic low-grade polymicrobial infection in the microbiome that is systemically affecting the body. And while, you know, we did a lot of things to improve that, and John had a tremendous quality of life until he had COVID, COVID accelerated that inflammation and that coagulopathy, and that is what, you know, potentially led to that blood clot. But, you know, what I would really say is, you know, a lot of times John and I talked about, like, did we come here to this earth to do this together to help people? We actually met in college and then didn't see each other again and ran into each other 13 years later in a bar in a totally different state. And I always say it was meant to be.

Sheena:

Yeah. Yeah. It sounds like it was. And he's been your motivator and your driver. And, you know, it's impressive what you guys have achieved together with all of this. And you're continuing to take this forward. You know, despite him not being at your side anymore, you're still there and you're still desperate to find answers for the other people in the world that are suffering from Parkinson's. And I think, you know, congratulations for all of that, because I think that's that's an incredible bit of work that you're you're doing there. And it has the potential to help so many people. So I'm really thrilled that you're you're doing the work that you're doing, but obviously sad that John's not still there. Um, so, and interestingly, what you said about COVID there, um, because a lot of people might not realize that COVID itself can be quite disruptive to the gut microbiome. Um, and, and it's interesting that a lot of people, uh, have noticed worsening, um, symptoms of chronic diseases after COVID and it depletes your bifidobacteria in your gut, doesn't it, COVID? Yes it does yeah.

Guest:

That um and um sabine has on in california has done a number of research projects on that and um is actually looking at how to address that.

Sheena:

Yeah i think i've heard a podcast with sabine she's very impressive she's she's really interesting on all of this um fantastic well i just want to thank you again for coming on today i think this has been a really important podcast is something that can give people a lot of information on the gut brain and the importance of microbiome research in trying to determine triggers, causes, you know, and to find answers for chronic diseases like Parkinson's disease. And the research you're doing is really going to help drive all of this forward. So I'll put the information about your quest and the work that you're doing onto the podcast notes. Was there anything else, Martha, you wanted to mention in this podcast? Anything that you feel we haven't covered up until now?

Guest:

No, I would just say, love your microbes. You are more microbial than you are human. The range is maybe 100 to 300 times more genes in your gut than your human genome. And so really think about this part of yourself. We don't want to kill this part of ourselves we want to nurture it we want to provide it what it needs to flourish so that that part of us can really make us whole.

Sheena:

Amazing yes that is definitely the message we want to get across to people and any clinicians listening you got to keep thinking about microbes and and what they have to do with everybody's ill health everybody's disease because this is really important going forward and we need more and more clinicians to be aware and more and more clinicians to be using this information and helping their patients going forward. So thank you so much, Martha. It's been an absolute delight chatting to you today. I've learned a lot and I'm really fascinated with your work and I'm going to keep in touch and keep finding out what you're doing next because I think you have the power to really find more answers than a lot of people are at the moment. So well done. So thank you, everybody. I hope you've enjoyed today's podcast and I'll speak to you next time. Take care.

Intro and Outro:

Thank you so much for listening to this episode of Microbiomedics Podcast. We really hope you enjoy the content and we welcome your feedback. We'd love to hear any suggestions you might have for microbiome topics that you'd like us to cover and we also appreciate listeners' questions and we'll endeavour to answer them in the next podcast.