103 Inflammatory Mechanisms And Biomarkers In The Chronic Manifestations of Lyme Disease-Alaedini, Armin

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Welcome, welcome to this episode of Lyme Voice, and I am here today with Dr. Armen Aladini. Hu is a professor at Columbia University where he leads a research laboratory focused on studying the role of immune system-host-microbe interaction and diet in complex disorders. He received his undergraduate degree in chemistry from The Ohio State University and completed his doctoral research in protein chemistry and bacteriology from University of Cincinnati. His team's research on Lyme disease in the last 15 years, plus 15 years, has focused on the chronic and post-treatment manifestations of the infection, leading to seminal findings that provide molecular evidence of a biological basis for patient symptoms. Thank you so much for being here with us.

Thank you. It's a pleasure to be with you.

Yeah. So we got to meet Dr. Armin at the Live Lyme Summit, and one of the highlights of that conference for both Aaron and I was sitting with you and Dr. Tom after the Saturday sessions and just getting to pick your brains.

It was, it was a pleasure and fun for, for us as well.

Yeah, we sat there for almost a couple hours, had a couple rounds of drinks and tried to solve the world's problems.

That was fun. And that was sort of one of the— I go to a lot of meetings, but that was certainly a memorable meeting, especially because of that interaction with you guys, with you and Aaron.

Yeah, that was definitely the highlight for us. So tell us what you are doing over at Columbia University, because, um, you talked at the conference about inflammatory mechanisms and biomarkers in the chronic manifestation of Lyme disease. And when I looked you up, it says Aladini Lab at Columbia University. So this is your lab.

Right.

Your project.

Well, yeah. So I am a faculty member at Columbia University. So I have a lab, I've had a lab there for the last, since 2011. And the focus of my research and my team's research has been on how dietary and infectious agents or antigens or molecules can lead to chronic inflammation, what are the mechanisms for that? So, um, certainly Lyme disease is, is one of the major focuses of, of the lab, but we also focus on how foods can, can lead to chronic inflammation, uh, through, uh, changes in the gut ecosystem, what's going on in the, uh, gut, uh, ecosystem, including the microbiome and the immune system there. And it's not entirely unrelated to the case of Lyme disease, and I can get into that later. But in the case of Lyme disease, you have an infection that causes inflammation, and we're interested in how that inflammation goes on to become chronic. So there are different hypotheses as to what is causing the chronic symptoms in patients who have had Lyme disease. And independent of what the actual causative original agent is, we believe that there is a persistence of inflammation, and that we think is responsible for the patient's symptoms. And we're trying to understand how that is happening. And, you know, when I started in this field, really, there was very little or no research in this area, and there was people basically saying that this may be in patients' heads, that it doesn't even exist, that there isn't a biological basis for the patient's symptoms. And what we've done in the past, I would say, 10 years is publish papers to show that patients with these chronic or persistent symptoms after treatment of Lyme disease do have persistent inflammation that is associated with the symptoms that they're experiencing. So now we know that there is, I think there is now a consensus that these patients really do have abnormalities in the immune response. Now whether how directly that is related to the original infection and what are the mechanisms for that, that is still under study. But we do know that these patients have this persistent inflammation, that there is likely to be a very real biological basis to what patients are experiencing, which was not, which is not trivial. I have to tell you, this is not trivial. You know, people may think, well, that's obvious. Well, scientifically, that's not obvious. It took a lot of research to actually demonstrate that.

That was my exact thought when I had read that statement at the conference. I was like, of course there's gonna be something biological. Like, we're all suffering, we're all saying the same thing in different ways, and there's there's so many of us all over the country and the world who are dealing with that. And it just seems to take a lot of time to get down to the specifics of why.

Yeah. I mean, to patients, it's obvious that there is something going on, but this, but scientifically there is this, you know, a way to prove something. There is a sort of a path towards scientifically proving something. And it's not trivial to say that, you know, that there is a biological basis. You got to start somewhere, you got to have controls, you got to do a very methodical research to actually demonstrate that what people who have had Lyme disease and go on to have chronic symptoms, what they have is different from people who have had Lyme disease and go on to have no symptoms. And you have to do careful studies comparing these exact two groups. You can't compare people who have had chronic Lyme symptoms to people who are completely healthy and never had Lyme disease. So you got to, you know, recruit the right patients, you got to do these studies well controlled to be able to prove this. So it takes a lot of research and with that, of course, funding to actually be able to, to prove that exact point and to understand the mechanism by which that is actually occurring, which we are, which we're doing.

So when you say mechanism, do you mean like the mechanism that originally causes the infection or the the body's response to the infection.

The body's response, exactly, the body's response. Well, we know that the infection is caused by Borrelia burgdorferi. There is no doubt about that. But why do some patients, why do some people recover fully and others don't? That is the question. And that is dependent, we believe, on the patient's immune response. You can think of it, like putting out a fire, you know. So you have a fire, so an infection causes something that's like a fire, and inflammation is like a fire. Any infection causes inflammation, and that is required for taking care of that infection. So you need to basically have an inflammation to respond properly to an infection. But after the infection is over, the body has a regulatory system. The body's immune system comes in and actually puts out the fire as well. So you, now that the infection is gone, you got to actually get rid of that inflammation as well. And that is what we think is disrupted here, that is defective, that the patient's inflammation is not being properly addressed by the body. And that could have different reasons, but, you know, it could be genetic, it could be because of the Borrelia themselves, it may be because of Borreliose components that are remaining happening in the body of patients. There are different hypotheses and there are different pieces of evidence for some of this. And I'd be happy to go through some of that as well, as I did, you know, during the meeting.

Okay, yeah, go ahead and do that. And then I've got a couple questions for you.

Well, you know, as I explained, so there is, as I said, the data that we have so far really does indicate that patients have a persistence of inflammation. Now, what is causing that? We don't exactly know. And one of the, hypotheses that has been out there, and there is some evidence for, is that there is spirochetal debris, that is a persistence of Borrelia components in the body. And that— the evidence for that comes entirely from animal experiments which show that even with antibiotic treatment, you can have persisting Borrelia in the body of the animals. Now, these Borrelia that are persisting are not cannot be cultured. People have found spirochetal components, that is molecules, proteins, or non-protein components that are persisting in the body of the animal. Now, whether— what exactly the nature of these components is and what they're exactly doing is not clear, but we know that those components can be inflammatory. That is, these you have something that is remaining in the body of these animals and maybe triggering the additional immune responses and inflammation. Now, this data all comes from animals. We don't have human data on this. I have to— we don't have reliable human data on this showing that this is happening in humans. The other thing is that all of this data indicates that these things exist in the, the body of the animals. But what is the relevance of that to patients' symptoms. That is, nobody's actually looked to see if these animals are experiencing the symptoms that the patients are experiencing. And that is a really important missing link because it relates to relevance of the animal model to what humans are experiencing. And so in, in research, especially preclinical research, which is what we're talking about here, you have to— you want to build a model that closely reproduces or replicates what patients are experiencing, right? And these models don't. So what we need, and I mentioned this if you recall during the conference or during my talk, that we need a better model to replicate what patients are experiencing. And currently we don't have any. And one of the things that I and my team have been really wanting to do is to build a proper model that actually reproduces patients' symptoms. So nobody's, for example, looked properly to see what happens to these animals, what are they experiencing, do they have fatigue, do they have cognitive dysfunction? These we can now do. We have the techniques, we have the technology to do it. So we actually, I really believe that the next step for us is to do that. But what we do know through the research that we've done in my lab is that patients, all of my work in the past has been on actual patients with the chronic symptoms, that patients have a persistence of inflammation that is different from the inflammation that patients with early infection have. It's a different kind of inflammation. But we've shown that these patients have elevated levels of antibodies to autoantigens. Almost similar to what we see in patients with certain autoimmune diseases. That doesn't mean that the condition is autoimmune. I'm not implying that because we don't have all the evidence to say that there is an autoimmune response going on here. But we do have evidence to show that there is inflammation that is resulting in the production of autoantibodies that is not unlike what we see in certain systemic autoimmune diseases. We also see what we call acute phase inflammatory response markers such as C-reactive protein being elevated in these patients. We also see that in very early infection, but it's different from— it's slightly different, the nature of this inflammatory response. But we do see this inflammatory response that we don't see in people who recover fully. So we have actual biological markers to demonstrate that patients with these symptoms have chronic persistence of inflammation. And that's really important. Again, I don't— I want to really stress that fact that this is really important because it gives us a handle to study patients, that we can even use this to recruit patients to be able to study them better. It's in research. It is really important to have a homogeneous group, because when we have patients that have ideologically different conditions, it's hard to study them because you won't be able to get results that are statistically significant. But if you can recruit patients that, that are more homogeneous ideologically, then you can actually get significant responses. And if you come up with a treatment strategies, it's also important to have biomarkers to recruit patients who are more homogeneous because again, you will be able to demonstrate efficacy of your treatment strategy because again, you recruited them based on a biomarker.

So why has— or how— it feels like it's taken us a really long time to arrive at this place where we do have biomarkers considering Lyme has been unfolding for decades? Like, when are we— are we just barely tapping into what it's going to take to get people like the AIDS epidemic in the '80s? Like, how, how far away do you think we are from still offering viable treatment solutions for people with chronic Lyme?

I think the main problem has been the lack of funding. For this research. If you compare— you brought up HIV, so, you know, compare the funding to that, we're talking about a tiny, tiny, tiny fraction of that. There is basically no federal funding for Lyme disease. I mean, if you look at the funding that is given out by NIH for Lyme disease, it's very, very small. It's minuscule. So, The lack of funding, I think, is a major reason why we haven't made significant strides in addressing this. We know that, you know, we know a lot about Borrelia, we know a lot about the infection itself, but the chronic symptoms that patients, that a significant proportion of patients experience after having Lyme disease, that's not, that hasn't been properly studied. And that, I think, is the major problem. Part of it, of course, has been a period when this was dismissed altogether. As I mentioned earlier, that there really isn't any biological relevance to your— or connection to symptoms. But now we know that there is, and I think the research is increasing. If you just look at, for example, the number of publications by major or from major universities, you'll see that the number of publications where they've studied these chronic manifestations of Lyme disease is increasing. It's still slow. It's still not adequate, but it points to greater attention given by serious scientists to the problem. Nevertheless, we really, really need more support by NIH and other federal agencies federal agencies to this problem.

So how does— how do you actually get funding? Because we have interviewed so many physicians, a lot of who have operated in the cancer realm beforehand. And so whether it comes to grant writing or research funding, over and over again, we keep hearing this, that there's just very little, little money within the Lyme community compared to AIDS or cancer. So where, how do we as the public change that tide or can we?

Yeah, I think we can. And I think there has been a movement in the past, I would say decade or a little more by the formation of patient advocacy groups that have spoken to their representatives in the government, in Congress to increase funding. There has been some movement, but I can tell you a little bit a little bit about my experience, for example, with chronic fatigue syndrome. I also do chronic fatigue syndrome research, and recently I was on a working group of an advisory council to the NIH on how to basically help increase research in chronic fatigue syndrome in that area. Again, chronic fatigue syndrome is also, there is of course a huge overlap between chronic fatigue syndrome chronic manifestations of Lyme disease. And I really think that actually a proportion of chronic fatigue syndrome patients may be former Lyme patients. So if you go back to that, to chronic fatigue syndrome, where there again has been very little funding, now slowly NIH is starting to be, I would say, more supportive of research in chronic fatigue syndrome and thinking about strategies to, to better support it. And one of the problems, for example, is that there aren't that many serious researchers with the expertise to study chronic fatigue syndrome. Chronic fatigue syndrome is again a heterogeneous condition. It's a spectrum disorder. It's very difficult to study. Funding has been little. Patients have been— people have been dismissive of the symptoms that the patients have been experiencing. So it really parallels what's been going on in Lyme disease. But as I said, NIH is now starting to pay attention to it. And one of the ways to do this is to actually support or increase funding and to actually have a dedicated group at NIH that reviews grants in chronic fatigue syndrome. That is a huge, huge step. And I should, you know, congratulate NIH for actually doing this. It's a huge step because grants that are sent in by people who are requesting funding such as myself, let's say Lyme disease, they go to a what's called a study section. And I've actually served on these study sections. The job of these study sections is to review grants that are coming by experts expert scientists. So the people who are sitting on these panels are considered the best in their fields to review these grants. Now, the problem with Lyme disease is that there isn't a single study section that actually reviews Lyme disease grants. There is a study section that reviews Lyme grants, too, but the people on that study section— there is more than one. There's 2 or 3 that grants may go to, but most of these study sections have either just one or no person who has ever done Lyme disease, you know, research. So that shows to you that people who are reviewing these grants may not have all the experience or expertise to be reviewing Lyme disease-related grants. And when people who don't know a lot about Lyme disease review grants about Lyme disease, you can see that, you know, some problems can arise from that. They may not recognize the importance of research on the persistent symptoms of Lyme disease. The same thing is happening with chronic fatigue syndrome, but now there is actually a study section where people who are doing chronic fatigue syndrome research can actually send their grant applications specifically to that study section. And so everybody who— every expert who's sitting on that study section knows about chronic fatigue syndrome has some expertise. And so there is no case where a grant goes to reviewer and the reviewer says, I just don't think this problem even exists, which can happen. Yeah. And has happened, for example, to myself when I have sent grant applications on post-treatment Lyme disease syndrome or chronic manifestations of Lyme disease. I have actually, you know, there are cases, and I'm not the only one, there are other investigators who have sent in grants And they have received the response basically that we don't even think this problem exists. This is not a real condition. Or they may not recognize, they may not understand the extent to which this has an impact on public health and the patient community. So that is a problem. And as I mentioned, in the context of chronic fatigue syndrome, that's being addressed. The other thing is that You know, in academia, we have— we train new scientists, right? We train graduate students, we train postdoctoral fellows, and they have to go on to continue the research that we are doing. And problem is that when we don't have much funding in this, they look at this and say, like, I don't want to go into chronic fatigue syndrome research, I don't want to go into Lyme disease research because there isn't any funding in this. I'll go into HIV, research, I'll go into, you know, cancer or diabetes research because there is more funding in that, or I'll go into Wall Street where there's a lot more money. And to be honest with you, I have had students and research fellows who have gone to Wall Street because they just noticed how difficult it is to get funding in the area of research that we're working on. So it is also important to support to support young investigators by providing funding for them, by having conferences that focus on these areas of research that are generally— you don't have a lot of conferences for. You know, one of the things is that we struggle with, I struggle with, you know, students ask me or fellows ask me, well, where should I, you know, present my research? I want to go to a conference. And I said, well, let's go to a neuroscience conference or let's go to— but when we go there, you know, the level of interest in these areas is not a lot, is not great. So we need conferences, we need support from, you know, advocacy groups and the government to, to have meetings, to have conferences that directly relate to these conditions that for which there isn't a lot of funding. It's a vicious circle. But for example, in chronic fatigue syndrome, the NIH just had a conference earlier in the spring. I go back to— I keep going back to chronic fatigue syndrome because I think that's an area where we can look at, we can look to as an example of how we can basically push the Lyme disease research forward. We can look at it as a model.

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Um, basically push the Lyme disease research forward. We can look at it as a model. Hmm.

Well, so you were saying if, if we're struggling to find biological markers, if you guys are struggling to find that, then that impacts like, what's your perception on the level of testing that's available to the public at this point? Because if you guys are struggling to find those biological markers, the tests are years behind that. So how does that play into things?

I think, I think we're making strides. So I have to sort of step back and tell you a little bit about the testing for Lyme disease. So most of the tests, or all of the tests that are accepted and considered mainstream for Lyme disease, rely on the immune response to the infection itself. Right. And as you probably know, when we get an infection, it takes a little while for the immune system to realize that. We have two different types of immune responses. There is one that is rather nonspecific, and it's called the innate immune response. Now, that kicks in very quickly because it doesn't care what kind of infection you have. It kicks in very quickly. It's not specific to Lyme disease, though. So if you have another infection, it'll looks similar to that. And so you have inflammatory molecules in the body that can start being secreted within hours even of an infectious disease. However, there is another immune response that kicks in slowly, much more slowly, that is called the adaptive immune response. As the name implies, that's much more specific, and that is what's used to determine with certainty that a patient has Lyme disease. Now, independent of how reliable that test is, I should, I should mention that when the patient gets Lyme disease, in the first few days there is no adaptive immune response. So if you test the patient, it will come out negative. So the testing that we currently have for Lyme disease is not effective in the first 1, 2, even 3 weeks sometimes of the infection, and that's a problem. Yeah, there are other immune responses, as I mentioned. For example, the innate immune response, and which I think personally, and we've published on this, can be utilized to determine with some certainty that patient might be having an infectious disease, including Lyme disease. It won't tell you that the patient definitely has Lyme disease, but you can sort of, you know, combine the clinical assessment, you know, with that biomarker to say, well, this patient probably has Lyme disease, most likely have it, has an infectious disease, and Maybe I can come in with an antibiotic treatment. Now, of course, the bullseye rash, that's something that can be seen, but as you know, not all patients get the bullseye rash. So that's also another problem. So we need a test in that very early stage of Lyme disease to be able to confirm with more certainty that the patient has Lyme disease. Now, that's the very early time. The problem is that if the patient is treated later on, the chance of the patient, that the patient will develop persistent symptoms increases. So it is important to treat the patient as quickly as possible. Now, if the patient has had Lyme disease for a while and it's still an active infection, that is, the organism is still in the body, it's still replicating, it's still very active, most patients do have a very robust immune response from the research that we've done and others have done. So if the infectious disease is the stereotypical active infection and had a patient has had it for more than a month, you will see a pretty robust immune response. Now, if you treat the patient, some patients get better, most patients do get better, but there is a significant proportion that don't get better. And that is the proportion that I have been doing research, and I think that's the patient, the proportion of patients that you're talking about and that, you know, we have a problem with addressing their symptoms and what they're experiencing. And those patients may have an immune response, they test positive, but there is no way to differentiate them from people who get better because they also have that adaptive immune response to Lyme disease. Or maybe their, their immune response has disappeared now because after a while the immune response goes down. But they do have the symptoms. And what we've tried to do is find biomarkers for that group of patients as well. So I don't know if you recall, but I showed a plot and where the unmet needs in the case of Lyme disease are. We have an unmet need to identify and diagnose patients in the early, earliest stage of Lyme disease and in this later post-antibiotic treatment manifestations or persistent symptoms of Lyme disease. These are the two areas that we really need to address. And, you know, for a long time, all the studies on Lyme disease were focused on the middle part where there is an immune response and you can diagnose this— diagnose it fairly well. But what we need is in that early stage and in this very late stage related to Lyme disease where we need to find biomarkers, where we need to find potential new treatments, especially the later part And that's what I have been focused on. I'm more interested in that later stage of Lyme disease, and by connection, or by indirectly in the very early stage, because that early stage could be a critical window that if you recognize what the patient is infected with, that is what strain of Borrelia, and I can, I can get into that as well. And if we can diagnose it very quickly, we may be able to avoid these these later persistent symptoms that are associated with Lyme disease.

Right. How long does that information though take to trickle down to mainstream general practitioners?

That's a very good question. I think, you know, right now we know that there is persistent inflammation. So we may be able to come in. I'll just give you an example. If we know that, there is persistent inflammation and we know the mechanism for that, for which we are— on which we are working, we may be able to come in with anti-inflammatory agents. If we know that there are specific strains of Borrelia that are responsible for the infection that eventually leads to persistent symptoms, we may be able to come up with more effective treatments against those strains. But your question is, how long will this take? It is a question of doing more research and putting in more funding into it and trying, basically having clinical trials of new therapies. That's what it takes. We don't have that to the extent that I think we need right now. So we are, to be frank about it, we are still at a formative stage in understanding these persistent symptoms, what's causing them, biomarkers, and how to address them. This is the frank reality of it that we are just now, and to be honest with you, the research that we've done, we've done it with very little funding, both NIH and through private foundations. It's very little money that's gone into this. If we can increase this substantially to a level, even a fraction of what's spent on HIV, we will make huge strides. And I would say we can, within a few years, we can get to where we want to be. There is no reason why we wouldn't. It's a matter of doing more research and understanding this and, and trying new treatments for patients. If we know that there is an inflammation, and if we know the mechanism, we already have certain drugs on the, you know, that may even be FDA-approved for certain inflammatory mechanisms. We could try those out on affected patients. Why not? And we could see efficacy. And then, you know, patients would have at least additional or would have some treatment strategies that would be applicable at least to a subset of patients. What we develop or what we find may not treat every single patient, but it may treat or help a significant proportion of patients. And that's where we want to get to. And that only comes comes with understanding the mechanism better and biomarkers to recruit the right patients and to actually treat the patients with a therapy, with a treatment that specifically targets that particular inflammatory mechanism. Basically a drug target. We need to find the right drug target. And we can't only focus, I think, on antibiotic treatments. Frankly, this is my—

oh, that was gonna be my next question.

People, people may disagree with me, and there we've spent too long just talking about an active infection. I don't think that's the answer for everybody. There may be some patients, I think there may be some individuals who may be helped with certain antibiotics that is, I'm talking about people who already have symptoms. With early infection, that's different. But people who have these chronic symptoms, there may be some who will be helped with certain antibiotic treatment. But I think the majority of patients, we need to think beyond just purely antibiotic or antibacterial agents. And I have to mention that some antibiotics are also anti-inflammatory. So patients feeling better because they're taking an antibacterial That doesn't mean that it's because of the antibacterial properties of what they're taking. It may be because of the anti-inflammatory and even neuromodulatory properties of what they're taking, because even penicillin has both anti-inflammatory and neuromodulatory properties. So we need to think a little more broadly. We need to really keep an open mind on this and I am of the opinion that, you know, we can't just think narrowly either in this camp or that camp. We need to think more broadly because really the aim here to help patients. I don't care what is, you know, which, who's right and who's wrong, but we need to really address what the patients are experiencing and to address the problem. But I believe that we need to think more broadly about treatment strategies.

Hmm, which is hard to do in New York. You guys have some of the most regulations as far as treating people holistically in the country, as far as I can tell. Other states offer more alternative treatments more readily. New York's pretty hardcore antibiotics.

What—

because spirochetes move out of the bloodstream and into joints and into your nervous system, how does that impact the difficulty in tracking it? Because I know a lot of tests are now testing through urine because it shows actual— I think it's antibodies or something, some type of living organism through urine that doesn't show up in blood tests.

Yeah, I mean, that is, that is the major problem with, with Borrelia, right? So if the organism was if it was easily detectable, we wouldn't have all these problems. The issue with Borrelia is that you really don't— first of all, it moves out of the bloodstream, as you, as you stated correctly, and does it very quickly. So as soon as basically that early stage of infection is over, and basically it moves to tissue, whether it's— it moves out of this— if initially moves out of the skin into the blood, and then from the blood it moves to joints, nervous system, heart, etc. It can go to it. So, so then it's difficult to look directly for the organism through blood tests, and that's why we only look at the immune response. There are, there are tests you can, you can measure it, you can look at for by PCR, but those tests are not very accurate because they don't— the sensitivity of those tests is, is, is low. Specificity is high, but sensitivity is low. You mentioned urine tests. There are a bunch of tests that, that are being offered or people are claiming things about, but there isn't agreement on how sensitive or specific these sort of more alternative tests are. And we need really— that, that's again, we need more research to, to figure out what is the, the sensitivity and specificity of these tests. You can make all kinds of claims about tests that you have, but unless you can validate that test in an independent cohort, preferably blindly, it remains in the realm of sort of unproven tests that some sort of specialty company offers. So we need again more research, we need more collaboration from scientists in academia to really understand how good these— some of these tests are. I've seen some really wonderful talks at conferences that suggest that we may have tests in the future, including urine tests, that will be fantastic. But those are still not, you know, out there or not proven to be sensitive and specific. So there is some time needed to test those. But I'm very hopeful. I think we are getting there. The pace The pace, I think, is too slow for patients. That's understandable. That is unfortunate. That is dependent on how long science takes. Science takes a while, but you can speed it up with more people working on it, with better scientists, and with more funding. I mean, that is what it comes down to. But we are getting there. I have personally seen some fantastic, promising research in this area using very state-of-the-art technology. But, you know, and I have reviewed some of the grants or papers in this, in these areas, and I think there is a lot of potential out there, but we're not there yet. Even from my own lab, you know, we have biomarkers that we've identified. How can we get from here to a test that is commercially available and a patient goes to a doctor and doctor says, I'm going to test you for this? We're not there yet. Why aren't we there yet? Well, part of it is because we haven't had funding to take it to the next stage and actually validate these biomarkers. We've actually published it and we even have IP on it, you know, and we've even had companies, you know, even big companies, biodiagnostic companies talking to us about the potential, the market potential of these markers, discussing various ways to bring this into market. But we're not there yet. We need more funding to recruit more patients, to validate these tests, to see how well they perform in real life, and then put them out there. But I think we are getting there. It is slow, as you well know.

So I know that you're in New York. Did you get to go to the LymeMIND conference at all? The LymeMIND conference?

I did not. I had— I was somewhere else during that conference, but, but I know people who did, and I heard about, you know, some of the things that were presented there.

Yeah, you know, one of the interesting things that I have figured out from going to conferences, Lyme conferences, over the last few years, and I saw it even at the Live Lyme Summit, was a lot of the presenters don't agree They all, which shouldn't be a surprise. I mean, people can disagree over anything, but I thought it was interesting. There's so many complexities coming to the table, some from the patient side, some from the research side, some from funding, some from NIH, some from the CDC, and everyone has kind of a different take. And I was surprised. I don't know why I shouldn't have been, but I was surprised to hear the discrepancy differences between speakers and just realizing, God, we have a long ways to go.

Yeah, that is a problem in the Lyme disease field, that there is disagreement. Part of that, I mean, depends on the meeting that you go to. Part of that is, if I may say, a disagreement between clinicians who see patients day to day, and academic scientists. And there is a difference in the way that they process the information that they have. And part of it comes from that. And you probably noticed in the, in the meeting that, that we, you know, that I met you at, the difference in style, the difference in how scientific information is is basically interpreted and perceived and presented. So, so there is a difference in that. And then there is, of course, you know, disagreements have always been there and do exist in every field. But as we learn more, especially in a stage, in a formative stage like this, where we don't know a lot about something, right? When you don't know about something as much you can make all kinds of speculation. True, right?

Yeah.

And each patient has a filter, you know, based on their own experiences, right? For sure. That information is every symptom. You know, I, you know, had some foot pain lately, and I perceive information about, you know, I read a lot about it, but I'm not an expert on on foot pain at all. So I perceive the information based on what I read online, the papers that I have access to. That is a little bit different from a clinician who sees patients, and again, that is different from somebody who is doing hardcore basic research on that. So there are differences in how we filter information, and we are all biased, right? But what a a scientist, a good scientist does, and that's not trivial to say what a good scientist is, but a good scientist basically needs to put all the information out there and try to see what is the evidence for each of these pieces of information and what is the strength of this piece of information versus that piece of information. A paper— no two papers are equal in the strength of the scientific data that they present, you know. So a paper presenting information on a case report of a patient that came into the clinic is vastly different from a study that looked at 100 patients and took, you know, 8 years to do. We're talking about different— but sometimes at some of these meetings, a case report is put next to or is presented with the same level of certainty as a study that was done on 100 patients that had a control that was done in a very controlled setting that may even have been blinded. So we have to— and, you know, patients, you know, they're not trained in this. It's clear. And many clinicians are not trained in that way of scientific thinking. So some of the meetings that we go to has clinicians or even some patients would talk and they filter what they basically have been exposed to through their sort of own experiences and present it. There is nothing wrong with that, but there is a difference in the level, the strength of the science that is presented at some of these meetings. And that's something that I think we have to keep in mind and, and be cognizant of.

Well, and do you think that that like chronic fatigue syndrome is in a sense an epidemic? Are we in an era of chronic fatigue syndrome and associated illnesses? And historically, has this happened before where you just have a ton of people who— I'm generalizing— have chronic fatigue for no reason?

Well, I think what we do know that is that there is a significant number of people who have this condition. I'm sorry about the noise, this is New York City.

Welcome to New York, I know.

This is how it is, that's how we live here. We know that how the rate or the prevalence of frequency of this has changed is not well understood because first of all, we haven't had biomarkers to track The diagnostic approaches haven't been the same, and in fact, we don't have the same— we did not have the same understanding as we do now. The diagnostics of it are purely clinical, so we don't know how the prevalence of this has been changing from 100 years ago. We don't have a tool to do that, which is why it's so important to have a biomarker so that we can— if we had a biomarker, we could even go back in time to 50 years ago and study stored blood samples. Imagine that. And we could know for sure whether the rates are changing. For example, in the case of celiac disease, which is an autoimmune disease of the gut, and there is a very good biomarker for, we can go back 50 years ago and know that the rates of celiac disease and autoimmune disease have been increasing. But we can't do that for, for for chronic fatigue syndrome, or for example autism, which we don't have biomarkers. It is a— but we do know that it is a significant problem. We don't— we do know that, that there is a huge health impact. We know that there is an economic impact of chronic fatigue syndrome, of the chronic symptoms associated with Lyme disease. We do know that. So it is It is clear that we need to address it. That's clear. And we need better tools to diagnose patients so we know how it's changing through time. And we need tools to basically recruit patients into studies to basically study how we can treat patients properly. But I agree with you if you're alluding to the real importance of the fact that there are a lot of patients who are suffering, who are really experiencing this. And you mentioned chronic fatigue syndrome, and it's very broad how patients are, what the experience of the patients, it goes from something that's minor. And people often think of chronic fatigue syndrome as something patients are just tired, but it ranges from fairly minor to extremely severe to the point that the patients are so debilitated that they cannot get out of bed. So there is a huge spectrum of the severity of symptoms, and it's very possible and very likely that the mechanisms at work for the very severely affected patients are different from the ones who are not as affected. And so, so we need to study them differently. We need to separate them. We need to understand what the mechanisms at work are. We can't put them all together and try to study them as a whole or come up with a treatment and say, we we got to just treat everybody the same. No, it's not going to work. It's very unlikely that that will show any efficacy in a study. So if you have a drug today and you say we're just going to recruit chronic fatigue syndrome patients, it's very unlikely to show efficacy unless you say I'm going to do it based on severity, or even better yet, I'm going to do it based on a certain biomarker that this drug will specifically target.

Okay, so I have 2 questions as our time is coming to an end. One, I didn't ask you at the beginning, but how you got into this whole field of Lyme disease. What, what brought you to this niche?

Yeah, you know, I have always been interested in spectrum, spectrum conditions. That are very difficult to study and for which we don't have biomarkers. And patients sort of feel left out, whether it's certain food sensitivities or it's these chronic symptoms that are not really addressed adequately by the clinical community. I mean, patients go to a doctor and Often the doctor is not trained or doesn't know how to treat the patients, and they usually, you know, they're said, I don't know what you got, goodbye, right? So I've always been sort of attracted to studying these conditions because we know that patients are suffering and their symptoms are not addressed. There is a lack of funding for these, so they're difficult to study. Patients also feel very left out. There is, in fact, a psychological toll to these symptoms, a very serious one, to these sort of unresolved symptoms that patients are experiencing. And I was originally trained in, as you mentioned, proteomics and bacteriology, and then I did my postdoctoral fellowship in neuroimmunology, and that's when I got really interested. I started first working at a medical school setting and coming into contact with sort of medical issues and patients and more to the role of the immune system in neurologic and psychiatric symptoms. And that's how I got into it. And then I did more work in the context of gut immunology, that is the immunology that takes place in the gastrointestinal symptoms, which is so important and is so essential to health. The gut has its own separate immune system, its own separate nervous system, and what's going on in your gut really interacts with the, or contributes to your general health, and even interacts very heavily with the brain. So what goes on in your gut, you know, we say I have a gut feeling, it's not far from truth. All. We know that there is a huge— so I got really interested in gut-brain interaction, the role of the immune system in, in basically the nervous system, the proper functioning of the nervous system. And initially I, I got interested in Lyme disease because the, the laboratory I was working in became interested in patients who who were basically experiencing symptoms in response to a vaccination for Lyme disease back in the '90s. Oh, okay. Yeah, so there was a vaccine back then. There is no vaccine right now, as you know, but there was a vaccine, Limerick's, and there were patients who were experiencing symptoms. And the early research that I did indicated that there may be some cross-reactivity of the immune response to the vaccine against the nervous system. And that was a sort of an early research that we did that we didn't continue on for lack of funding. And that vaccine was eventually withdrawn for various reasons. But, but that's how I got into it, really. How does— and I was very interested early on, and I still am, on how the immune system makes mistakes takes and initially attacks an infectious disease or even a vaccine, but then turns its attention to the body itself. And there are autoimmune diseases like this. So we have a disease like— called— that's caused by Campylobacter jejuni that is an autoimmune disease. It's an infectious a disease that eventually attacks the body's own nervous system. And so there are cases like that. And I was also studying sort of another autoimmune disease called celiac disease, as I mentioned to you, where there is a very robust immune response to a food that we eat. So immune responses that go awry basically and start attacking the body itself. Itself is how I got into Lyme disease. And we were— I was able to get NIH funding early on. And that's how I ended up staying. I actually intended to go into industry. But then I started getting funding and I became more and more interested in academic research. And then I started my own lab and the rest is history.

Where do you think we're going to be at in the year 2040? 2020 with Lyme disease treatment as far as public? What is the, the person who's going into their general practitioner and/or infectious disease doctor in 2040? What do you think treatment is going to look like compared to how it does now?

Well, I think, I think what's going to happen first is that the person who goes in with Lyme disease, with acute Lyme disease, even if it's very, very early on, is going to get diagnosed very accurately. Accurately. So there is not going to be any patient who's going to be left out undiagnosed. We're also going to know if patients have persistent symptoms because of Lyme disease. That individual is also going to get accurately and very quickly diagnosed based on the tests that become available 20 years from now or are available on the market. And we are going to know the mechanism by which these persistent symptoms cause— are caused, and there is going to be a treatment. So quick diagnosis, treatment, and resolution of symptoms. I think it's really quite rational and reasonable to think that we will have much better diagnostics and actual treatment for the various manifestations of Lyme disease in 20 years. Time. So very, very optimistic. Yeah, you're not convinced perhaps, but, but I think we can get there. I think because of what's— what I've seen being done by patient advocacy groups, by people in the field, increased funding coming in, more research being done, if the sort of the curve keeps going the way it is and the pace keeps picking up at an increased acceleration, then I think it's, it's completely reasonable to think that that will happen. 20 years is a fairly long time. And so I think that we will get there. So I hope I'm right.

Yeah. Yeah, me too. It's interesting. I've been asking that question to a lot of people and the response The responses again are all over the place. Like, oh, it won't even be a big deal by the time 2040 comes around. And I think the thing, you know, the fact that it attacks the neurological system or your nervous system, the fact that diet and nutrition and your immune system play a really big part in it is another factor because that's something a lot of people aren't willing to address.

You make a really good point and it's something that I, you know, we should probably mention during this conversation that many patients undergo long-term antibiotic treatment, and that has a huge impact on the— what's living in your gut, the microbiome. And increasingly, we are understanding the huge significance of the microbiome to health. So, and, you know, antibiotics and diet are the most important— there's research that has shown this clearly— are the most important contributors to the health of the microbiome: what you eat and antibiotics. And if you're needing to take antibiotics for a long time, you can imagine what kind of thing is happening to your, to your gut microbiome, and that is going to have an impact impact on the symptoms that the patients are experiencing. So we need to study that as well. And there has been virtually no study on that aspect of what really is happening with Lyme patients. The antibiotic treatment aspect of that, which is something that some patients may need, but many patients may undergo, and we're not really addressing what's the— what the relevance of that antibiotic treatment and what it's doing to the body with regard to the symptoms that the patients are experiencing. Yeah, I think that's really important. We really need to study that part, and this is something that I'm really pushing towards, understanding the relevance of the microbiome to the, the chronic symptoms in Lyme disease. Yeah, we got to go after that.

Yeah, and that's what I see, you know, just from a patient perspective, is the people who are getting better better are doing everything. They don't all do antibiotic— antibiotics, but predominantly. But in addition to that, it's nutrition, it's supplements, it's alternative treatments and high-dose supplements. And it just seems to make a big difference.

Yeah, I mean, patients are trying everything because, again, that's, that's what they have to do. And some things are working for some patients, The, you know, of course, diet, sleep, reduction of stress are so important, we know, to the health, to the general health. So you may be able to address many aspects of the symptoms that patients are experiencing just through addressing these issues. And there are doctors out there that rightly are addressing these issues because, you know, we don't live in a bubble bubble. We are a product of our genes and everything that we experience. So we may have been infected with Lyme disease in the past, but we're also working, we're sleeping less, we are, you know, are more stressed out, we are checking our emails all the time. These cannot be ignored. So, you know, again, when you're doing very well-controlled research, you have to take all these into account because Stress, lack of sleep, these are important issues. And I know physicians who are actually addressing these in chronic fatigue syndrome and chronic Lyme patients. And it is being effective in the case of some patients. So you have to, you know, or some patients are addressing these themselves. And gut issues, there hasn't been a very good study or any study in the context of Lyme disease. But I have been working on chronic fatigue syndrome and I know that 60-70% of patients with chronic fatigue syndrome also have gastrointestinal symptoms at a— at a— this is a significantly higher proportion compared to the general population. So, so that by itself tells you a lot.

Yeah.

Wow.

Thank you so much for being here with us today. I appreciate your time immensely.

It's my pleasure. It's good talking to you, and I hope this was helpful to, to you and your audience.

Yeah, thank you so much.

My pleasure.

Hi guys, I want to let you know about a book I wrote called Little Bite, Big Trouble, and I'm gonna read a review that recently came in. This is from Carolyn, and she says, thank you so much for writing your book. It has become the means by which I have explained Lyme to my 4-year-olds. They ask for it to be read as a bedtime story over and over again and love that the mama birdie does yoga and juicing like their mommy. I can't thank you enough for writing this book. It has helped my family so much. You can find it today at amazon.com. Little Bite, Big Trouble. Disease is contrary to life. Therefore, wherever disease exists, life must also fight to exist.

Good job fighting, Lyme fighters! Keep it up. We'll see you next time.

LymeVoice contains general information about medical conditions and treatments. The information is not advice and should not be treated as such. K, Lincoln? K. The medical information on LymeVoice is provided as is without any representations, warranties, expressed or implied. Okay?

Okay.

Lion Voice makes no representations or warranties in relation to the medical information on this podcast. You must not rely on the information on this podcast as an alternative to medical advice from your doctor or other professional healthcare provider. If you have any specific questions about your medical matter, you should consult your doctor or other professional healthcare provider. And you, you consult your parents. Okay?

Okay.

If you think you may be suffering from, from any medical condition, you should seek immediate medical attention. You should never delay seeking medical advice, disregard medical advice, or discontinue medical treatment because of information on this podcast. Got it, Lincoln?

Got it.