Nirala Jacobi:

Welcome back to the SIBO Doctor Podcast. I'm your host, Dr. Nirala Jacobi, and my guest today is Dr. Paul Anderson, and he's no stranger to this podcast. Dr. Anderson is a recognized educator and clinician in integrative and naturopathic medicine with a focus on complex infectious, chronic, and oncologic illness. In addition to three decades clinical experience, he also was head of an interventional arm of a US NIH funded human research trial using IV and integrative therapies in cancer patients. He founded Advanced Medical Therapies in Seattle, Washington, a clinic focusing on cancer and chronic diseases, and now focuses his time in collaboration with clinics and hospitals around the US and other countries.

He's had numerous teaching positions in medical school and has co-authored a few books, including Outside the Box Cancer Therapies and also Cancer: The Journey from Diagnosis to Empowerment. He's a frequent CME speaker and writer and has extended his educational outreach, creating an online CE website, consultdra.com, and Advanced Applications in Medical Practice conferences. AAMP is dedicated to bringing next-level learning to healthcare professionals to enhance their knowledge in clinical skills in CME-approved format, and I highly recommend practitioners listening in to check out the AAMP.

Welcome back to the SIBO Doctor Podcast, Dr. Anderson. It's so great to have you back.

Paul Anderson:

Thank you so much for having me again.

Nirala Jacobi:

I'm so thrilled to be speaking with you again because I consider you one of the foremost physicians who continually expand our knowledge of biochemistry, genomics, immunology, and all things chronic disease. I mean, you were one of the first ones to talk about methylation before anybody talked about it, and I've been to many of your seminars, and I just want to thank you for your valuable insights in how we manage our chronically ill patients.

Paul Anderson:

Well, thank you. That's what I put all my time into, so it's good to know it's working.

Nirala Jacobi:

Oh, it's working, yeah. So I'm a SIBO specialist, and I always aim to find the underlying cause of SIBO and other functional gut disorders in my patients. And sometimes it's easy, and sometimes it's not so easy, especially when we're dealing with potential viral reactivation or other issues that theoretically originate outside of the digestive tract. So I wanted to have a conversation about chronic viral infection and viral reactivation syndromes and their impact on gut function. So let's start with the basics about common viral infections and how these often go undetected.

Paul Anderson:

Yeah, I think that's an excellent place to start. I think that there's a couple of really critical things with chronic viral infections for the purposes of the discussion that we're going to have with respect to chronic illness and whatever specific chronic illness we want to get into. And the first thing is that what becomes confusing, and what people sometimes get mixed messages from their healthcare providers about, is most of the virus families, or the specific viri we're going to talk about, are ubiquitous in nature and in humans, and everybody tends to be exposed to these things at some point in their life. So that leads some of our healthcare providers to say, "Well, they're so common, and everyone's exposed. Why would one person have a problem with it that would create a chronic illness and another person, or the majority of people, don't?"

And the distinction there is that, while probably over 95, maybe over 99% of people, get exposed to a lot of the things we'll talk about, there's a subset of people, for either immune reasons or maybe more complex reasons, that the body and the immune system develop a more symbiotic relationship with the virus, and so the virus is allowed to reactivate, either due to a specific trigger or due to the general health of the patient, whereas the majority of healthy people, this doesn't really happen.

So you always have to be careful in characterizing these things, that they tend to be very different than their acute infectious versions, which are very unique, and their chronic expressions are often very hard to pick up on diagnostically, and so they masquerade as a lot of things.

So I always like to start there with people because first thing you usually hear from your doctor is, "Well, everyone's had that virus, and that can't be your problem." And then the next thing is, "Well, your symptoms don't really match what that virus normally presents like, so it can't be that virus." And so we have to move our minds beyond that in order to understand, I think, viral reactivation.

Nirala Jacobi:

So, and when we talk about common viruses, would you say that that's mostly the herpes viruses that most of us have had an exposure to from very early, maybe, perhaps, even in utero, in terms of human herpes virus simplex, or EBV? And those types of viruses tend to be pretty much, like you say, ubiquitous in everyone. And so that's something that I'm dealing with a lot with people that have had, obviously, infectious mononucleosis... we call that glandular fever here in Australia... and they basically have, like you're saying, the initial infection is very different from what they're dealing with much later on, and how this can really impact their health, not just digestively, obviously, but also on a fundamental level. But the common viruses, would you say that's the main ones?

Paul Anderson:

Yeah. That family, the human herpes virus family, contains at least eight well known virus that affect humans and many other animals, too. And the ones that we think... When you hear the word herpes, people always think of herpes simplex type one and two, either the oral or the genital form, but those two have a number of cousins. And so, for instance, as you mentioned, Epstein-Barr virus is one of those. The varicella, chicken pox, virus is another one. Cytomegalovirus. And there's a number of others.

In my experience with people with chronic illness, that family is... It's the first place I look, anyway. It's the most common. And I think part of it is because they're so universally exposed to us, as humans. When you have a virus, your immune system marginalizes it, but it never fully kicks it out of your body, so we all carry little bits of these things, and I think it's what makes that family easily reactivated in a chronically ill person.

Nirala Jacobi:

So let's say somebody has the typical... Oh, well, let me ask you. So what would you say are the classic clues that point you to thinking that somebody has a viral reactivation happening?

Paul Anderson:

Well, I think those are almost always clinical tells or clinical clues that we look at in people, and there's really two groups of people that we deal with in this respect. The first would be a patient we already know, maybe, has struggles with certain chronic issues, and possibly they've been doing pretty well, and they're feeling pretty strong, and maybe they have some stressors in their life, or they hit a rough patch, or even, maybe, they get the flu, or they get COVID or something like that, and after that, they're never the never really the same. Their energy goes down, maybe they have more pain, possibly they're sleeping more or less than normal, and any number of things that can be signatures of those virus. So if it's someone we already know the pattern, it's a little quicker trip to saying, "Let's at least take a look and make sure you haven't reactivated one of these common virus."

For a patient that we've never seen before, the people that I'm more likely to be looking for those virus in are going to be people who have had either poorly resolved problems with fatigue or pain, for instance, the chronic fatigue type picture or fibromyalgia, people who are never better since a big stressor. That could be a car accident, a surgery, another infection, like we talked about, or any number of things. But they do tend to cluster in these areas of energy, sleep, different types of pain. Some people, it's joint pain. A lot of people, it's more nerve pain. Can be headaches, et cetera.

And then something else that crosses over with your population a lot that I was really glad you wanted me to talk about this topic is now we're finding that some of these virus create a lot of trouble in the GI tract as well. And that's something just in the last, I don't know, five to seven years I've been aware of and started looking for in my GI patients. And what's curious with them is they may not have the classic fatigue or sleep issues or body pain, but they may have an exacerbation of their GI symptoms.

Nirala Jacobi:

Yeah. That's what I'm finding. And what's really interesting to me is that there isn't a huge amount of research yet. I mean, it's possibly coming now with a lot more research since COVID into generally chronic viral illnesses and long COVID, and we'll get to that in a moment, but one of the interesting hypotheses was that Epstein-Barr virus, who... Well, the virus, in its latent phase, tends to be hiding out in B cells, but when it gets reactivated that there is some potential for actually infecting the vagus nerve. So that's a hypothetical theory that's been put out there, but it would make sense that that is one of the ways that it can affect the digestive tract because, as we know, the vagus nerve is so involved in multiple GI functions. What are your thoughts on why people develop GI symptoms with these chronic viral or reactivation syndromes?

Paul Anderson:

Yeah, I think that there's a number of potential reasons. And what you just mentioned with vagus nerve involvement, because that's so critical to carry the parasympathetic fibers down to our digestive tract so that it actually operates properly, it's a pretty big deal. And like you said, it's a theory at this point, but the one thing that I always try and relate to patients about this family of virus is that, generally, they really do like nerve tissue. They love to hide out and hang out in the nervous system. And this is one of the reasons why, if someone's having nerve pain and it's related to that, it can be very severe because the nerve is actually affected. So it makes complete sense that you could have something like a cranial nerve, like the vagus nerve, be involved because number one, it's so long. It's a very long nerve that does a lot of things. And it's in proximity to places like the GI tract, where some of this virus will hide out.

I think that the other side of it with these virus is, as you mentioned, there's not an excessive amount of hardcore research on them, but we are starting to see more correlative research between, for instance, the cytomegalovirus, Epstein-Barr's cousin, and a lot of inflammatory GI pathologies that will go on. And sometimes another thing will happen with people, where we might be treating them for, we might perceive, or their tests are they have an active Epstein-Barr or cytomegalovirus going on. We assume it's systemic, we start treating them, and we get a lot of gastrointestinal side effects. And now what we understand is that's probably the immune activity in the gut affecting the gut cells that are holding onto the virus.

Nirala Jacobi:

Can you elaborate on that a bit more? Because that's fascinating, that we're treating, we are using antiviral therapies, and what you're saying is some of the epithelial cells that may be infected or the enteric nerve cells that are infected actually are reactive to treatment for virus in those locations?

Paul Anderson:

With some of our new knowledge that the GI cells are much more of a reservoir for, certainly, cytomegalovirus and probably Epstein-Barr, too, than we ever thought before, because no one thought to look there for them, you could imagine if... Most of the therapies we do are going to be oral, and so they have to go through the GI tract. So here you think that you are... and you probably are... treating a systemic viremia, where the virus is reactivated, but I have noticed now, looking backwards at patients, if we had a big digestive reaction to the things that we were using to treat the virus, sometimes we would blame, "Well, maybe it disrupted the flora," or something, but now, I'm starting to see a pattern where it's probably actually the killing of the virus inside the cells in the GI tract and then the GI tract trying to respond to that immunologically. Yeah.

Nirala Jacobi:

And what are some of the most common symptoms you see when you start to start treating these viruses? I guess a bit of a die off reaction?

Paul Anderson:

Yeah. It's akin to die off. So a classic die off, we think of a lot of times with bacteria, where most of them live outside of our cells, and their death creates a whole bunch of chemistry that's very disruptive to the body, so it's almost like a poisoning. In the case of these virus, they discreetly live inside your cells. So if they're in my digestive tract, they're going to live inside my GI cells and replicate in there. So then if I have antiviral therapies of whatever they are that actually get there to those cells, they will start to either stop replication of the virus or directly give the attention of the immune system to the cells where those virus live, and then the body will have an immune reaction to that going on.

So if that's in your gut and it's with your gut immunity, your gut immune system, depending on how your gut GI health was prior, you can see things like pain syndromes, such as cramping and that sort of thing. I've seen exacerbations of both diarrhea or constipation. And then a number of other things, but they tend to be around bowel function and pain if that's actually going to be what flares up.

Nirala Jacobi:

That makes a lot of sense. I mean, we know, or some of the research that I've reviewed is in Epstein-Barr virus and in conjunction with H. pylori having more of a carcinogenic role. And we don't really see much else other than the colitis that you mentioned with CMV, that I've looked at, but with EBV. And I just keep coming back to that because I just think that it is often a player when you've exhausted other potentials and you start looking at labs, which we'll get to in a moment, that this may be, really, a bigger player than we ever thought in terms of also chronic SIBO and people that can't clear SIBO because it's really affected their enteric nervous system or their vagus nerve.

And this is the hidden thing that I want to get to is just how do we assess this, and how do we understand if that's what it is? Do you always see this pain syndrome that you talk about? And I do think that chronic fatigue and exercise intolerance or exertional fatigue and those types of more chronic fatigue syndromes symptoms are pretty common with people that also fit the criteria of having a potential viral reactivation. So yeah, I just wanted to mention that, that there isn't a whole lot in terms of real causality in terms of research of SIBO. So it's still quite hypothetical. So I just wanted just to mention that.

Paul Anderson:

Yeah. I do think it's always important to let people know when we're going off our best assumptions and clinical information. But I think part of it, too, is that, until very recently, these virus were so... they're so ubiquitous that, even in the research community, it was assumed that they probably aren't the problem. It's probably something else. So if you don't look for something, you never find it. You'll never do research on it. And so in my estimation, it's really only been since some of the chronic GI connections to CMV started to be made that now people are opening their minds back up to that.

And you mentioned in a little bit, we'll talk about COVID. There's actually some almost brand new research around this viral family and specifically GI symptoms in post-COVID and a number of other things. So I do think people are... It's on the radar now in the research community, which, hopefully, in 10 years, we'll we'll know a lot more.

Nirala Jacobi:

Yeah. In 10 years, we'll know what we should have done 10 years ago.

Paul Anderson:

Right now, we just have to try and help people, but yeah.

Nirala Jacobi:

Yeah. Exactly. That's great. Let's see. Yeah. I just want to... because I know sometimes when we have these conversations and we're practitioners, we can lose the listener. This is why I always try to bring it back to we're talking about the gut and how this may relate to you. And if you've had SIBO and you are somebody who is chronically fatigued and you have a lot of myalgias or muscle aches and pains and no one can seem to find the answer as to why you continue to relapse SIBO, this may be something to look into is the discussion we're having here.

The other thought that I wanted to bring up before we go into, "Well, how do we assess this?" is this notion, or this concept, that we are all carrying so much more burden. And this also seems to be, when we talk about viral reactivation, there are certain triggers for viral reactivation. And you mentioned stress, and there are a few others, like having a big toxicant load, for example, having more heavy metals, having more stuff on board that messes up your machinery, particularly the mitochondria. And then we can't really launch a proper immune response to some effect. Can you talk a little bit about that?

Paul Anderson:

That's a really critical thing for people to wrap their heads around, which is... And it goes back to that original problem we run into with most healthcare providers who will say, "Well, everyone's had exposure to Epstein-Barr and probably all of the other ones." The problem that occurs is, under normal healthy circumstances, when your body is operating properly and your resistance is good and your immune system has a normal relationship with your body and the outside world, even if you've been exposed and you have some of these virus left inside of you, that they don't do anything. They're very quiet. And that's what we want. We want to live that way.

Why would they be more common in people, say, with harder to treat SIBO or chronic fatigue syndrome or somebody after a major stress or trauma in their life or any other thing? Well, it's because there are so many things in our body that affect our immune system's ability to keep all these virus at bay. It's like an orchestration that goes on, and if we start to diminish the ability of the immune system to do its job, then the virus is just doing what it does. It's opportunistic, and it'll start to replicate and become more of a problem.

And in working with patients with chronic illness, I will usually look at a few very big areas that are... they're the first places to look, anyway, for this immune stress, if you want to call it that. One area, like you mentioned, is toxicity and exposure. We're all exposed to a lot of toxic things, but some people are more sensitive than others. One of the worst, in my experience, has been the mold toxins, mycotoxins, because they actually are known to diminish your immune function very fully. Another area is cellular function, though, and this is the connection to... You mentioned the mitochondria. Some people have more stressors on their mitochondria, which help to run your cell, give it energy, et cetera. But then there's other things, like we talked about at the beginning, with methylation problems and genetic issues with maybe you don't use your nutrients the way everyone else does. And you put that person under stress, they can't respond as well.

There's other things that come up. Resistance factors in the body. Our last discussion you and I had was about biofilm. That's a type of resistance that can definitely do this. But there's a number of other things that relate to things like toxins, et cetera. And then even stressors on your hormone system, the endocrine system, can certainly create a milieu in your body, where the immune system just can't keep these guys at bay.

So normally, and you used the example earlier, say, in the SIBO patient, where you have your more classic, standard SIBO patient, and they respond to treatment, and they progress through like you're thinking that they should, and then you get another patient, and they have classic signs and symptoms, but either they never respond fully, or they have a lot of other parts of their body that get involved, such as more fatigue than normal, more pain than normal, that sort of thing, those are the people where, often, the immune system has been stressed to the point where it can't keep these virus under control. And then they poke their little viral heads up and start to replicate inside of us.

Nirala Jacobi:

Mm. And in the last year or so, I've had at least 10 patients who I've gone through the gamut, treated them for SIBO, discovered mold, thought that was the underlying cause of their SIBO, treated it for the... They've gone through all this treatment, and some will improve, some will improve greatly, and some just are stuck in this chronic fatigue state. And so this is what also prompted me to do a bit more research into these chronic reactivation syndromes because I think this, as practitioners, it's always our job to not get stuck on a diagnosis. I always tried to not hang all of my diagnosis on the SIBO hook. It's like, "Why did this happen? Why is this happening? Why is that happening?" And so that's, I think, what makes us good clinicians, is that we keep learning about different things that interact with each other and how we can also help to get to the next level for these people.

So I have at least a handful right now that I think are in this specific category of post-mold, they have cleared up everything. Yes, they have CIRS, or chronic inflammatory response syndrome. Yes, they have the HLA-DQ pattern that corresponds with that. But now what? Is this now just a viral issue? They continue to have digestive issues, even though it's not SIBO. I'm working on their microbiome. So it's been a really tough nut to crack actually. So yeah, that's where we're at with that.

Paul Anderson:

Yeah. I would agree.