Nirala Jacobi:

Welcome back to part two of the SIBO Doctor podcast, and let's jump right back into it. So moving into diagnosis, I know that ... I took an immunology class from you many ... or a course that you had online, a fantastic course, and I always have that as my handout in terms of how to diagnose this, but the fact is, it's very difficult to diagnose reactivation of EBV, for example, simply because we don't have really good, solid markers that correspond with the viral reactivation, or do we have anything new to report? Is anything that's going to help us?

Paul Anderson:

And that truly is one of the frustrating clinical aspects of, especially viral problems and viral reactivation. Because if you take this HHV, the human herpes virus family, where CMV and Epstein–Barr live, because people have been generally exposed to these things, and then if you look at immune memory, like immunoglobulin G, which is a memory immune protein, it could be there and elevated simply because you at one point had it. For instance, if you have ever had mono. For a number of years, your IgG will be elevated.

There is an acute immune protein called IgM, like Mike, and in the gut, there's one called IgA, like Alice. And those are a little more sensitive for diagnosing an acute spike. But the problem is, if your body has had these virus before, they may or may not convert and make those immune proteins anymore. So there's a couple of issues around it.

One of them is, if you absolutely need a 100% certain diagnostic test, it doesn't exist. Now, you could say that for almost everything, but with these chronic viruses, you have to, in my mind, do a couple of things, and I've done this with people for a long time. And I'm basing this not just on what I see in research and what I see from the laboratory world, but the feedback you get from patients of looking at the pattern, treating it and seeing if they get better, in my mind with these, you always have to clinically correlate what you believe you see in the labs with their history and their presentation

And then the real proof is if I intervene and I do something to help with their viral immune response, or in that neighborhood, does it make a difference in their case? Does it actually help out? And in most cases, there is a cause and effect relationship that's pretty close. And that helps with this ambiguity around the laboratory testing.

Now, there is a phenomenon in lab testing for the memory immune protein, the IgG, G like George, where there's a number of kind of technical names for it. But basically, it's sometimes that will be elevated, not because of an old infection, but it will go up if you have a reactivation. So there are some patients we have where maybe we tested them and we did the IgM and the IgG a year ago, five years ago. And it was kind of average. No big deal.

They have this flare up and we do it again. And the IgG is two or three or four times higher. There's actually research that shows that that is an indication of an acute exposure. And it's atypical because the IgG shouldn't do that technically, but it's because the body has been holding onto the virus for that whole time. And so it'll spike as an acute measurement.

Now, with Epstein–Barr, we have a few other tests in the immune globulin world that can help with reactivation. They're still not perfect, but there is a test called an early antigen where it will rise in a chronic reactivator in 90% of cases. And depending on where you are in the world, they call it an EA IgG or an EAD, like dog. It's the same test.

So that's a little helpful there, but with cytomegalovirus, you don't have any of that. They haven't developed the testing that far. So with that, you literally have to look and look at the burden of the IgG. And my experience has been if it's elevated enough and they have symptoms, it's worth investigating.

The best part, if there's the best part about all this ambiguity is the whole family, so it wouldn't matter whether you had EBV or CMV, or even one of its cousins. The treatment is very similar or exactly the same. So the intervention is going to cover whoever is there in the family anyway. And then we just, you clinically monitor the patient, see if they either flare up or if they start to have changes in symptoms when you address the virus. And then that's really your confirmation.

Nirala Jacobi:

And what about other sort of patterns of other standard blood tests that we order? I've heard from other practitioners about low white count, high white count, lymphocytes, low ferritin, those kinds of other biomarkers that are not specific to viral illness but can give us an idea of potential immune states. Is that something you utilize as well?

Paul Anderson:

Yeah. All of those things are very useful for the big picture. So if you look and the classic thing that most people are taught is if you have a patient's history and they've always had bottom of normal white cell count, or even a little bit below normal, just persistently, those people very commonly do have a lot of chronic virus that they're carrying around.

You classically kind of look for a lymphocyte elevation with virus, but the problem is with these chronic ones, the body essentially gets tired of the virus and stops reacting like it would if it was an acute viral problem. So sometimes that doesn't always work out, but it's worth looking for. Then there's inflammatory things that sometimes will show up, especially if the virus is very active. You mentioned ferritin, ferritin will go up because of inflammation.

And the other thing on the white cell count is the neutrophil to lymphocyte ratio will, if you do just a basic ratio of the neutrophils over the lymphocytes, is a particular number there. The higher that value goes, the more likely the person is inflamed and probably infected. But these are all kind of non-specific. There are also these PCR tests. And now I think with COVID, everyone's heard of PCR tests, for better or worse, but those are actually looking for the nuclear material, usually to a virus or to something. The upside is, they're a little more specific than the immune protein testing that we use mostly. The downside is that they will pick up, they will give you a number for dead virus the same as live virus. You can't be doing PCR testing super frequently if you're treating someone.

Because I've literally seen people where all their symptoms were gone and they redid their PCR and the viral load was still very high, but it was all dead virus. They all have a clinical place and a meaning, but none are perfect. And I think that these other non-specific labs, like looking at white cells and maybe looking at the families of white cells and inflammatory markers, such as ferritin, et cetera, those are all good clinical correlation to say, this person's got something going on. These are not specific, but we have this plus indications in their testing for Epstein–Barr, cytomegalovirus, or both. And so it makes a therapeutic trial reasonable to go into.

Nirala Jacobi:

Okay, we've come to the point where we have to talk about COVID because COVID also affects the gut. EBV and CMV and these other herpes viruses have been with us for a long time. They stay in our body. We can't get rid of them. What's the deal with COVID, because it's a really different type of virus, and does it affect the gut? And I have seen some studies in retention of COVID and changes in microbiome, et cetera. So let's dive into that end of the viral pool.

Paul Anderson:

Well, we all knew we'd get here. I think there's a whole host of ways that the gut can be affected, in my experience, with COVID patients. So during the last few years, while COVID has been as it's been, I've had a fairly large number of patients that fell into two categories around COVID.

One were people I was consulting with their doctors and the patients were in the hospital. And that was for very specific reasons that we don't need to get into today, but it had to do with some hospital procedures that may be helpful with COVID, but the other group were people that had acute COVID. And I wasn't planning on having acute COVID patients, but there were just a lot of them and that's how it worked out.

So I've had more experience than I probably thought I was going to with COVID. And there's a couple of things I think with COVID. One of them is, and this has actually been known since the very first Chinese data from 2019. And that is that the sicker the COVID patient was, the more other infections would pile on, you could say, or reactivate. And I've actually done podcasts just on the topic of COVID and co-infections, and I did a research review, which now is a few months out of date, but it's still pretty recent. And just the papers on co-infections along with COVID making COVID worse, there were over, I believe, over 30, if not over 40 papers on infections in COVID. And one of the families of infections that is most represented in that research is the human herpes virus family.

And so Epstein–Barr has the most papers because it's the one everyone looks for. And it turns out that COVID appears to be able to activate Epstein–Barr in people, even if they were not chronically ill before. So they could've been very healthy before and they come out the other side of COVID and they're not healing. One of the possible causes is Epstein–Barr. And now they're saying cytomegalovirus.

The other problem where there's a crossover with COVID and the GI tract is in ... and these, it made sense, I think, to researchers right away to say, gee, we know from other viral infections, if you get really sick, there are opportunistic bacteria, parasites, viruses that will pile on. So we should look for these. So really, all around the world, people started doing this research, and in all of these papers that I've read, whatever they looked for, they pretty much found.

So most researchers weren't looking for every bug in the world, they would do viruses or parasites or something. And every paper found something they were looking for. Well, a number of the papers talk about permissive activation of digestive system pathogens. Most of them were parasites and fungus, but there's also some bacteria and other things. And that's simply because of the immune reaction to COVID in the first place.

So much like an Epstein–Barr reactivation, as you know, and people have probably heard who are listening, in our GI tract, we try to mostly have the good bacteria and the good flora, but we also have a little bit of the bad guys. Well, it turns out that COVID is a situation in your body that can shift your microbiome and maybe even small amounts of parasites or other bad guys that were not a problem before we'll start to multiply.

And so that's another big correlation to the COVID gut connection, which I think is very important for people to remember if they're having persistent GI problems in the post-COVID world.

I literally just did a podcast yesterday where I talked about post-COVID markers, and there was a paper I found that actually looked at what they call gastrointestinal post COVID. So I want to make sure we talked about that too. So a bit ago, I mentioned this new study that I literally ran into while preparing for a podcast that we did yesterday. And the podcast, the major topic was about post-COVID syndrome and some of the research that's coming out.

And as we've seen in other studies and would be expected, Epstein–Barr virus is associated with worse post COVID, and in the general sense, but then as I was reading this study, which was published just a couple of months ago, March 2022, in the paper Cell, they also had a section which they didn't advertise, but as I was reading it, they have a gastrointestinal specific post-COVID syndrome.

And what was very interesting was that in the general post-COVID patients, it was Epstein–Barr that seemed to be creating some of the immune problems, but in the gastrointestinal symptom oriented post-COVID syndrome, it's actually cytomegalovirus, CMV, that they found that was involved in the dysregulation of the T cells, which are responsible for your cell mediated immunity. And they found a very high relationship between gastrointestinal symptoms in post-COVID patients and the cytomegalovirus infection.

So it kind of goes right along with what we were saying earlier, where if we have a general, say a chronic fatigue patient or a pain patient and its systemic symptoms, a lot of time that can be Epstein–Barr. And if we have a chronic gastrointestinal inflammatory problem, a lot of times that's cytomegalovirus. And it appears that in post COVID, it's following that same pattern. And this is something I would've maybe guessed, but I didn't know anyone actually looked into it. And this paper's quite wonderful, actually, for that.

In general, on COVID, the association is more with EBV, but in what they're calling gastrointestinal long COVID, the association is with cytomegalovirus. So it kind of follows the pattern we were talking about earlier for general chronically ill folks.

Nirala Jacobi:

I read a couple studies that showed the microbiome imbalances that go along with COVID and an increase in Campylobacter and Klebsiella, I think, and a decrease in butyrate producer. So, that's not really surprising. And then an increase in actual candida and aspergillus in the gut in one hospital setting study. So I'm not sure if that's due to ... surely they've also gave along antibiotics and a cocktail of things that you get when you're in the hospital.

All of this COVID pandemic has, I think, really shone a headlight on, or a spotlight on this issue of chronic viral illnesses. So we're starting to find out a lot of these associations that we didn't know existed in a way.

Paul Anderson:

Yeah. And the ability for people to do a lot of expensive research very quickly under the guise of COVID I think is making it possible for them to do a lot of this stuff too.

Nirala Jacobi:

So let's start moving into what can be done about this. Now, I want to just alert, I want to just have a little disclaimer here for people, when you're dealing with chronic illness, it's probably not a good idea to just willy-nilly start taking, or sort of patching together a treatment plan. Although, a lot of people are doing that, but I, most of the time, don't find that very helpful. So to really find a qualified practitioner that can help you unravel some of these health mysteries that you have, and to put you on a protocol, that's really going to work for you, just want to say that because a lot of people are taking tons of products that may not be appropriate for them.

But moving into treatment, how are you approaching that? And just to reiterate that clinical pearl that you gave at the very beginning of this podcast, where you talked about that in a way, a confirmatory of whether or not you have a viral illness that's affecting your gut is treating that viral illness and if your gut symptoms are getting worse. So, that I found just super fascinating.

Paul Anderson:

I think there's two patterns that I've seen with GI effect, and now that I'm ... believe I'm more aware of what's going on, it makes more sense. But one of them is which I think is a little bit more common because of the mechanics of what happens when you start to treat viral issues, is that you actually get some GI aggravation early on. Because if you envision the fact that the virus lives inside the GI cells, instead of living in the gut proper, and then we do things that make it hard for the virus to replicate or do its normal transactions, then what happens is the first step is to essentially bother the virus somehow.

Second step is that causes the immune system to notice those cells and essentially clean them up, to take them out and let your body regrow normal cells. The process of the immune system going after the virally infected cells involves inflammation. So I think that's why in many people we see a little aggravation early on, and then it starts to actually improve once you get past that.

So treatment wise, what I like to let patients visualize that we're trying to do is we want to support both sides of that equation. And let's take the most simple, maybe it wouldn't be the one that we would use a lot or all the time, but the most simple approach is actually an antiviral drug for cytomegalovirus or Epstein-Barr. What those drugs do is not like an antibiotic. All they do is they chemically stop the virus from being able to replicate, which is good, but the removal of the virus is the job of the immune system.

And so if we do not support the immune function and all we do is aggravate the virus, we get a little bit of a win, but then the virus will eventually start to work around that. So I always tell them we need both sides where we need to do something to directly make it very hard for the virus to persist. And there's a lot of botanical substances are very good for that. And then we normally also have them on something that's more of a broad immune support, so that as the immune system up regulates, it's being supported to do its job of cleaning up the mess that's left behind.

And that's one reason why even in gastroenterology, when they might give anti-Epstein–Barr, anti-cytomegalovirus drugs, sometimes it doesn't last very long or the effect doesn't work as well because the immune system is still running so slowly. It has no support to do the cleanup that it has to do. And it's well known in the pharmacology of those drugs, but the clinicians, the average allopathic clinician isn't thinking about supporting the immune system on the other side.

So I think that the immune support is as important as assaulting the virus and the virally infected cell. And you really need both. And then you get more of a complete response, but it is good to let people know ahead of time that if we're on the right track here, we may aggravate some of your symptoms. And so we need to stay in contact so we can deal with the aggravation, because usually there's things we can do palliatively to get you through that.

Nirala Jacobi:

Well, and the fact that 80, 90% of the immune function of the immune system is really in the digestive tract. Do you focus your immune support more on the GI immune response? So in the form of sort of bovine serum IG or ... I'm just thinking specifically support for secretory IgA for gut lining and in terms of zinc and vitamin A, and not to say that we need to spell out a whole protocol, but just in broad strokes, what do you prioritize in terms of your antivirals and immune support?

Paul Anderson:

Yeah, I think as you describe it, if the person has more of a body wide picture that involves some GI, it may be a mixture of more systemic immune support, et cetera. But if the complaints really are focused and localized to the GI tract, whether it's post-COVID GI issues or simply an aggravation of a chronic GI patient's case, if it's mostly GI oriented, then I would tend to look at using some direct antiviral herbs orally. So they're going to get to the gut.

And then the things you mentioned, supporting the microbiome, number one, through dietary and appropriate, maybe probiotic things, but supporting, as you mentioned, the secretory IgA. So IgA being the protein that ... the immune protein that is largely protecting the gut lining, et cetera. And those things you brought up a colostrum or transfer factor based type products, I find those very well tolerated for most people and for these GI purposes, probably some of the best things to do. And then there are other really good adjuncts for that GI immunity beyond prebiotic and dietary things and maybe a transfer factor colostrum such as vitamin A and zinc and some trace minerals.

In people who can tolerate them in their picture, mushrooms, mushroom extracts, medicinal mushrooms can be very, very useful as well, because they kind of hit both sides of that equation where they're a bit directing the immune activity against the virus and supporting the immune function together. But like you said, especially with gut things like this, you really want to have a practitioner to kind of orchestrate this for you because you can stir up more than you were planning on if you go too fast.

Nirala Jacobi:

Absolutely. And in my practice, I do a lot of genomic testing as well. And a number of people, or I'd say a lot of people with chronic gut issues also have genomic profiles that kind of entrench them in this chronic gut picture. And then additionally, if they have a virus, this can really complicate matters and you need a really personalized treatment plan.

For example, the FUT2 gene that when people are secretors or non-secretors and using ... Or I was reading something about these fucosylated polysaccharides and how viruses can actually attach much easier when somebody has this genomic issue or variants in their picture. So, that means that their bifidobacterium will be low. Their mucosal regeneration will be impaired. Their B12 absorption will be impaired. And all of that factors in when we're dealing with these chronic infections, I think, also.

Paul Anderson:

Oh, certainly. Yeah. In my opinion, the ability to look at a lot of the genomic and nutrigenomic profiles has really, at least, given explanation to people who may be slower to heal or much more sensitive, or maybe that you need to go a little more gentle with just because of their genomics and their ability to process things. So, I think all of that really makes a huge difference.

Nirala Jacobi:

I want to wrap up because ... and we've had a lot of technical difficulties. I want to say this, if people have noticed that there's been some sort of sound change in the middle, we're used to problem solving. So we've solved that problem. We moved on to another platform. So we're able to complete this podcast. But I want to give you an opportunity just to mention, first of all, also this podcast that you talked about, where I think it's your podcast, where you talk about COVID and other viral infections. And also where people can find you, your different platforms, before we wrap up, so that there's plenty of time in that. And people that are listening, you can also find this in the show notes.

Paul Anderson:

Certainly. So the specific podcast I was talking about is, I do a weekly podcast about medicine and health. That's the name of it. And there's one we just recorded yesterday, which will be up on YouTube very shortly, specifically was about newer research around post COVID, et cetera. And as I was mentioning, it was just sort of a happy circumstance that there was this new information about gastrointestinal effects of COVID in post COVID. So, that'll be up. The podcast lives long term, either on any pod burner.

If you look up Medicine and Health with Dr. Paul Anderson, or the video version is on YouTube. And my YouTube channel is just D-R-A, doctor A online. And if you search that now on YouTube, generally you find me, you'll see a picture of me. And the latest one, it'll be probably the July 1st, 2022, is that specific one. That one, in those show notes, we'll also have links to those research papers and things, kind of a little more detailed links. And if people can't find me on any of those ways, I have a hub website that has links to all these things. And it's very simple. It's just D-R-A-N-O-W, DrAnow.com. And it's got links to all my media, because I've been told I do too much, too many media outlets.

Nirala Jacobi:

You're spread too thin. You're all over the place.

Paul Anderson:

I'm doing too many things.

Nirala Jacobi:

And practitioners, please also check out your ... is it a yearly conference or you do twice a year, the AAMP?

Paul Anderson:

Yeah. We do it twice a year, a spring and a fall. And it's Advanced Applications in Medical Practice or AAMP. It's an M and not an N. And if you just go to AAMPconferences.com, you'll see our lineup. And we focus on the chronic illness space specifically, because it's so complex and there's so many new things. And so we experts in who are topical. So every few years we generally have say, a GI focus. And then we may have more of an endocrine one coming up, hormones. And we do a cancer one every two years. So we kind of rotate through things. We just did a neuro focused one, but that's practitioner oriented, but we do two a year for the last five years.

Nirala Jacobi:

Oh, great. And what's the one coming up in fall?

Paul Anderson:

It's endocrine.

Nirala Jacobi:

All right. Cool. I'll have to check that out. Well, Dr. Anderson, it's been a pleasure. We got there, we got to the end. We patched it together.

Paul Anderson:

It was fun. It was fun, no matter what.

Nirala Jacobi:

No matter what. It's always a pleasure to talk to you and to get your insights into these complex conditions that we're seeing in practice. So, thank you so much for your time.

Paul Anderson:

Well, thank you for having me. It's always fun.

Speaker 3:

Thank you for listening to SIBO Doctor podcast. We hope you find the information in this episode useful in the treatment of your SIBO patients. Thanks to our sponsors, SIBOtest.com a breath testing service with easy online ordering. Thanks again for listening.