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Immune Resilience: How the Microbiome Affects Immunity with Romilly Hodges

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Immune Resilience: How the Microbiome Affects Immunity with Romilly Hodges

with Dr. Kara Fitzgerald

With an ongoing pandemic that doesn’t abate, is it any wonder immune health is on everyone’s mind? As we adapt to these unprecedented times, the interest in supporting immunity has skyrocketed. So, I couldn’t wait to interview my dear friend and long-term colleague, Romilly Hodges. With her new book Immune Resilience just published, I’m thrilled to share Romilly’s exciting pearls on immune health on New Frontiers. You may know Rom from her time as Nutrition Programs Director at our clinic and her work on our Methylation Diet & Lifestyle program. Romilly is all that, and so much more: also a CNS, IFMCP, and vastly published author in several peer-reviewed journals.

In this very special episode, we discuss the role of the microbiome in infection defense and immune system training, the effects of nature exposure, the ongoing pandemic and immune system development, immune tolerance and micro-exposures, and how sleep affects vaccine efficacy. It’s a lot! Romilly also reveals strategic multifactorial interventions and the power of whole foods over supplements. This research-packed discussion will leave you wanting more – to be continued for sure! As always, thank you for listening and please do leave a comment wherever you hear my voice. – DrKF

Immune Resilience: How the Microbiome Affects Immunity with Romilly Hodges

Ever wondered exactly how the gut and immune system interact? And how does the digestive tract protect us from infections? In this episode of New Frontiers, we’re diving into the world of immune resilience with Romilly Hodges, MS CNS CDN IFMCP. Romilly is a certified clinical nutritionist and functional medicine practitioner, the author of several peer-reviewed journal articles as well as her recently published book Immune Resilience. She also played an integral part in developing the Methylation Diet and Lifestyle program during her time as Nutrition Programs Director at our clinic. In this podcast, Romilly shares valuable pearls from her book journey, including the benefits of micro-exposures and drawbacks of elimination diets, the mechanisms by which the gut protects us from pathogens, nature’s role in immune development, key nutrients and dietary patterns for immune health and a ton of interesting research on the gut-immune axis.

In this episode of New Frontiers, learn about:

  • Micro-exposures
  • Elimination diet drawbacks
  • Oral immunotherapy
  • Cross-reactions
  • Gut defenses against infections
  • Active tolerance
  • Natural environments
  • Covid & immune system development
  • Strategic multifactorial interventions
  • Vitamin D & microbial diversity
  • Dietary patterns & immune health
  • Stress, sleep & toxins
The Full Transcript

Dr. Kara Fitzgerald: Hey everybody, welcome to a New Frontiers in Functional Medicine, where we are interviewing the very best minds in functional medicine and today is no exception. I am thrilled to be with my dear colleague and friend, Romilly Hodges. Let me give you a little bit of her background, you’re likely familiar with Romilly, but let me give you her backstory, and then we’re going to jump into our conversation about her new book which I’m so excited to be sharing with you. Romilly is a clinical nutritionist certified by the American Nutrition Association in the State of Connecticut. She’s also a certified functional medicine practitioner through the Institute for Functional Medicine. She spent several years as the founding director of nutrition programs at our clinic and we are a teaching clinic in Connecticut in the USA and as well as being a clinician, Romilly has written for several peer-reviewed journals, textbook contributions, professional training programs, online articles, and has been a speaker at several conferences.

Most recently, she authored the book Immune Resilience, and it’s published here in the U.S. and internationally and it’s available now wherever books are sold. She has primary research experience, having designed the first of its kind epigenetics study diet for a clinical trial run through National University of Natural Medicine in Portland, and now published in the journal Aging that demonstrated the possibility of biological age reversal using diet and lifestyle. Of course you know that as our Methylation Diet and Lifestyle program, now rebranded as the Younger You program. Romilly has developed successful educational programs for nutritionists and functional medicine practitioners, and she serves on the board of accreditation. She serves on the board for the Accreditation Council of Nutrition Professional Education, a subsidiary organization of American Nutritional Association. Rom’s been featured in publications including mindbodygreen, Experience Life Magazine, Wall Street Journal. You can find more about her and her book at romillyhodges.com or immuneresilienceplan.com.

Romilly, welcome, welcome, welcome, to New Frontiers.

Romilly Hodges: Oh my goodness. I am just so excited to be here and I’m totally and utterly humbled to be here honestly given all the work that we’ve done together over the last several years. It’s just been the most amazing journey, and I feel like this is the culmination point honestly, being on New Frontiers in Functional Medicine is just such a highlight and I really appreciate it and I’m looking forward to this discussion.

Dr. Kara Fitzgerald: Yay, it’s just fabulous to have you on this side of the … On the other side of the microphone. It’s really cool.

Romilly Hodges: Although I have to say that one day we should be interviewing you on this podcast. Because you’ve got … We need to mine the Dr. Fitzgerald brain at the same time as everybody else’s, but … For another time.

Dr. Kara Fitzgerald: Hey, I’ll turn that mic over to you whenever you want it. But listen, you have been thinking about immune health through the nutrition lens for a long time actually, a long time. This has been so fundamental to your work here in the clinic and even before that. Can you talk to me about why?

Romilly Hodges: Yeah, yeah. So well, immune health is really what got me into this field in the first place because I actually had a previous career, I was working as a research analyst in a business and technology think tank in New York City and that’s pretty much as far away from nutrition as you could get. And then I became a mom, and you know, you have kids, stuff happens, and one of my kids had a bunch of different health challenges, and everything changed, everything changed, and you know as a mom, you just want to do whatever you can to help support your kids.

And so I started researching. I sort of redirected that research brain and I was putting it into the direction of trying to figure this out, and one thing led to another. These are the doors that opened and the more that it worked, the further we went and one thing led to another. I mean for him, my son, he had a whole bunch of digestive issues when he was an infant and eczema that came out top to toe and then food allergies diagnosed and so that was really the turning point was all of these immune challenges that he was facing, and trying to figure those out and not least of which was eventually, the instruction was sort of avoidance of trigger foods and medications to suppress symptoms and things like that and I had all these other questions about, “Well how do I keep him nutritionally replete? How do I try to dial down what’s going on with his immune system?” I learned about atopic march and how could we prevent progression of immune symptoms and conditions from developing, all of those questions.

So that’s really what led me into the field of immune health and luckily enough to working with you because that’s always been a huge component of your background as well, even as you’ve had many other areas going on at the same time, but … So it’s just been the central driver really to what I’ve done and where I’ve sort of ended up in this field so far.

Dr. Kara Fitzgerald: It’s extraordinary. It’s the power of a focused mom, and then without adequate questions, and then your research brain, your ability to ask questions, your ability to tease out what’s happening deeper and deeper and deeper and then create practical application of your findings. So translating the science into clinical application, into at-home application with your extraordinary work with your son. It’s just an amazing journey Rom. It’s just an amazing journey and one that I just have such a high regard for, thinking about his allergies and just the moments as a mom, you and I talk mom to mom. He’s older than Iz and what to do when your son goes into anaphylaxis, just moving through this and feeling that as a mom, but then being … And concurrently, turning that around and figuring it out, and using the best science really the world over. I mean you’ve done such good work in this arena, not just in your family thank God, you’re sharing this and I just want to so recommend Romilly’s book for just this breadth of experience and the mind that she brings to it.

And so you and I were always. So to this point, and I teach on the immune module at the Institute for Functional Medicine for anybody who doesn’t know, and so Rom and I have absolutely shared this passion and this desire to dive deep and translate the science into clinical applicability and see what we’re seeing. So as we see the incidence of allergy, atopic disease, et cetera, et cetera, we see the rise really quickly and needing new tools, better tools and more refined tools. We’ve done a lot of, I think, pretty innovative work here, and do you want to talk about some of the pieces that really stand out to you?

Romilly Hodges: Yeah, oh for sure, for sure, and I really credit these two, kind of your thinking and being in the clinic with you and how we evolved. Not just what maybe I had experienced personally at home, but like what we were really seeing in clinic as well.

Dr. Kara Fitzgerald: Yes.

Romilly Hodges: So I think there are a couple of things that I think are worth mentioning because they’re not always the first things we think about when we’re talking about immune health and how do we protect the immune system and keep it balanced and healthy. And one of them is micro-exposures, so maybe we can talk a little bit about that first and one of the … So there were these key studies that came out, the LEAP studies, that looked at micro-dosing or at least early exposures to potentially antigenic foods in infants and that led to changes in what pediatricians are recommending to be able to introduce these food allergens earlier in a safe way to kids that were at higher risk of developing food allergies. Obviously not to kids who already had food allergies, this was preventative. And so that was one instance of sort of micro-exposures that led us to say in our patient population, look at things like this product called SpoonfulONE which is designed to have small components of the top antigenic foods in it that can be used in infants to provide that early introduction to potentially antigenic foods and reduce the risk for development of food allergies and such.

But then we took that as well and combined it with not only some of the things that we were seeing in clinic, which were that some patients … So elimination diets, right? Very cornerstone tool of functional medicine, but you remove antigenic foods or potentially antigenic foods for a period of time and then reintroduce them. In certain individuals, we would see that actually going through that process, eliminating a food and then reintroducing it, would provoke sometimes a higher level of reactivity, and we never experienced sort of an anaphylaxis version of that where there hadn’t been before and obviously we wouldn’t be challenging that in a known allergy but there are also some papers that have been written that have observed this phenomenon as well.

So for instance, there was a paper published in 2016 from the Chicago Northwestern University Feinberg School of Medicine and they quantified in their population that they looked at that 19% of patients that had food triggered atopic dermatitis but no previous history of any immediate reaction did develop new immediate food reactions after initiating an elimination diet of that food, and in 70% of the cases, those were cutaneous, so skin-related, but 30% were also anaphylaxis, and they noted that cow’s milk and egg were the most common there.

And there are a few other papers that also have observed this as well. So back to the micro-exposures, what we started doing was using micro-exposures during an elimination diet in individuals who we thought were at higher risk, so perhaps history of allergic disease or symptoms that suggested that and during the elimination diet using something like SpoonfulONE at a very low level to avoid a total elimination of that, it was just really like bringing it way, way, way down, but avoiding a total elimination in certain individuals. But I’d love you to add your comments as well because your thinking was really key in how we did this, so …

Dr. Kara Fitzgerald: I want to say one thing which is I didn’t see this phenomenon early in my career. I think that it’s on the rise, this loss of tolerance, and it’s just part of the whole rise in allergic disease. Like I didn’t see eosinophilic esophagitis, I mean it wasn’t characterized until … When was it first characterized? Like the mid 2000s. I mean –

Romilly Hodges: It was definitely after 2000.

Dr. Kara Fitzgerald: Yeah, yeah, I mean so we’re just seeing this meteoric rise in allergic disease but also autoimmunity. I mean you can kind of look at it across the board. And so we wanted to reduce the burden of exposure, so there’s still … Even with a reaction, there’s still some thread of tolerance, like it’s not all the way to anaphylaxis, or there’s still some thread of tolerance there, and so giving them just a micro amount could expose the immune system to this compound so that whatever shred of tolerance is there is maintained and it doesn’t dip into a worse reactivity or a new reactivity, et cetera.

Concurrently though, I think it’s important to point out in a functional medicine practice, we’re working on building tolerance along with the elimination diet, we’re doing lots of work. It’s not an elimination diet in a vacuum. And then the other thought that I had was that we know from the literature that if you reduce the quantity of exposure, I mean that’s commensurate with reducing the potential for reactivity or dropping some of the immune complex that’s in circulation. So minute exposure can be a successful component of an elimination diet is what I’m saying. Does that all make sense?

Romilly Hodges: Yeah, yeah, it does, and would you add anything to who we are thinking about this in?

Dr. Kara Fitzgerald: So it’s funny, I was just lecturing at the immune module and just all of this is fresh in my mind. So definitely those with atopic disease, I think that’s been very well-documented, and it’s certainly been our experience here. Definitely in infants, I think across the board unless as you said there’s already an established allergy, we want to be introducing food way earlier than previous and not just peanuts but really some micro-exposure to all the antigenic foods so they’re able to develop some tolerance. We have some anecdotal case reports from practice now that this is really successful and it’s very gratifying to see this.

I am concerned about loss of tolerance and other hypersensitivity reactions to food, so yeah, I am Romilly, meaning to using some kind of a micro-exposure structure more broadly. Yeah, so –

Romilly Hodges: And we certainly do have experience of obviously increased rates of allergies, there are instances where children are getting allergic disease or like anaphylaxis allergic disease when their parents didn’t have that before. So we are seeing this trend. So I also think that it’s prudent to be considering this fairly broadly, yeah. And I also think of it similarly to OIT, which I also went through, we also went through with my son. But the concept of OIT, which is oral immunotherapy for certain individuals who are eligible who have food allergies. What you’re really doing is that continual small dose exposure actually suppresses immune response to a certain level, so it’s a similar kind of concept with these micro-exposures and you don’t want to necessarily remove all exposures because you can leave it vulnerable to increasing. And should I mention the other one?

Dr. Kara Fitzgerald: Let me –

Romilly Hodges: Yeah, go ahead.

Dr. Kara Fitzgerald: Yeah, go ahead Rom, go ahead. Well actually, I was going to say, so just thinking more broadly in other elimination diets that might not be immune mediated like small intestinal bacterial overgrowth and putting somebody on a FODMAP, we’re really rethinking that as well. So these are non-immunological reactivities but we see people on long-term FODMAPs or long-term low histamine, et cetera, et cetera, with micronutrient deficiencies and inability to reintroduce foods. I mean we just, we see a lot of fallout with highly limited diets and I would see a trend that’s happening in our clinic and elsewhere is damage to the microbiome when there’s such a limited amount of foods being exposed. So an important trend is allowing as broad a diet as possible.

Romilly Hodges: Yeah, yep. I would fully concur with that. I mean I think we always have to look at what we’re doing and see how it needs to be evolved because it just always does. I mean it’s not just elimination diet and done or low FODMAP diet and done. We have to be thinking of that long-term what does that mean for all of the different knock-on effects and what is the appropriate thing for somebody in six months from now, one year from now. Because the immune system changes, your microbiome changes. Your need for all of these different therapeutic diets is not necessarily endless, and it usually isn’t, so we have to be thinking about that.

Dr. Kara Fitzgerald: And we don’t want it to be. We don’t want it to be. Yeah. Go ahead.

Romilly Hodges: Yeah. Well so the other area that I think we’ve been doing quite a bit in is cross-reactions, and looking at the concept of … So cross-reactions involves sensitization to an original allergen, usually a pollen or something environmental, and then the cross-reaction is with different foods that share very similar kinds of proteins, and so the body would see them and react to them in a similar kind of way. Not necessarily all of the time, it’s somewhat selective and sometimes not at all, and so for instance, somebody who’s sensitized to birch pollen might react to something like apple or carrot or celery or may not, but these are potential food cross-reactions and usually that manifests as an oral allergy syndrome, where the symptoms are just localized to the mouth, but I think what’s different about what I’ve seen in clinics and me working with you and learning from that is that sometimes we can see more systemic manifestations even from these cross-reactions, such as skin conditions or headache, pain, joint pain or even IBS types of pain as well. So that has been an expansion of the thinking I think around how we look at cross-reactions. There was a –

Dr. Kara Fitzgerald: Go ahead.

Romilly Hodges: Go ahead.

Dr. Kara Fitzgerald: Well I was just going to add EOE into that mix, eosinophilic esophagitis or any sort of gastroenteritis is sort of … For my, kind of the classic oral allergy syndrome moving a little bit more deeply. But yeah, go ahead with what you were going to say.

Romilly Hodges: No, well I was just thinking of a really interesting case that we did have in the clinic where there was a shrimp, crustacean sensitization, so a known reaction to shrimps, but then this sort of puzzling picture of nighttime hives when there was not a shrimp in sight and things like that and one of those cross-reactions with shrimp and other crustaceans is actually dust mites and in this instance it turned out to be the reactions to dust mites as a cross-reaction to the shrimp antigens. So that was really an interesting aha that that cross-reactivity can really take on such an extensive symptom picture.

The other one that I want to mention as well, because we’re seeing a lot of health foods that contain things … Ingredients like crickets or other insects, and what isn’t widely communicated as well is that actually crickets and insects can cross-react with crustaceans, so individuals who have seafood allergies may have cross-reactions with these different other new types of foods that we’re seeing, so yeah, I think it’s an important one to just have on the radar.

Dr. Kara Fitzgerald: Yeah, and two interesting things about that dust mite case, that patient where he had a severe dust mite allergy. It was not your garden variety wake up with a sneeze, the most common presentation. It was significant as you expressed with his nighttime hives and his inability to get a full night’s sleep. And so we did good work with him with a full dust mite elimination. Like he cleaned that house within an inch of its life. I mean it was really extraordinary, except for his daughter’s room. They had massive air purifiers; they just did everything to the nines because he was experiencing some symptom relief. But fascinating to me Rom and just circling back to this micro-exposure phenomena is that he said that when he went … After doing this elimination that he noticed he was more reactive when he went into his daughter’s room, where there were some remaining dust mites. It was the one room in their home that hadn’t been cleaned to within an inch of its life, and his reactivity had actually increased a little bit within that environment. It’s just an extraordinary thinking that we’ve got to be careful in scrubbing everything away, that some micro-exposure to dust mite may be in order.

Romilly Hodges: Right, right. Even as you’re working on all of those underlying immune building factors or immune balancing factors that are working on restoring that sort of tolerance at a broad level.

Dr. Kara Fitzgerald: 100%, that’s exactly right. In my mind the only chance we’ve got, yes we can do these therapeutic diets and so forth and clean up the environment in the case of the dust mite allergy. But if we are not doing all of the underlying foundational, functional work, really I think our efforts are going to be for naught.

So you’ve written this amazing book that I know has already received high praise from key people in our world. I know Bob Rountree was working with you as a reviewer.

Romilly Hodges: He was great. Yeah.

Dr. Kara Fitzgerald: He sung your praises to me in the work that you’ve done. Let’s talk about some of the interesting things that you’ve learned during the book journey, during this dive into the book. Things that have shaped you and will influence how you practice and no doubt us as well others.

Romilly Hodges: Well, it means a lot that you say that and he says that honestly, but I think … Some of the, if I really tried to distill it down, there are some themes I think that are the most interesting learnings along the way, and really those come down to we have to do that foundational work, so we’ve just been talking a little bit about that in the context of all kinds of crazy stuff that might be going on. We have to be working on the foundations. And we have to be thinking broadly. It’s no good just taking a very narrow view and focusing all our interventions on one slice of the pie when there are a whole host of different things that can affect immune function and for one person they might be one thing, for another person they’re another thing, and so we have to take this perspective which is what functional medicine is so good at doing. It gives you that structure, that broad lens to look at all of these different things.

But I guess I’ll mention a couple of things. So this book is really focused on … Or primarily focused on immune health against infectious diseases. Partly because of the context of the world that we’ve been living in for the last two years in this pandemic, but that’s the lens. So if I mention barriers for instance, we’ll be thinking for allergic disease or for autoimmunity, we’re always thinking about build back your barriers, the gut barrier, everything has to be working well to prevent that kind of immune dysfunction, but we also need our barriers critically for immune health against pathogens as well. Everything, from how much saliva we’re producing to do we have enough stomach acid. I mean there are some really interesting JAMA papers on acid suppressants being linked to having multi-drug resistant germs living in your digestive tract and episodes of recurrent C. difficile. Even pneumonia and these are all published in really respected journals and acid suppressants for reflux, we’re not suggesting immediately go ahead and stop your medication but of course in functional medicine there are different ways to approach conditions like reflux. So we can be thinking about those.

Bile, bile is also very naturally antimicrobial. Secretory IgA, that’s another big one. We measure it easily in functional medicine. It’s the most abundant antibody type in our mucosal immune system and it’s got all these different roles in working to keep us safe against pathogens. And it’s also involved in tolerance as well, so it has that aspect to it too. And mucus. So we love to talk about poop, so I’m sure we won’t mind talking about mucus, all right? I mean mucus, we don’t talk about it that much in functional medicine, but it’s really essential for our immune system to work properly. Like we actually have these two different layers of mucus. We have an inner layer and we have this outer layer, and in our small intestine … So the inner layer, it doesn’t have our … There’s no bacteria in that inner layer. The bacteria are kind of in the outer layer of mucus. And so we have these two distinct zones in our mucus layers, and in the small intestine, the tips of the villi reach into the outer layers, where the bacteria are, where our microbiome is, where everything else is, but most of the villi is actually in the inner layer.

In the colon, our lining of the colon is totally covered by the inner layer and the outer layer is totally separate, and this is important for a few different reasons. Not least because when that mucus barrier degrades, you get bacteria and other things more in direct contact with the surface of the digestive tract and that creates all kinds of dysfunction. Our immune system likes to have things stand back at a little bit of a distance so it can kind of get a good look at it, it can sample things in a sort of orderly fashion, and when it’s not there, everything gets into disarray and you get inflammation and more inappropriate types of immune reactions happening as well. So it’s not just about tight junctions in the digestive tract. We have to be thinking about other things like this mucus layer as well.

Dr. Kara Fitzgerald: That’s great. That’s such a good pearl. Well can you just throw out a thought on how we nourish that or when we start, we’re going to talk about nutrients and so forth, do you want to bring it in at that time, because everybody’s going to want to … Yeah.

Romilly Hodges: Right. So no, let’s mention it now. I think it would be a good idea. So for our mucus layer, it’s really a lot about fiber because when we eat fiber, through the interactions with the gut microbiome, we produce more mucus. So there was a study in Cell Journal in 2016 and it was an animal study but they transplanted human microbes into the digestive tract of these mice and then they fed them either a high fiber or a low fiber diet and what they saw with the high fiber diet was this healthy layer of mucus in the digestive tract, but with the low fiber diet, they saw that degraded and then when they introduced a pathogen, they saw heightened susceptibility to that pathogen and increased levels of inflammation. So fiber is a really big thing for your mucus layer and Vitamin A. Vitamin A is really essential for your mucus because it’s needed for the production of it, for the different glycoproteins that are in there.

Incidentally, these glycoproteins in mucus are also pretty interesting in that they help feed your microbiome in between your meals, which would otherwise feed your microbiome. So it’s an interesting, we tend to think of this like period … It is, it’s like this period in between your meals, it’s good for kind of culling excess microbes in your digestive tract, but they’re not totally at a loss because they do have this mucus layer that is rich in glycoproteins which can sustain them. So I quite like that as well.

Dr. Kara Fitzgerald: Gosh, it’s very interesting and it just makes me think that there’s probably some … There’s a rebuilding and regenerative process going on and this is an essential way that we’ve evolved and it makes me also tack onto that doing a little bit of time restricted eating so we’re very intentionally giving room for our microbes to kind of clean up the mucus layer, to recycle it, turn it over, allow new to come in. It’s just extremely fascinating. I know we could probably talk about this forever and gosh Romilly, I could see you sort of growing out this thinking. So important, really. I’m glad that you’ve brought this to us today and I’ll look forward to more conversations here.

Romilly Hodges: Yeah, the other thing, if I could jump into maybe another thing that I think is really interesting is really … And again, it’s going to sound like I’m talking about something that we all have spent a lot of time talking about and that’s your microbiome. But I think we need to continue to just really understand what is going on here with our microbiome and just how relevant it is to immunity and again not just for allergy and autoimmunity, but protecting you against infectious disease as well and so much so that I think even in the book I’m referring to it as this kind of like environmental immunity, they really are like totally strategic allies in our defense system against germs. So they’re first of all crowding out, competing with pathogens for space, so when you nourish the good guys, there’s just less room and less nutrition for the bad guys to be there. We all know about short chain fatty acids, of course they’re very nourishing to the gut barrier, they improve tight junctions, they have all these epigenetic effects, they’re anti-inflammatory, they balance our immune system through T Reg cells and things like that.

And then also, short chain fatty acids are known to reduce the virulence of certain pathogenic bacteria as well, and our microbes produce these compounds called bacteriocins which are basically anti-microbial compounds that they produce that act against pathogenic bacteria. So they do all sorts of things that our immune system also does, but they degrade membranes or they poke holes in the membranes of pathogenic microbes or they interfere with their replication and there are examples. Interestingly it’s often a species within the same group that are working against pathogenic varieties of the same type of –

Dr. Kara Fitzgerald: That’s fascinating

Romilly Hodges: It is. Exactly.

Dr. Kara Fitzgerald: So like commensal clostridia. Yeah, go ahead.

Romilly Hodges: Yes, exactly. And then E. coli, right? So we have beneficial E. coli, like E. coli Nissle, and that works against pathogenic E. coli. Or on your skin, Staphylococcus epidermis works against Staphylococcus aureus through these bacteriocins. So it’s really fascinating.

They also introduce what I call tone in your immune system because when you have microbes there, even the good kinds, your immune system always is on alert. Like it’s totally … It’s stimulated into the processes of sampling what’s out there through dendritic cells or producing secretory IgA. So it’s constantly keeping your immune system at a toned level and alert to what’s going on.

Dr. Kara Fitzgerald: It’s like active tolerance is how I think of it.

Romilly Hodges: Active tolerance.

Dr. Kara Fitzgerald: Tolerance isn’t you just saw it and forgot it. Okay, we’ve established the memory that this is okay, it’s not that way at all. It is as you say, it’s tone, that’s an awesome adjective or … Yeah, or active tolerance.

Romilly Hodges: Yeah, yes. It just keeps your immune system on its toes basically in a healthy way, and then last but not least, it’s really involved in training your immune system with how to behave, and we know there is lots of research out there on how dysbiosis is associated with allergies and autoimmunity and infectious diseases as well. And we know there’s germ-free mice studies where you can see that these mice end up with smaller sinus glands and spleen, they have less active T cells, natural killer cells, their B cells become skewed towards IgE production, they have a reduced number of T cells, et cetera, et cetera. And so we have this picture about sort of training the immune system through our microbiome and there’s really also another study that I find totally fascinating, a longstanding study or data collection and analysis which has produced several research papers over the decades and that’s … It was done in the Karelia region which is a region that spans across Finland and Russia and after the Second World War, there was a large part of the land that was ceded from Finland to Russia in that region and then it was kind of closed off and there were no visitors for the next 50 years or so.

And so the two sides of that region developed very differently. On the Finnish side, there was more modernization, and on the Russian side, there was this sort of adherence to traditional farming methods and working the land, being out in nature a lot more. And so by the early 2000s, it became very clear that allergic disease on the Finnish side was really taking off and there was next to none on the Russian side, so some of the quantification of that is in the early 2000s, 2% of schoolchildren on the Russian side had sensitization to birch pollen compared to 27% on the Finnish side. And then they followed these individuals and so as adults now, they report 3 to 10 times more allergic conditions in the Finnish side compared to the Russian.

And the researchers are teasing out this thread of the microbiome and they’ve reported that the skin and nasal microbiota is much more diverse on the Russian side and then that seems to be linked with lower allergy prevalence and more varied antibodies in general. So again, it’s just this really interesting view and reporting of just important the microbiota is for our immune health.

Dr. Kara Fitzgerald: They have well an interaction with the greater, the greater microbiome. So they have more forest, more traditional farming. They’re more one with earth, wouldn’t you say?

Romilly Hodges: Yep. It’s that good kind of dirt. Basically all things that are connected to the hygiene hypothesis, just manifesting in lower rates of allergic disease. I mean it’s really interesting, I have a whole section in the book on just our interaction with natural environments and some of the research that’s there. I think it’s very important.

Dr. Kara Fitzgerald: Yes. I want to just say one more thing about this region because I thought about it for the immune module as well. So the Russian side has more … Shares bacteria on their skin with plants. So they’ve got this connection, this literally direct connection in their diverse microbiome and it’s reflective of the environment that they live in. I just think that’s super cool.

Romilly Hodges: That is, that is. But you know, it also makes me think … And I’d love to hear your thoughts on this as well because what that really tells us most conclusively I think is that diversity is really important in the microbiome. Yes we have some data that’s emerging around like specific species help with this, but overall the most compelling conclusions that we can draw is that diversity is really important. And so how do we support diversity in our microbiota? It makes me think that we don’t necessarily do it with a probiotic supplement that contains just a couple of strains. And I’m not saying that they don’t have a place, we definitely use them and they’re very useful. But if we really want to establish diversity, I think we need to be thinking about really emphasizing those prebiotics so that those fibers and the polyphenols in the plant compounds which are also prebiotics as well and fermented foods that have a much broader range of probiotic species in them than we can get in a supplement and often also in greater quantities as well. So yeah, I’d love to know your thoughts about that too.

Dr. Kara Fitzgerald: Yes, 100%, and again, getting outside and into nature. So one more thing, because we’ve got so much to cover here, but you know we’ve been tossing around the idea that during COVID, is there a halt in immune system development since … In early COVID, when kids were out of school and so forth and I was thinking about my daughter who was just in preschool and not going through the litany of infections that she would have otherwise, her immune system was really sort of put in this halt, this kind of suspended in animation place and was this healthy? We dialogued about it here during our rounds and we’ve got of course an amazing pediatrician, Lizzie Bird, who weighed in a lot, and her position was, “I don’t think that kids benefit from that litany of viral infections,” and of course some of those, once we’re exposed they’re lasting and we know cytomegalovirus, Epstein-Barr and RSV even can have problems, fallout years later. But she said kids need to be out in the dirt, they need to be in nature and so forth and Isabella is, but it was interesting to have that conversation and think about what’s right and certainly as time goes on, we’ll have more data points from COVID and toddlers, kids in active immune development periods. Do you have any thoughts on that?

Romilly Hodges: Yeah. I mean overarchingly, I think we will learn more as time goes on because this is just a totally unprecedented situation for the development of young people’s microbiota. So yeah, that we will see. I think yes, COVID didn’t remove our access to dirt for the most part and natural environments and I think that they are just incredibly important. Yeah, I think that the jury is out on how the missed opportunity or that period of time where there was that missed opportunity for exposure to common viruses and bacteria that go around and building immunity to those. We’ll see how that evolves. I think we can’t know that yet, but I certainly think that … It makes me think of building the microbiome in these kids as much as possible. Because we are surrounding them with antimicrobials at every turn really, and we have been keeping everybody sort of separated. That’s starting to change now of course, but yeah. I think it’s important to try to counter that as much as possible with these resilience building mechanisms like the microbiota, like good nutrition and preparing the immune system as best we can.

Dr. Kara Fitzgerald: So let’s talk about interventions. I mean everybody’s going to want to know how to build a good, healthy mucus bilayer of course and you’ve already addressed that with fiber. I’m curious if you have any favorites and then you’re talking about prebiotics and fermented foods, et cetera. But it’s easy in our world, in the world of functional medicine, you’re casting this really wide net so you’re dealing with the issue at hand but you’re looking at it through like this systems lens. We can have intervention overwhelm and this is probably one of the bigger complaints patients have when they work with a functional medicine provider that they’re overwhelmed –

Romilly Hodges: Holistic list of supplements, right.

Dr. Kara Fitzgerald: Yes, yes, yes. But I know you know how to think through one supplement being multifactorial, and not needing a supplement for every issue that you’ve identified. So what do you think? Strategic use interventions.

Romilly Hodges: Definitely. Definitely. Okay, so yeah. In fact, because one of the things I’ve always wanted to do is try to kind of put together these resources to show just how much we do with any of these one interventions. So for instance, if we take something like Vitamin D, of course we think about Vitamin D for bone health, we think about Vitamin D for T Reg cells, but it does even more than that. So it regulates zonulin, so it has a role in tight junctions. So when you take Vitamin D, you’re also supporting barrier integrity as well. And Vitamin D is actually a nutrient that’s totally critical for regulating our production of our own antimicrobial peptides. So it’s a little bit like the bacteriocins that I was talking about that some of these beneficial bacteria species produce. We also, on all of our surface layers, produce antimicrobial peptides and they’re totally regulated by Vitamin D and they’re absolutely critical to protecting those barriers as well. And Vitamin D is also associated, when you take Vitamin D, it’s associated with increased microbial diversity in the gut, so it’s an intervention for our microbiota as well.

So just thinking about these single interventions with all of their different multiple effects. Others would include say phytonutrients. Most phytonutrients are antimicrobial in their own right. They’re also prebiotics and they’re antioxidants and they’re anti-inflammatory and they’re epigenetic modifiers. So they’re anti-aging in that way as well as a whole bunch of other things. So they’re so pleiotropic in their possibilities.

So you’re taking something like quercetin for instance. We like quercetin a lot because it’s good for allergies, so it’s always on my radar. But it also is known to improve barrier integrity, it’s of course antioxidant and anti-inflammatory, it’s anti-allergy as I mentioned. And then it’s also antiviral and it’s sort of broad spectrum anti-microbial, anti-bacterial as well. And in fact, so there was human study that I looked at in the process of writing this book, which they used 1,000 milligrams per day of quercetin for 12 weeks and they showed that that reduced the number of sick days, this is a human study, due to respiratory tract infections, and they decreased the severity scores, especially in those aged over 40. So it’s got all these different roles that we can harness at the same time.

Dr. Kara Fitzgerald: That’s great. I want to just give a little extra love to Vitamin D. I am a massive fan of all the polyphenols including quercetin, I wrote about them. We have an amazing nutrient appendix in the book Younger You, which is a love fest to all of these. But really, if we had to isolate a single nutrient for its ability to influence the epigenome, I think it would have to be Vitamin D. I mean it gets top billing for so many things, but my read on the literature just in regard to Vitamin D and the number of epigenetic marks that it’s able to influence from DNA methylation to histone acetylation and methylation and mitochondrial methylation and on and on and on. All of those biochemical players influencing gene expression, Vitamin D, is right in there directing traffic.

Romilly Hodges: Very fantastic. It’s so interesting.

Dr. Kara Fitzgerald: Yes, it’s so interesting. I want to say one other thing about it because I just read this recently. Magnesium, sufficient magnesium, dietary magnesium or I’m sure supplemental magnesium is fine, activates … Is associated with increased serum Vitamin D. So it appears to activate Vitamin D. And magnesium deficiency is associated with less Vitamin D in circulation and a higher rate of type II diabetes, so this was looking at NHANES data and they were specifically looking at diabetics but the connection of magnesium being essential for Vitamin D activation was just amazing to me.

Romilly Hodges: That is very neat. And it just goes to underscore just how much these nutrients act together as well. So going back to casting that wide net and looking at things comprehensively, so really, really important.

Another really interesting thing about Vitamin D is we learn in school that Vitamin D is activated from its 25-hydroxy form to 1,25 in the kidney, but immune cells also have the machinery to activate Vitamin D from 25 to 1,25, and that’s not all, it’s really interesting, and cell studies also suggest that Vitamin D can increase all kinds of immune cell activities from oxidative bursts to phagocytosis and chemotaxis as well. And of course we have the data on vitamins, Vitamin D status in COVID incidence and severity, that’s really compelling. And just at the beginning of this year, we’ve had this background association between Vitamin D status and autoimmunity, but this January published this type of study for the first time, a large double-blind randomized controlled trial in fact had 25,000 participants where they took 2,000 IUs of Vitamin D per day for five years and it showed a reduced incidence of autoimmune disease by 22%. So just staggering, and we always talk about how it’s challenging to use the established research model for these multifactorial interventions like functional medicine, but here we are looking at something that is … What’s considered like the gold standard of research and just really compelling in its use for autoimmune disease, so …

Dr. Kara Fitzgerald: Yes, that’s right. I’m familiar with that study. I think it was the VITAL cohort. And that’s a relatively modest amount of Vitamin D. And the other thing, I want to just point out Romilly, like one could hear this, the wonderment of Vitamin D, and think that more is better. If a little bit is good, more is better, and there’s really a sweet spot. We don’t want to overdo it, so we just want to make sure we get our Vitamin D levels tested and that we’re somewhere in the neighborhood of maybe what, 50 to 70 or so? What are your thoughts there?

Romilly Hodges: Yeah, I’m not adverse to that. I do tend to lean more in the 40 to 60 range which is the Endocrine Society’s range, but the IFM goes a little bit higher than that and yeah, what you suggested is a little bit higher. But I still think certainly within a very good range to be aiming for. Certainly I would not want to see it below 40, and the reason also for that is because there’s fluctuation and so you might test at one time and it’s over 40, you might test another time and it’s under 40, so you want to give yourself a buffer zone so that you make sure that you’re within a good range on average at any time.

Dr. Kara Fitzgerald: And benefit from Vitamin D, if somebody is Vitamin D replete, is actually not there. So if you are already taking Vitamin D and you think you’re going to stack some more on to get some of the benefits we’re talking about, if your Vitamin D is adequate, you’ve already got those, you’ve already dialed that in. More will not yield better and I think it’s important to understand that.

I do want to just throw out, being in the epigenetics space these days and biological aging specifically, there was a single study looking at Vitamin D deficient obese African-Americans, and 4,000 IU for 16 weeks significantly reduced biological age by about 1.5 years, which is just another extraordinary thing about Vitamin D, it’s got its influence everywhere.

Romilly Hodges: Right, right. So any listeners are not allowed to get bored by all this talk about Vitamin D, it really is that important. It’s that important, and your point about not getting extra benefits if you’re already replete, I think that’s something that if you see a study that is saying no benefit from Vitamin D supplementation, and you look at the details of that, oftentimes you’ll see that it might be using Vitamin D in a population that is already replete or it hasn’t been measured, what their original Vitamin D status is.

Dr. Kara Fitzgerald: Yes. Yes. Absolutely.

Romilly Hodges: So all of these subtle nuances in the interpretation of research data have to be taken into account.

Dr. Kara Fitzgerald: So I want to ask about other sort of nutrient ahas that you made in your drill-down into writing Immune Resilience. But anything else? Any final thoughts on supporting mucus, on thinking about secretory IGA, on saliva, and also any other thoughts on microbiome health?

Romilly Hodges: Okay, okay, lots of things, but actually, as you said that, I realized that I wanted to mention about glutamine, and this plays into kind of using supplements for more than one thing, but glutamine is actually a really important fuel for your immune cells. It’s actually the main fuel for lymphocytes and its use can be greater than glucose for energy production during illness. So really, really interesting about glutamine being important for immune cells. As far as nutrients go, again I’m going to just paint that broad picture again. Like we have to be thinking broadly. So even cellular energy production, like Krebs cycle nutrients, electron transport chain nutrients, so our B vitamins, magnesium, potassium, iron, coenzyme Q10 and things like that. We have to think about the immune system as something that needs to be able to proliferate, the cells need to be able to proliferate rapidly when we come under attack. So all of the different types of nutrients for cell proliferation is massively demanding, so again, like Vitamin A, zinc, folate, nutrients like that that play a role in forming new cells and then all of the different functions of the immune system, for example like respiratory bursts, we use iron, we use arginine for nitric oxide as well. And antioxidant protection, which is the other side of that respiratory burst, that we want to protect any of the bystander cells from any damage.

Phagocytosis, really kind of intriguing early data on how polyunsaturated fatty acids might play a role in the cell membrane flexibility that you need, that that cell needs in order to be able to perform phagocytosis which is where like literally the cell membrane has to change shape to engulf something else, and so you want some … You don’t want too much flexibility in cell membranes, but you want enough, and so some of the data showing that if you introduce more of those into cell membranes, which we can do by diet, that it improves phagocytosis. And of course we have classic nutrients for immunity as well. Like we think of Vitamin A, Vitamin C, Vitamin E, D. Iron is thought of as well, selenium and zinc, in sort of classic immune function thinking. All of these by the way need to be optimized in advance of an infection because once you’re fighting an infection, all things change, and it’s hard to stay nutritionally replete during that time and then we have all kinds of other things going on like iron is sequestered out of circulation because it can be harnessed by pathogens for their own growth. And one of the sequestration areas is actually in immune cells, so that’s of course handy for immune cells who use it.

What else did we mention? So we did talk about mucus, different types of fiber. I think a variety of fiber is what produces diversity in microbes, so I am for that. And then secretory IgA, right, so probiotics, I did mention that. And then there are other things that are noted to be able to improve secretory IgA production and those would be mushrooms and incidentally beta-glucans are and there are quite a lot of beta-glucans in mushrooms, so it could be that component of mushrooms that’s having that effect. Also glutamine, Vitamin A, echinacea has been shown to increase secretory IgA, intermittent fasting, that’s an interesting one in this context specifically, moderate exercise and yoga, there’s also research there. Did I cover everything?

Dr. Kara Fitzgerald: Yes, this is good. No, this is fabulous, it’s great. I think we’ve got … We’ve whetted the appetite. Folks, Romilly goes into this in the book, and her book is written in plain language.

Romilly Hodges: It is in the book.

Dr. Kara Fitzgerald: So regular people will be able to understand utilize this, but given as you can see her creative thinking and her piecing together supporting immune health from a functional perspective and bringing in some of these new ideas just means that this book is going to be useful and is useful for us as clinicians actually, I read it and I’m thrilled with it.

So you said something compelling that I want to underscore and that is once you’re sick, kind of going back to your foundational nutrients to build immune resilience isn’t going to work. We move into needing different interventions in the face of illness and I think you address … You touched on both and I know that you covered this in the book, but talk about dietary patterns and immune health.

Romilly Hodges: Mm-hmm (affirmative). Mm-hmm (affirmative).

Dr. Kara Fitzgerald: Maybe in both … Like through both lenses. So most of it’s focused on prevention, so put a lot of energy there. But then once you’re actually not doing well, what’s a good diet?

Romilly Hodges: What’s a good diet? Yeah, great question. Okay, so in advance, sort of working on the immune resilience building in advance of any kind of infection, of course we’re going to be thinking about some of the obvious things like we want nutrient density, we want phytonutrient density, we want fiber and things like that and then we want to avoid things that are harmful to our immune system, like chemical additives or contaminants, endocrine disrupting chemicals by the way are obviously known for their endocrine disrupting effects but they actually also target the immune system as well. So we need to be thinking about our exposure to those, and sugars in our diet. Sugars or refined carbohydrates. We know that those are harmful for a bunch of different reasons, but they actually also … It’s also very harmful for our immune system as well.

There was this really intriguing research that came out over the last year or so from the EPFL University, which is the university in Lausanne in Switzerland and there were a bunch of researchers there who had previously been working on the sort of artificial intelligence brain simulation technology that they were combining with cellular and molecular biology and during COVID and what they were seeing was increased vulnerability for those with diabetes to COVID, they pivoted what they were doing in their artificial intelligence and they started looking at mining the thousands of papers that were being published for any correlations between higher levels of glucose and immune function or immune susceptibility to COVID and things like that.

So they published this sort of summary of what they found and they really argued that having higher blood glucose was associated with nearly all the different stages of that life cycle of the virus in the body, everything from attachment of the viral particles to reducing our own antiviral mechanisms. So reduced macrophage function, reduced phagocytosis, reduced chemotaxis again. So really affecting humoral and cellular defenses at the same time, and then also increasing viral replication and then separately we also have a bunch of research that shows how it can disturb tight junctions and reduce our mucus layer and promote dysbiosis, sensitizes those toll-like receptors to be increasingly sensitive to lipopolysaccharides and things that drive inflammation like that.

So this was what they were coming out with and they argued that our airway surface liquid is normally very low in glucose but it’s higher, they were arguing that it’s higher in the patients that are at higher risk and that have glucose management abnormalities. And so it basically summarized that the high viral load is what’s normally required to cause epithelial damage or severe epithelial damage, but under hyperglycemic conditions, even a low viral load could start causing damage as well. So that’s really interesting.

There’s also interesting research on fasting, if you want me to go into any of that and ketogenic diets as well.

Dr. Kara Fitzgerald: Yeah. Just give us a quick survey. Yeah, yeah, because we do … I have other questions that I want to ping you on, but yeah, definitely.

Romilly Hodges: Yeah, okay, okay. So some of the studies have been done in those that practice Ramadan because of their fasting and so studies have been done in those populations. And then there was also a deliberate study done where daylight fasting was used for two days per week for 12 weeks and then they were seeing these rejuvenation-like effects on particularly older immune systems in restoring some of those parameters that they were measuring to be more comparable to the younger participants in the studies as well. And then in animal studies, they’ve seen rejuvenation. Dr. Valter Longo has published on some of these examples where fasting creates a situation that sort of … It triggers the recycling of old and tired immune cells and the production of new ones as well. Other animal studies have shown alternate day fasting for 12 weeks, those animals were better able to fend off infections to salmonella for example, and then ketogenic diets which metabolically are obviously similar to fasting and there was a study done at Yale where they used a ketogenic diet in mice and then introduced the influenza pathogen and the mice that were on the ketogenic diet had better barrier maintenance during the infection. They had less weight loss and increased survival, and they didn’t see this when they used a high fat, high carbohydrate fat. So it was sort of suggesting that the metabolic adaptation to ketosis was most protective.

And I mention that with some sort of emphasis as well, because oftentimes we do see these high fat diets reported in literature as being detrimental and then when you really dig into it, what they’re using is a high fat, high carbohydrate diet which is not at all the ketogenic diet. And so it’s again, the waters are muddied in terms of the research around high fat diets and their effectiveness for all sorts of different conditions. Not least of which is immune function.

Dr. Kara Fitzgerald: That’s fabulous. Yeah, you’re right, and we could have a whole separate conversation around that, but it’s just neat to hear you summarize it and the take home is the benefit of keeping the sugar really, really low and the problems with it getting higher and the utility of fasting and having some ketones. Let’s talk a little bit about lifestyle and immune health.

Romilly Hodges: Yes, okay. So of course from a functional medicine perspective, and even though I’m a nutritionist, a functional medicine nutritionist, we’re always going to be considering these lifestyle connections as well. And some of the biggies would be stress and sleep, both of which tank your immune system. We kind of know a little bit about that from all different areas, but certainly from the research perspective, this tends to be studied in military recruits who obviously we want to keep healthy with the levels of stress and the sleep deprivation they may be experiencing. But they’ve definitely observed that having poor sleep such as less than six hours during a 13-week training, that led to a four times greater likelihood of catching a cold or a flu than somebody who was sleeping seven to nine hours. We see with sleep deprivation increasing inflammation and obviously inflammation is a key immune response, but when it is chronic or if it is in excess levels, then it’s detrimental. And sleep also affects vaccine effectiveness. It’s been shown four hours of sleep for four days before getting a flu shot, only half of the antibodies are produced versus seven and a half to eight hours of sleep. So clearly there’s some impact there, and we all felt this, when we’re particularly sleep deprived or particularly stressed, you tend to be more prone to catching whatever’s going around.

And often, these are the missing pieces. You have that client that comes to you and they say, “You know what? I’m eating so perfectly, I’m just eating a really healthy diet, I’ve cut out everything that’s bad. Why am I still getting XYZ autoimmune flares or whatever it happens to be?” And that’s when these components of the functional medicine lens really come into play, just really, really important. In fact, if you’re in that high stress response mode all of the time, it’s just nearly impossible to elicit the healing response and move somebody through into a place where things can start to get better.

Dr. Kara Fitzgerald: Yeah.

Romilly Hodges: The other lifestyle thing that I think is worth mentioning is around toxins which I did briefly touch on around how endocrine disruptors are actually also … They target the immune system too, but in the earlier stages of COVID, there was really interesting data published out of Harvard T.H. Chan School of Public Health, where they were looking at these correlations between air pollution and COVID rates and COVID severity, and one of the things that they’ve put out there was that for every one microgram per cubic meter of increased air particulate matter, there was an 11% increase in COVID deaths. And around the same time, there were some researchers out of Dartmouth College who were publishing that air particulate matter actually reduces our ability to produce antimicrobial peptides. Remember I mentioned those a little earlier but in connection with Vitamin D, and they actually put out their theory that having a low Vitamin D level combined with this increased exposure to air pollution was kind of like that double whammy that really made you potentially more vulnerable to the infection.

Dr. Kara Fitzgerald: Huh. That’s fascinating. But not unfortunately surprising. Go ahead.

Romilly Hodges: No, that was it on that one.

Dr. Kara Fitzgerald: Yeah. Now let’s see. We’ve talked a little bit about DNA methylation and epigenetics, as it’s right there. And I’ve had multiple thoughts as you’ve been speaking along the way, how intimately everything is connected. Do you have any thoughts that you want to share? Just having worked with me on our Methylation Diet and Lifestyle research and now focusing your lens on immune resilience? Any kind of standout thoughts that you might want to share with us?

Romilly Hodges: Yeah. I think my overarching takeaways from that work and all of the things that we’ve done together really is just how interconnected everything is. So you might pull a thread in one part of your physiology by doing some kind of intervention but really that thread is connected to all different kinds of threads throughout your body, and that really was the impetus for doing the Methylation Diet and Lifestyle research and work in the first place was that we were seeing this … We were seeing the signs in the research, in the literature, and then even occasionally in the patient population of if we’re pushing methylation really hard using high dose nutrients which sometimes is appropriate, but what else could be going on? And so there was the literature coming out around potentially progressing cancer, other kinds of things as well. Because of the connection with DNA methylation and so at the time, the thinking was around mostly metabolic methylation, where pushing the methylation cycles forward for metabolic reasons, but they’re very connected into DNA methylation as well.

So that interconnectedness is one thing and then as a result of that, really how do we best support health in any area was really kind of going upstream and looking to give the body the inputs that it needs and remove any inputs that are getting in the way of what it needs to do, and allowing the body to kind of … To progress in a way that is naturally most healthy and sort of harnessing that body wisdom a little bit if you will. And so those upstream interventions really are dietary and lifestyle, and making sure that you are nutrient replete, that your barriers are healthy and that you’re doing all of those things that create optimal health and so in some ways it can sound really simplistic.

There’s a huge volume of complexity of course in there and a huge amount of personalization because everybody is operating with a different landscape inside our body and around them and so they’re going to have slightly different needs based on that. But it is. It’s this balance between there’s a huge amount of complexity but when you know what the right interventions are, it’s very simple. It can be very simple, right. So that’s the beauty I think of functional medicine as well. But really yeah. If I was going to reflect on my overarching learnings over the last many years, it would be along those lines.

Dr. Kara Fitzgerald: I would say that one of my thoughts when I was reading your book was that we’ve got a lot of shared content, a lot of shared areas to address, sleep, the lifestyle components, stress, the nutrients, whole foods diet, lots of polyphenols, et cetera. So my suspicion is that as we tease out mechanisms of course they’re pleiotropic as you pointed out earlier with regard to the polyphenols but I think that gene expression, the ability for these variables to influence epigenetics, to influence gene expression is what’s eliciting some of these downstream effects that you’re talking about and so I think as we move forward, in this omics era that we’re in, including the epigenome, as we move forward with our investigations and as these tools to look at gene expression and beyond become more widely available, we will see these variables very potently influencing gene expression. I mean ours was the first study to look at a diet and lifestyle intervention but it’s just the beginning.

Romilly Hodges: And it’s really exciting. Yeah. It’s very exciting.

Dr. Kara Fitzgerald: Yeah, absolutely. And this is how we evolved. So yeah, from one vantage point it looks simplistic, but we’re really in this active validation period of seeing that we evolved with these kinds of diet and lifestyle habits or not exactly but with exposure to whole food, with exposure to dirt, with getting some sleep, with resting and digesting, these foundational things really are how we evolved to be and a lot of the sophistication reminds us to go back to the basics, which is just great. It’s just I mean it’s very validating.

Romilly Hodges: It is, it is. And maybe as a last thought as well is that teasing out these threads of complexity, my hope, and I think this will happen and it is happening, it certainly happens in your clinic and the work that we’ve done together, is teasing out those threads that are early signs that something’s dysfunctional. So not waiting until somebody is sick or has a diagnosis, and in immune health, one of the areas that I think deserves more attention than it gets, is those early stages of immune dysfunction that can progress, either through atopic march or adult versions of that, and starting with eczema and the skin barrier that becomes dysfunctional which can of course we now know be a root for sensitization to food allergy and also environmental allergies. But that’s just one example in the area of immune health and of course there are many across all of the different areas. But that complexity that we … As we harness it, we can tease out some of these interventions to look at on an earlier basis.

Dr. Kara Fitzgerald: Absolutely. We just had a Teach-In here on Friday with Dr. Dale Bredesen and that’s how we would prevent Alzheimer’s in the best of all worlds. So just … He was hitting that point home as well and I had a conversation with David Perlmutter and he said in utero is the time you start prevention. Isn’t that amazing? So –

Romilly Hodges: Yeah. I think it’s amazing although it’s hard to know.

Dr. Kara Fitzgerald: It’s true.

Romilly Hodges: I mean it’s definitely true and things, interventions, at that stage would be different than what you might do later on, but yes. And even at that stage, we have to be thinking about how can we set up this individual for their best shot at optimal health?

Dr. Kara Fitzgerald: Yeah, that’s right. And it’s a lot of what you’ve already described. Yes, there’s fine-tuning once an imbalance has been established but polyunsaturated fatty acids and adequate minerals, adequate… full polyphenol diet, exposure to a robust microbiome, a good mucus bilayer.

Romilly Hodges: Yes. Mucus.

Dr. Kara Fitzgerald: All of these things can happen at any time in the journey. So final question on this tour de force conversation, future directions? What should we be paying attention to?

Romilly Hodges: Yeah, yeah. Well certainly the comprehensive and upstream perspective and getting in early with those more early signs that you can do something about. And then really, I think it’s this exciting, ongoing march of artificial intelligence, sort of intimidating at the same time as it is just incredibly exciting for the potential that it presents because I mean there are just new ways to examine these ever-expanding data sets of research that we can’t do in a human level. For example, the EPFL university use of artificial intelligence for the data mining for glucose in COVID that I was mentioning earlier and then also I love this one that you sent to me, research which was recently which was … It was the Institute for Exposomic Research which is a tool for researchers to look at the harmful effects of environmental exposures but not only that, they were focusing on how diets can be used as a countermeasure. So artificial intelligence to help measure that as well and that was through the Icahn School of Medicine at Mount Sinai. So really big institutions looking at this as well.

So I think that’s really exciting and then in the work that you’ve been doing with biological aging and there’s also immune aging, I think we’ll just see this increased ability to use these proxy markers as surrogate markers of health and disease and that will open up new ways to do research in a validated way, especially around diet and lifestyle which normally might take sort of years to manifest effects from but now we can start to see how they impact health in a much more practical and quicker way.

Dr. Kara Fitzgerald: That’s so exciting. I absolutely agree with you, I love it. It is an exciting, exciting time and I do think we need to be leaning on … The time is now to be leaning on artificial intelligence and I’m just really happy that you’ve brought that to mind. All right folks. This has been a fabulous conversation with Romilly Hodges and I just want to remind you to grab her book and go visit Romilly at her website, actually both of her websites, romillyhodges.com and immuneresilienceplan.com. Rom, thanks so much for hanging out with me today at New Frontiers. I’m just thrilled with your work. This direction that you’re going in is very satisfying and important, and just helpful.

Romilly Hodges: Well, I’m hugely thankful for all of the work that we’ve done together which really has been … Shaped what I’ve done just tremendously right from the beginning. So I just appreciate that so much and have loved being on your podcast. Thank you so much.

Dr. Kara Fitzgerald: Absolutely. All right folks. To be continued, Romilly.

Romilly Hodges: Okay.

Dr. Kara Fitzgerald:  As always, thank you for listening to New Frontiers in Functional Medicine, where our sponsors help bring the very best minds in functional medicine, and today is no exception. Not everyone can be a sponsor on my platform, and I so appreciate the good work, relentless research, and generous support from my friends at Biotics, TA Sciences, and Integrative Therapeutics. These are brands I know and trust in my own clinic and can confidently recommend to you. Visit them at BioticsResearch.com, TASciences.com, and IntregrativePro.com, and please, tell them you learned about them on New Frontiers.

If it’s not too much to ask, I would appreciate a thumbs up and a kind review wherever you listen to New Frontiers. Thanks.

Romilly Hodges MS CNS CDN IFMCP

Romilly Hodges MS CNS CDN IFMCP. Romilly is a clinical nutritionist certified by the American Nutrition Association and the State of Connecticut. She is also a certified functional medicine practitioner through the Institute for Functional Medicine. Romilly spent several years as the founding Director of Nutrition Programs at Dr. Fitzgerald’s interdisciplinary, teaching clinic in Connecticut, USA. As well as being a clinician, Romilly has written for peer-reviewed journal publication, textbook contributions, professional training programs, online articles, and has been a speaker at several conferences. Most recently, she authored the book Immune Resilience published in the US and internationally and available now wherever books are sold. Romilly has primary research experience, having designed the first-of-its kind epigenetic study diet for a clinical trial run though the National University of Natural Medicine in Portland, Oregon, now published in the Journal Aging, that demonstrated the possibility of biological age reversal using diet and lifestyle. She has developed successful educational programs for nutritionists and functional medicine practitioners. She also currently serves on the Board for the Accreditation Council of Nutrition Professional Education, a subsidiary organization of the American Nutrition Association (ANA). Romilly has been featured in publications including Mind Body Green, Experience Life Magazine, and The Wall Street Journal. You can find Romilly at romillyhodges.com or immuneresilienceplan.com.

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