The Gut Microbiome, Aging, & Optimizing Healthspan with Tom Fabian, PhD, CNTP

- Gut health is closely tied to overall health, and as we grow older, the processes that influence the composition and functions of the gut microbiome may also impact our health. Research studies suggest that aging-related alterations of gut microbiota may lead to dysbiosis and increase risk of intestinal permeability, systemic inflammation, and chronic diseases. What mechanisms and pathways may be involved, and what assessment options and lifestyle-based approaches may be valuable for a patient's personalized health strategy to support their gut microbiome and aging with good health? - So, polyphenols, fiber, postbiotics, and then targeted probiotics tend to be the primary ways that practitioners tend to focus on supporting the microbiome. - On this episode of Pathways to Wellbeing, we welcome leading expert on the gut microbiome and consultant and science advisor with Diagnostic Solutions Laboratory, Dr. Tom Fabian, to discuss how the gut microbiome may change over time and how supporting gut function may help extend the healthspan. Welcome to the show, Dr. Fabian. - Thank you so much, Bianca. It is great to be here today with you. - Really happy to have you. So, I'd really love to dive, first of all, a bit into your background. Maybe you can tell us about how you came to be an expert in this very important area of gut health and longevity. - So, it's a really winding road actually, so I'll try to make it short. But essentially, I became interested in health and wellness a long time ago, back when I was actually in high school in my teens. And that was around the time I developed an interest in longevity. So that's sort of where I started. It's like, you know, you would sort of see family members and the impacts that aging was having in terms of chronic disease and reduced function and that really sparked an interest in me to figure out is there a way to go into science and to see if there's something that can be done? So eventually I ended up in graduate school and the focus was on studying aging. So that was really where I started. I kind of had a long winding road. I was in academia for a while and then eventually transitioned to the biotechnology industry and worked for a couple companies there. It was kind of early in the field of aging, so I eventually migrated to functional medicine. I just discovered functional medicine through my interest in health and wellness. Got a nutrition certification. For a while I was seeing some clients in nutrition, but because of my science background, I really wanted to kind of bridge that gap. I was seeing the difference between where we're at with science and research and being able to connect that clinically for functional medicine practitioners. So that's really what led me to the microbiome and specializing in translational science of the microbiome for practitioners. - Very interesting background and pathway, like you said, very winding, but I think we often find that functional medicine providers do have a very winding path to where they end up here in this space, and often it includes both that professional side as well as the personal side. And it sounds like for you that was very similar, you've got the academia, you've got the personal experience, the biotech background, et cetera. And so we're really glad you ended up here. And as we talk today, I feel like our conversation will end up underscoring the fact that gut health and longevity are actually bidirectional, and what I'm saying in that space is that the health of the gut and the microbiome, they actually impact the aging process, which I know that you're going to talk a lot about today. But in turn, the aging process impacts the health of the gut. So I love that we have that bidirectional space and that we're going to be talking about both of those pieces. So, can we start out today, broadly speaking, can you tell us a bit more about how you see gut health impacted by aging? - Yes, so there are some processes that have been pretty well documented. As you can imagine, the process of aging, just like a lot of aspects of health, are very individual, but there are some general patterns that have been found. So when we're thinking about gut health, probably central to overall health and aging in particular is the relation to inflammation. So an increase in inflammation is a pretty widely known factor, not only systemically, that's why it's one of the hallmarks of aging, but even in the gut. So we do know that markers like calprotectin, which is a marker for inflammation in the gut, tend to increase. And then we see some related microbiome changes. And as you noted, all of these tend to be bidirectional. So we tend to see a decrease in what we generally consider to be beneficial bacteria, and then a concomitant increase in these opportunistic bacteria that can have some harmful roles in our health and may contribute directly or indirectly to aging. And then again, these connections between physiology and our microbiome are definitely bidirectional. Another example would be digestion. So it's very commonly found in aging that overall digestion can decrease with aging. So that's primarily the secretory functions. So hypochlorhydria and even achlorhydria are more common during aging, and that can affect the microbiome. We know that there are changes in the intestinal barrier, which I'm sure we'll want to get into. That's pretty well documented. And then we know that sort of downstream of digestion, that can have further impacts in terms of increasing these not so good microbes, the opportunists. And then lastly, I would say motility is another big factor. So, slow motility or constipation is actually quite common with aging. And I think some of the stats that are out there have found that roughly 33% of individuals 65 and over have constipation. And again, that's another one of those two-way interactions where the microbiome can play a role. But also slow motility itself can affect the microbiome in a negative way. - So you mentioned multiple areas here. I'm picking up on motility, potential motility dysfunction, inflammation, increased inflammation, you also talked about digestive processes, and then you talked about the dysbiosis. And so, in thinking about this from the healthspan, longevity perspective, I think many people just feel like that's going to be part of the aging process, that just happens, there's nothing I can do about it. Can you tell us, is that really true, or could these actually be modifiable hallmarks of aging? Do they have to happen, or do they have to happen at such a high level? - That is a really good question. So, once again, it is very individual, but certainly learning from practitioners who are actively practicing in this area and applying functional medicine principles, we do see that a lot of these changes can be modified. So, the microbiome is probably one of the most modifiable parts of that picture because we know that's sort of the interface between our environment and our physiology, particularly through diet. So, it's well documented that dietary approaches, especially going and sort of moving from sort of the highly processed standard American type diet towards a healthier whole foods diet that includes additional fiber can really shift the needle in terms of the microbiome, the products that the microbiome produces, which is how the microbiome has an influence primarily on our health, and then therefore that can have an effect, a positive effect on many of these functions that we had talked about. And again, because it's two-way, we know that there are ways in functional medicine to support processes like inflammation, digestion, support the intestinal barrier, which in turn then can help improve the microbiome. - I love that. I love how, again, we're looking at it from both sides of the fence so to speak. Now, you talked about some of the processes that the gut's microbiome supports or has an impact on, specifically there's things like short-chain fatty acid production, bile acid metabolism. Can you talk to us a little bit more and in more detail about how the microbiome composition and the gut functions potentially impact those areas and again, how that then would impact our healthspan and longevity aspects? - So that's a really good question as well. I mean, it really gets at the core of these interactions in terms of current research that we know can mediate some of these impacts on aging. So, when it comes to the microbiome, it's always helpful to start with an understanding of the microbes themselves and how they change. So, at a high level, as we talked about, we tend to think of the core microbiome as the commensal microbiome, the beneficial microbiome. They're known to produce a wide range of beneficial products. So that would include short-chain fatty acids, converting bile acids into secondary bile acids, and those secondary bile acids have really important functions. And then there's a wide range of other beneficial metabolites that have been documented. And then at the other end of the spectrum are these opportunistic microbes, the so-called bad microbes or harmful microbes. They potentially can produce factors, some of which are well known, such as lipopolysaccharide, or LPS, that can contribute to inflammation. And then there are a number of others. So, just to give a couple of examples of how these dots can connect with age, so we know when you have a decrease in these beneficial bacteria that produce short-chain fatty acids, for example, butyrate is probably the best known and best characterized of these short-chain fatty acids. It's widely documented to play key roles in supporting intestinal barrier health, promoting the immune cells that restrain or reduce inflammation, particularly the T regulatory cells. They also can affect various metabolites or various processes that are involved in metabolism, such as GLP-1. There are actually receptors in the gut that respond to these short-chain fatty acids and then can produce and release GLP-1, which we know has metabolic benefits. So, that's just one example. There are quite a few more that I'm sure we could go through as well, but really a wide range of impacts both on the positive and negative side. And as we talked about, there are ways to shift that balance. - Fantastic. So, as you noted, you're looking at connecting these various dots. And what I hear you saying is that the potential gut dysbiosis in that pathway can lead to things that increase inflammation and potentially chronic disease processes down the road, thus reducing healthspan. Can you go into more specifics on what some of those age-related dysfunctions outside of the intestinal tract might look like or how someone might recognize that a particular chronic disease could be traced back to the gut dysbiosis? - Yeah, that's a very good question. So, I think probably the best defined scenario so far in terms of the systemic impacts, particularly in the context of aging, would be this chronic systemic inflammation. So, there are a number of potential sources of this inflammation, with the gut microbiome being one of them. So, in terms of assessing the microbiome, which can be done with comprehensive stool testing where we can look at not only the microbial markers but also intestinal health markers, particularly those for inflammation, one of the most common ones would be calprotectin. Recent studies have shown that in general, calprotectin in the gut can be a marker for this increase in age-related inflammation in the gut. Then if you're looking at your patient's broader picture from test results, of course it's pretty common to look at other inflammatory markers, such as hs-CRP, or high-sensitivity C-reactive protein, as a way to assess systemic inflammation. And those two often are connected. So, if you're starting with your general assessment of a patient and you know from your assessment that you suspect that they do have some sort of inflammatory scenario and the blood work reflects that, stool testing actually can give you some great insights into the potential contribution from the gut component. - Fantastic. So we can look at it empirically, we can look at it from a clinical perspective and say, most likely, there's some inflammation potentially coming from gut dysbiosis. We need to really go downstream, or I should say upstream and really get to the root cause of it. We often see though that patients do want to see some sort of clinical testing and assessment, right? They want to know what is actually happening and it's really great for us from a practitioner standpoint, too, for tracking and recognizing exactly where we need to step in. Now, when we work, when we actually ask for these labs and these assessments, how do we then, as practitioners and clinicians, translate that into the clinical application for recommendations from lifestyle-based therapeutics, maybe botanicals, and maybe down even into pharmaceuticals? - So, in order to kind of translate what you're seeing with gut testing and just kind of your overall patient assessment, it really does start with the assessment, and especially collecting key information. So, as we talked about, just generally looking at their inflammatory scenario can be important. There's a lot of other things that, of course, you may want to look at, but one of the things that's often overlooked that I think is important to include in assessment in terms of interpreting microbiome results would be the transit time. So, recent studies have shown that transit time has a big effect on the microbiome, and it's a two-way interaction, like a lot of things, but we know that there are specific signatures, for example, constipation versus looser stools. So there are just certain things you want to make sure you're noting in particular in your assessment. So that can help you kind of position yourself for better interpreting the results of a test. But once you see test results and say a common pattern that we see with chronic disease as well as with aging would be a decrease in certain beneficial bacteria. The best documented changes with age tend to be in terms of a decrease in the short-chain fatty acid producing bacteria, and again, especially the butyrate producing bacteria. So, bacteria such as Faecalibacterium prausnitzii have become well known, Roseburia, similar microbes that are well known to produce butyrate, that can give you a clue that these are potentially lower than they should be in a given patient. And especially if you're seeing that this patient does have an increase in inflammation, that could be one of the connections there. Then with additional testing, it is possible to look at the individual metabolites that are produced by the microbiome to see not just sort of predicted, in terms of predictions what they may be producing, but what are they actually producing by looking at the metabolites, say, in stool. So that would be another direct way to look at some of these metabolites. Once you know that these are out of range and essentially for a given patient not in optimal ranges, there are pretty well-defined approaches. So, just to outline kind of an easy mnemonic to remember for those approaches, we call it, I tend to call it the four Ps for: prebiotics, which is fiber, polyphenols, which I think our field is pretty familiar with in terms of their many benefits, probiotics, again, those are very commonly used to kind of help complement the microbiome and provide functions that may not be there. And then the last one is a newer category which we're starting to hear more about, and it's sort of a general category called postbiotics and microbial products. So that would include certain probiotics that are referred to actually as postbiotics because they're not live probiotics, but then there's a wide range and a growing number of these products produced by the microbiome that if they're deficient, we can supply those potentially as supplements. So, a classic example would be butyrate itself. That is becoming a much more widely used supplement to support gut health. Of course, the diet is the best source for fiber, but you may want to really target fiber for certain patients that may have issues with bloating, for example. We know that fiber can make certain symptoms for some patients a little bit more kind of problematic. So that's really where polyphenols can come in as well. They're less likely to typically provoke certain gut symptoms. So, polyphenols, fiber, postbiotics, and then targeted probiotics tend to be the primary ways that practitioners tend to focus on supporting the microbiome. - Thank you for that, Dr. Tom. So if I could summarize a little bit here, and please jump in and correct or add to the comment, is we're really looking at creating almost the appropriate soil, if you will, with the prebiotics and then we're feeding, right? We're really adding in the things that the beneficial bacteria would need to survive and multiply, and then we're supporting long-term stability and maintenance within the GI tract. Would that be a good analogy there? - Yes. Actually, the concept of supporting the terrain, I think, has become more widely recognized in our field, and I think it's really appropriate, because traditionally, even in research, they focused kind of in isolation on the microbiome because it's sort of a new science, up and coming science, and they didn't really know a lot earlier on about these connections with the environment in the gut. Since then we've learned a tremendous amount about how important that interaction with the gut environment really is, so that gives us additional ways to support the microbiome. One of the examples I think is becoming more recognized, and I'll just kind of throw this one out there because it is one of the factors that tends to decrease with age, and this is kind of part of looking at the barrier in a bigger picture beyond just leaky gut, is the mucus layer. So we know that that's a really important layer to kind of keep the microbes where they're supposed to be, a little bit of a distance away from the intestinal lining so they're not basically stimulating inflammation or overactivity of the immune system. We know many ways now in which mucus production can be supported, and they're covered largely by what we just talked about. Polyphenols and also fiber are well known to help support mucus production. In terms of probiotics, there's a lot of focus these days on some of these keystone species like Akkermansia. Akkermansia not only thrives in mucus, but it releases factors that can promote mucus production. Mucus production, as I mentioned, is something that's been shown to decrease significantly with age, particularly in animal models where they've actually shown that supplementing with Akkermansia can actually help to improve that mucus layer. And then lastly, kind of a newer connection that is being recognized in research and is just starting to be recognized in functional medicine is the microbiome mitochondria connection. So, it turns out that that whole mucus production scenario and just generally the health of the intestinal lining depends on healthy mitochondrial function. And that's again really where butyrate is such a key factor, because most of the energy provided to those colon cells, including the ones that produce butyrate, or produce mucus, really is dependent on the butyrate production. - You know, as I'm listening to you speak, I'm recognizing that a lot of the foundational pieces of health are truly at the base of maintaining a healthy gut microbiome. And if we're thinking about the nutritional aspect and then we're thinking also about lifestyle components, and so beyond nutrition, I'm curious if you have seen or found or what that interaction is between additional lifestyle components and the maintenance of a healthy gut microbiome, which of course moves on to the larger healthspan. Do you see interactions there with stress modification components, with exercise and movement? Can you tell us a little bit about how those pieces fit into the big picture? - Yes, absolutely. So there's a growing amount of research showing that excessive stress can have a negative impact in many ways on the gut. We know it can suppress digestion, and that of course indirectly can affect the microbiome. We know that stress through direct and indirect mechanisms can cause leaky gut. And then there are other mechanisms that have been recently identified showing that stress, chronic stress in particular, can be a contributor to gut inflammation. And then inflammation in the gut kind of has a two-way interaction with these opportunists, so then they can further amplify the inflammation once they sort of become overgrown. So, stress can be a trigger. It's actually been shown to be a trigger, for example, in IBS, that it can basically reduce oral tolerance and increase the incidence of reactivity to foods. So, kind of from a negative standpoint, we know that excessive stress can have multiple negative effects on the gut. Then stress reduction also can have kind of the opposite effects as you might expect, particularly in focusing on that parasympathetic connection. And the vagus nerve has been a big focus, I know in recent years, and ways to stimulate the vagus nerve have been shown actually to improve dysbiosis in the gut. So, that's certainly one. And then in terms of exercise, a similar scenario, a lot of studies have shown that exercise is one of the major factors that can help promote healthy gut balance essentially. It really goes a long way towards helping to promote proper digestive function, so indirectly supporting the microbiome. But they've also found that with exercise, there is an increase in a lot of the beneficial bacteria. So lots of great adaptations in the gut that can really support a healthy microbiome along with adequate exercise. - Fantastic. Again, just underscoring the profound impact on our daily habits and activities and how those interact at the very tiny level, all the way down into the gut microbiome, and then again, how that impacts going out to our longevity health span and lifespan in general. So thank you for pulling that all together for us. And as you think about your patient experiences, your client experiences, have you seen in general, are there general patient examples or patterns that you could share with us that you've seen in clients either that you consult for or practitioners you consult with that have been able to improve their microbiome diversity measures and how they do that, and what you might see even on labs or assessments? - Absolutely. Yeah. So I would say kind of going back to our discussion around the common patterns that we see with aging, we did talk about that typically with normal aging, or even what we would consider to be unhealthy aging where patients are more susceptible to chronic diseases or may even start to develop chronic diseases, we see an increase in these opportunistic bacteria in many of those patients. Studies actually show that that can happen years in advance before symptoms even start to materialize for certain diseases, such as inflammatory bowel disease, neurodegenerative disease. And then the flip side is we also see a decrease in many of those beneficial bacteria kind of across the board. So, I do have kind of one sort of patient example in mind where this patient was in her 60s, had a chronic condition, Crohn's disease, which she had been managing for probably 10, 20 years in that range, and had been able to manage it pretty well with the help of functional medicine. She had been working with a functional medicine doctor, but then in recent years had found that her symptoms seemed to be progressing a little bit more. So her physician decided to run a comprehensive stool test, and we did kind of really scrutinize those results along with the addition of looking at the microbial metabolites, which is the functional output. So, when you mentioned diversity, some tests can really look at the diversity aspect in terms of the microbes. Other tests really focus on sort of the key microbes. But when you look at the metabolites, especially kind of the metabolome of the microbiome, you're looking at the functional output, the functional diversity. So, this patient had a lot of dysbiosis, a lot of imbalances in her microbiome, along with certain intestinal physiology imbalances, especially leaky gut was a big one. When we looked at the functional diversity, so this is short-chain fatty acids, bile acids, a lot of deficiencies and imbalances there. And that's really looking at a deeper level of functionality. So we know that to some extent, your microbiome can sort of withstand certain changes, certain factors that may impact it negatively, like antibiotics. If you have a good sort of foundation of functional diversity, you can bounce back from that more readily. That's what research is showing. So looking at the metabolites is kind of a deeper way to look at that and see, are these changes really having a big impact on the functional diversity? So that's really one example where this patient did have a lot of imbalances and those specific identified imbalances helped the practitioner kind of zero in on how they could better support their patient. And then I have another case in mind, which is an individual also around the same age, otherwise very healthy. Was really looking to just continue maintaining their health with age and optimize their health, of course, with aging as well. So, again, we looked at the big picture, microbes, intestinal health markers, and then also the metabolites, the production output of the microbiome. Overall, this individual's microbiome looked pretty healthy, just a couple minor imbalances. The main intestinal physiology imbalance really had to do with digestion. And there was a sort of mild to moderate reduction in say pancreatic function, which we know can impact the microbiome to some extent. We looked at the overall microbial metabolites and everything was really well balanced. So, this is a great example of this individual had a pretty solid microbiome. There were a few minor imbalances, a little bit of an issue with digestion, but it hadn't yet really impacted that underlying functionality. So that's really where the idea of functional diversity I think is really important and kind of one of the factors that we're moving towards as a field to look beyond just the microbes and look to what are the functions? What are the products that they're producing? - Thank you for that, Dr. Tom, especially those two different examples that we're able to see, like, we were talking about the patterns of what we're starting to identify when we're sitting across from patients and what potential outcomes are for them. Now, we also know that with these assessments, we're able to drill down. You talked through that, right? We can get really deep into some of the layers of what's happening, and as you said, it really helps us to focus in on what appropriate recommendations and therapeutics we should follow. Now, what about the patient population that either doesn't have access to assessments, or for whatever reason is unable to get a test or an assessment that really does drill down into those various levels? Are there things that we should be looking for and assessing without those labs as practitioners that would help us to continue to home in on the appropriate pathway to support the patients? - That's a really good question. So there are some ways that you can potentially support patients who may not have the benefit of the insights from the testing. There are a lot of general principles that have emerged from the research in terms of kind of what to look for, for imbalances that may be related to the microbiome. Certainly, we know that if you do have systemic inflammation and there's not another obvious source, I think we all know that roughly 70, 80% of the immune system is in the gut. So that is a common source of inflammation. And through an assessment, you can identify a lot of the potential factors that may be contributing to an imbalance, everything from focus on processed diets, you know, if patients are consuming sort of that type of diet, a lot of room for improvement there, and that's probably number one on the list. I think we all know that just moving patients from a not so good diet full of processed foods to one that contains a lot more of the whole foods that are higher fiber, polyphenols. So we can go off of a lot of things that we already know, and I just mentioned the stress example, patients with a high stress scenario, especially if they do have gut symptoms, we certainly know there's a lot of benefits to trying to help them reduce their stress. So, I think based on what we know in terms of lifestyle factors, of course, sleep, we hadn't touched on sleep yet, but we know that sleep and circadian rhythms also have a huge negative impact on the gut when they're out of balance. So lots of things that we can work on without necessarily knowing the details. But knowing the details really does kind of give you that extra layer where you can more personalize your approach for a patient. Otherwise, there's a lot of information on more general approaches. - That's great. Well, thank you for summarizing how we can look at this from a general approach, how we can really focus in on those modifiable lifestyle factors to support our clients and patients, and recognizing that we can jump in when we're already seeing things in terms of chronic disease processes or inflammatory based conditions when patients are coming to us, but we also have the potential potentially to prevent, right, by really focusing in on those lifestyle, modifiable lifestyle components ahead of the disease processes being viewed through assessments or even empirically. So it feels like that base of foundational lifestyle components is really important, and specifically of course the nutritional aspect, but then of course the stress, the movement, and of course, as you were noting, the sleep components are things that we can do in our visits pretty much every time that we can start to hit on all of them or a few of them based on the patient presentation, their needs, et cetera. So, Dr. Tom, I'd like to have you take out your crystal ball and find out a little bit where do you see this field going in the next five years? What new things do you foresee we will learn or that we will dive deeper into, or maybe even some new tools that you might see on the horizon coming to our offices soon? - Yeah, that's a really interesting question. So, it's also, I think, just interesting from the standpoint of trying to figure out based on where the science is now, where the methodology is now, kind of where the trends in our field are now as well in terms of the focus areas. So, I think if you're looking at functional medicine overall, I know that a big trend in functional medicine over the years has been to really focus more on the big picture, sort of the systems biology viewpoint, and I think that's really where we're going to continue to go more and more in that direction as we have more research helping us understand these connections at a deeper level. So, when we're looking at the gut, one of the trends that has come out of research really is that kind of looking at this as a whole, that we need to not just look at the microbiome. I know there's a lot of focus these days on the microbiome and what can be predicted from the microbiome, but it's really difficult to interpret that fully without knowing not only the patient's overall health, but certainly their gut health. So having access to those additional markers and just additional information around gut health can help you interpret the microbiome. Again, it's all based on these sort of two-way or multi-way interactions. So, definitely, I think this systems biology-type perspective is just going to continue to evolve. And then when it comes to the microbiome specifically, there's kind of a big trend towards moving towards beyond just identifying specific microbes and microbial associations. That's been a big part of the microbiome research over the last 20 years, is identifying which microbes tend to be more predominant or less predominant in certain disease conditions, which is important to know at some level. But we also want to know exactly what they're doing in those scenarios. And that's where this growing focus on functionality, microbiome functionality, microbiome functional diversity, I think is so important. There are multiple ways to assess that, but in research, it's considered to be one of the best ways to look at that through the metabolomes, the metabolic output of the microbiome. So I think that's one of the areas where we're going to continue to see an evolution in testing options, focusing on functionality. And then lastly, I think there's going to be, probably with AI, of course, that's really going to be a great tool for helping us put all this together, because that's of course a lot of data, a lot of additional testing results that practitioners may have to take into account. And it's really hard to figure out, you know, so many things are context dependent. It's really hard to remember all those different contexts. So I think we're going to see an evolution of tools that are able to help us bring that picture together better based on the evidence. - Thank you for that. It does make sense that as we drill down and get more data, more information, that we will need to be able to synthesize it specifically for each person that's sitting across from us, right? Because we also know that this is very individualized per person, ethnicity, demographics of all sorts, and that this AI component could really support the pattern recognition based on the patient population. So, it is a really exciting time to be able to bring together those foundational pieces along with the advanced tech that we're all walking into, actually running into very quickly. So thank you for pulling those different dots together from the different fields. I've seen also just in the last while how fast things are coming together. And so, to know that we'll be seeing that in our offices very, very soon, if we haven't already, in various forms, we'll need to be ready for that, but also recognizing it gives us a leg up to really support the individualization and personalization of therapeutics for our patient populations. Well, Dr. Tom, as we bring this episode to a close, I'd love to find out from you what is your one big takeaway regarding the gut microbiome and healthy aging and extending our healthspan? What would you give to our audience? - That's a really interesting question. So, one of the things that we kind of, I think we touched on a little bit is this sort of bidirectional effect of the microbiome and how it interacts with our physiology, which is at the core of health, the core of various diseases, when things are out of balance, they can be out of balance on both sides. And that's certainly true in the aging and longevity field as well. So I think kind of bringing it back to this systems perspective, we're looking at these imbalances, and to your point, even looking early on, what imbalances do we see that maybe don't yet correlate with symptoms, but as we're gathering more information and seeing that some of these changes can be predictive of future risk gives us a lever to potentially work on for individual patients. So I think that's kind of the key, is just trying to keep in mind that big picture and all these different connections, and that for one patient, their weak point might be the inflammation scenario. For another patient, it might be their intestinal barrier that we want to focus mostly on. For other patients, it certainly may be just more their lifestyle factors that need to be adjusted and improved. So there's a lot of potential, I think, in sort of learning more about this systems view because that gives us more areas that we can potentially intervene for individuals. And within that context, we know that there's this growing focus and recognition on the various gut axes, the gut-brain axis, the gut-skin axis. So, another kind of key point, I know you mentioned just one, but I'm kind of working in one more here, which is thinking of kind of when you're seeing a patient, for example, that maybe their skin health is not so good. We know from a lot of new research that actually the skin affects the gut and the gut affects the skin. So, kind of looking at both scenarios. So, it kind of, again, broadens our lens for what we want to look at to support patients in terms of their overall health as they're aiming to have a longer, healthier healthspan. - That is very exciting to me to think about every time we think we know something, it's actually just a start, right? And for people like you who are continuing to look into the next level, the next level, and how does it interact, and how does it synergize with all the other pieces of not just our individual person, but our environment, our community, and the just the expansiveness of all of who we are. So, I'm really grateful to you today for your time, your experience, and your expertise. We look forward to continuing our work together and also working in this space to bring healthspan and optimization of it to our patients and clinicians. So, thank you very much, Dr. Tom. - Thank you so much, it's been a great pleasure to be with you here today. - [Bianca] Thank you for listening to Pathways to Wellbeing. To learn more about functional medicine, visit ifm.org. The future is functional.