Embark on a journey through the intricate realm of the microbiome, uncovering the connection between your diet and gut health. Delve into the challenges of studying this complex system, exploring how dietary habits shape the trillions of microbes in your gut. From the effects of fiber and fermented foods to the importance of dietary variety, gain insights from recent studies. Explore the intricate interplay among diet, gut health, and inflammation, revealing surprising ways your microbiome is influenced by your choices and its potential impact on your overall well-being.
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
Embark on a journey through the intricate realm of the microbiome, uncovering the connection between your diet and gut health. Delve into the challenges of studying this complex system, exploring how dietary habits shape the trillions of microbes in your gut. From the effects of fiber and fermented foods to the importance of dietary variety, gain insights from recent studies. Explore the intricate interplay among diet, gut health, and inflammation, revealing surprising ways your microbiome is influenced by your choices and its potential impact on your overall well-being.
Learn more and become a member at www.DrJournalClub.com
Check out our complete offerings of NANCEAC-approved Continuing Education Courses.
Welcome to the Dr Journal Club podcast, the show that goes onto the hood of evidence-based integrative medicine. We review recent research articles, interview evidence-based medicine thought leaders and discuss the challenges and opportunities of integrating evidence-based and integrative medicine. Continue your learning after the show at www. drjournalclub. com.
Josh:Please bear in mind that this is for educational and entertainment purposes only. Talk to your doctor before making any medical decisions, changes etc. Everything we're talking about that's to teach you guys stuff and have fun. We are not your doctors. Also, we would love to answer your specific questions. On www. d rjournalclub. com you can post questions and comments for specific videos, but go ahead and email us directly at josh at dr journalclub. com. That's josh at dr journalclub. com. Send us your listener questions and we will discuss it on our pod.
Josh:C
Josh:So today we are talking about a bear of a paper. Did you read it? Oh man, you son of a All right. So like this is like such a complicated p, and I'm like I haven't heard from Adam yet complaining about how technical it is. He probably hasn't read it. I haven' otally called it. I haven't Totally called it.
Adam:Are there pictures?
Josh:I mean, there's a little bit of infographic, like there's one infographic which is not going to help you with little people and pictures of food. So thank you, Alana, dr Garovitch, for sending probably the most complicated paper I've read all year and thank you, adam, for just leaving me out on the lurch here. But let's talk about this. So this is a really Actually, this was pretty influential for me. I still refer to this in my practice. It was a paper that came out in Cell in 2021.
Josh:So Cell is like a major career defining publication, if you make it in there, out of the Sonnenberg lab, which is this, I think, husband and wife team that are just, I guess it could be like brother and sister, I don't know that are just really amazing researchers and scientists at Stanford in the microbiome. So I think what's so interesting about this is it's one of the few randomized trials we have on the microbiome, on interventions for the microbiome, because everything that we have almost everything we have is observational studies and looking at all this data point. So, anyway, maybe we start with what are your overall thoughts about microbiome diet? So if a patient comes to you and is like, hey, I want to eat a certain way to improve my microbiome. What are the thoughts that come to mind about the science or interventions anyway, then we'll see.
Adam:Yeah, I mean, I think when it comes to the microbiome, it's kind of we kind of throw that term out and kind of don't really know. I feel like a lot of people don't really know what they mean when they're, when they're actually saying that.
Adam:It's kind of like catch all phrase and it's kind of trendy, so people are just kind of throwing it around.
Adam:I think the reality is it's such like a huge topic and from what I've, what I've seen, what I've I've been familiar with, at least from the world of like IBS and IBD where where my background in my meta analysis was, is that we really like can't do too much isolation of organisms and then trying to see, like, okay, if we, you know, if we give this organism, does it have this effect?
Adam:Or if we increase this, what happens here? I mean there's like millions and billions and there's so many organisms out there that if we just give one, you really think that that's going to make like this drastic difference. I mean, perhaps it may, but I mean there's just so much going on there that it's really going to be something that's hard to control. And what we, what we are seeing, just in general, at least from what I'm I'm familiar with going into this paper, is that a diet that's high in fiber, that's very diverse and contains fermented food for the most part, is very beneficial for our microbiota. Increasing the diversity, sort of increasing the resiliency within our gut and just not trying to complicate it too much.
Josh:Yeah, so. So I think, like in general, I think those, those points are good, but it's very interesting, and that's what I was. I was figuring you were gonna say something like that, which is why I wanted to ask you. You know, I think the microbiome research in general is uge, like from a scientific perspective. It's highly professionalized.
Josh:There's so much research out there, but it's also like so highly complex, as you, as you pointed out, and a lot of the research is observational and not intervention, specific and not randomized, and so you know, we have all these tantalizing connections between diversity and this condition or this organism, that condition, and it's sort of hard to piece it apart in a clinically relevant way. I think maybe that's the major take home. So like, for example, it is pretty well established that, like IBD has, like one of the aspects of IBD is some form of dysbiosis, right, that is sort of like part of the trigger in a susceptible individual, right. So like that's pretty well established. But then the question is like what do you do with that clinically, right, and so that you know, that's a big question. Also, clinically, we know that there are many studies on particular probiotic strains that have really good clinical impacts, and we know that. But how exactly they work we don't know right. So there's like sort of all these, all these questions.
Josh:One of the things that I really liked about this study was that it actually was like a messy microbiome evaluation but based on a very specific, like pragmatic intervention, and so they're actually. So I just wanted to correct one thing, so there there are two interventions, so one was high fiber and the other one was high fermented foods and what was so interesting. Well, maybe we'll just kind of walk through the design of the study. It was somewhat somewhat surprising results. But any any further thoughts on like big picture microbiome research stuff at this point.
Adam:I mean, and I did say something about, you know, like clinical data and looking at, like specific strains, there are some products out there that do have, you know, clinical trial evidence for supporting their use. I know that there's one particular one for for IBD with specifically for for all sort of colitis, but not so much evidence behind it for for Crohn's. You know, and it's not to say that if you, you know, make a change to your microbiota, it's going to change. You know a specific thing I think oftentimes we're like, oh, you know, the, the, the gut, brain, access, the gut, this, access the gut, that access, it's like kind of get too focused in on that and then we kind of lose sight of the big, big picture, other other items. Now, yeah sure, you know, affecting the, the, the microbiome can certainly have an influence on other bodily systems, but I think we just have to be cautious when, when we are kind of throwing those terms out there.
Josh:Yeah, I think they get overplayed. I think that's probably what you're getting wh, but was so interesting is like there's also like a lot of cell research, so maybe you're referring to VSL.
Adam:Yeah, yeah.
Josh:Which is like a highly studied multi strain probiotic, high dose probiotic for UC for all sorts of colitis, but there's others as well that have been, you know, multiple randomized trials and there's I mean there's all sorts of strains that have been studied for different conditions. I mean, we've done a lot of research in well, there's like there's IVS, there's also we've done a lot of research in C diff prevention and antibiotic associated diarrhea prevention. So there are very specific interventions where I think the data is there. But again it's like we give this probiotic clinic, patients get better, but maybe we don't know why, whereas here it's like we're going to make this overall diet change and we're going to see what happens. So let me just set the stage here a little bit. So this was a randomized prospective study which again is very rare with microbiome studies, U where you had two arms, 18 people in each arm, so not very large, and essentially one group got a high fiber diet recommendation and the other group got a high fermented food diet recommendation and they were tracked over, I think 17 weeks total. They just looked at everything, like like omics up the wazoo, Essentially these were healthy people and they just wanted to look at what is going on on the microbiome perspective, like from a bacterial perspective, from a protein perspective, from all the omics perspectives, like what are we seeing here when we feed healthy people these different diets? And so for three weeks they just collected data, right, cause that's pretty much like what they were doing and they wanted to make sure that things were stable. Then they did four week rev up of either the high fiber or the high fermented foods, and so we'll talk about what those diets looked like in a second.
Josh:Six weeks of maintenance, sort of keeping you at that dose, and then four weeks of choice. where essentially they said, yeah, if you like it, you can continue, and we're just gonna keep on measuring you, and so there's different sort of advantages to each of that. But let me just speak briefly to the intervention. So, like the fiber, the baseline fiber intake was about 25 grams per day, which is kind of surprisingly high for an American population. o I was impressed with that and they moved that up to I think it was 45 grams per day average by the end of the intervention. So a nice solid increase in fiber quantity. And then fermented foods they pretty much went from an average of close to zero, to an average of just over six servings per day.
Adam:It looks like it's consistent of like kombucha yogurt, kimchi.
Josh:Yeah. So it was interesting like they let the people choose their own into like what they wanted to use. So like some people were like straight up yogurts, other people were like sauerkraut. So it was also kind of interesting in that the approach for that differed widely. It wasn't like everyone had to drink this yogurt drink for 17 weeks type of thing. So I kind of liked the variability that that allowed for. So that was kind of neat.
Adam:Have you ever tried quantifying how much fiber you take in a day?
Josh:Oh, yeah, yeah, yeah, definitely, yeah, that's what I do with patients all the time. So I use like a zillion free apps out there, like my Fitness Pal or something, and I do fiber audits and then so like they collect a normal day or a couple of days and average it and get the fiber readout and then we try to increase based on what our total goal is.
Adam:What do you typically see with Patients? What would you guess as like an average?
Josh:Yeah, so interesting. So based on this study, for example. So just kind of jump around, surprisingly this study found that increasing fiber did not improve diversity, even though they thought that it would and you would have assumed that it would, but it did not. And so I actually I think you know there's value in high fiber diets for all sorts of things, but not, at least according to this, for diversity of the microbiome. And there's another study that I reference a lot in clinic that talks about fiber variety as opposed to quantity and that does seem to shift diversity.
Josh:So what I tell patients is I want an audit on the number of, like, minimally processed plant-based foods that you're getting in a day, and we're gonna work on the variety of it if we're trying to target the diversity aspect, not necessarily the quantity. But what happens, of course, is, as you do, that your grams of fiber will increase. You know, sort of like naturally, and I think that's smart the way they did the ramp up. I don't know if you've ever asked someone to start a high fiber diet overnight? But like they will get cramping, you know, constipation, they'll hate you, bloating. So you have to kind of rev up over about a month, which is what they did here, and then the body kind of adjusts to it. So I thought that was cool too. Look, the thing is we don't do this for money. This is pro-bono and, quite honestly, the mother ships kind of eeks it out every month or so, right? So we do this because we care about this, we think it's important, we think that integrating evidence-based medicine and integrative medicine is essential, and there just aren't other resources out there. The moment we find something that does it better, we'll probably drop it. We're busy folks, but right now this is what's out there, unfortunately, that's it. And so we're going to keep on fighting that good fight. And if you believe in that, if you believe in intellectual honesty and the profession and integrative medicine and being an integrative provider and bringing that into the integrative space, please help us, and you can help us by becoming a member on Dr Journal Club. If you're in need of continuing education credits, take our NANCIAC approved courses. We have ethics courses, pharmacy courses, general courses, interactions, that's on social media, listen to the podcast, rate our podcast, tell your friends. These are all ways that you can sort of help support the cause.
Josh:Cool, so, and then fermented foods. Like I said it was a variety and so what was interesting I mean I think the main take home here was that with the high fiber diet they did not see an increase in diversity. With a high fermented food diet they did see an increase in diversity and a decrease in inflammation. So they looked at all like a zillion cytokine markers and markers of inflammation and they saw a significant decrease in those as well. So that was sort of the main take home is that not all dietary interventions are alike, which I thought was absolutely fascinating. So, like clinical application after this came out a couple of years ago, that's what I do. Like, if I have a patient where I suspect that there might be a diversity issue that's driving some clinical outcome, we will either do fiber variety but not quantity, and or and we kind of stagger it fermented foods and we target what they did, which was about six.
Adam:And even though it didn't necessarily increase the diversity, did it make the current organisms? They are more efficient at breaking down carbohydrates or extracting energy or anything like that?
Josh:Yeah, so that was an interesting take too. I feel like when I was reading it I kind of had like Adam in the back of my head of being like they're bio hacking, like they're P hacking. There's so many outcomes here, it's just insane. So, like a lot of me was thinking like this was so clearly exploratory because it's like a bench top science type of lab. But it was also fascinating to see this deep dive on just like 36 people. But they looked at a lot of stuff, and so I think maybe what you're getting to is like one of the things that they were looking at is okay, are we seeing an expression of enzyme activity, the increasing and what? It was kind of interesting like what they would.
Josh:They there was a few take homes that they had. One was that there's a huge lag in the ecosystem change and so like, for example, while they didn't see like immediate change, once people got to choice level, which was, like you know, more than a month in or so more than two months in, that was when they had like the highest diversity levels, and so, even though people were having less of the fiber or less of the fermented foods because it'd be like okay, we're done with our six. Now if you want to stay, you can. And they did kind of, maybe they do for something like that and yet the diversity was the highest. So they think there's like a time lag which makes sense, like the ecosystem is somewhat resilient to change. And then the other thing was it's not becoming more efficient. So, like when they looked at the high fiber diet they were still seeing residues of carbohydrates in the stool. So it's like essentially the fiber, the fiber was increasing and the ecosystem could not handle it. Like there was still all this fiber that was not getting digested.
Josh:And one of their hypotheses was that if you have a quote- unquote, poor, you know industrialized ecosystem, like it just can't handle an increase in fiber that well, and so you're having this inefficient kind of deal or you just need more time, more than 17 weeks, like that was the other idea. Was this super resilient? And if we were at this for another 17 weeks, maybe we would see statistical significant differences. I mean, yeah, I think it was kind of interesting to see that. You know, you are seeing changes. It depends on the diet, which I guess isn't so surprising, but also, like the gut is changeable, but from diet, but also somewhat resilient.
Adam:Yeah, and I mean, and then you know what I'm gonna say. This is, you know, from a clinical standpoint.
Josh:That was my Adam voice, is like well, how is this clinically relevant?
Adam:Because I mean you can, you can monitor all these inflammatory markers, especially when these are. This is like in vitro, right? This is not. This is not. You know, w e're not seeing any sort of like clinical response to some sort of disease process. These are, for the most part, healthy all healthy, all healthy individuals, yeah and so we're measuring all of these inflammatory markers. But so what? What does that mean?
Josh:Right. So that's the question. And you know, I think they're like, you know they bring that up as a limitation and they're like, yeah, next step is to do it in disease populations. And you know, you can see an argument. We're like, well, if you have an inflammatory condition, and now we kind of know that we have a mechanism on how fermented foods might decrease inflammation, maybe you try that. So I'm curious to see their follow-up studies. But yeah, I mean, this basically just shows that in a healthy individual, you can, you know, pop up their Diversity levels.
Josh:You know, another really interesting tidbit I thought, Adam, was that, with the fermented foods, so there was all this increase in diversity, but so that the assumption is when are those bugs coming from? They're coming from the fermented foods. Right? Like that would be the assumption. It's like whatever weird organisms are in the kimchi that you're eating is like where that diversity, where those attacks are coming from. But it's not. So then they like sequence those foods and then like compared them and it's like made up, like very like a small amount of the increase in diversity. And so, yeah, I'm super surprising and I you know they were saying like it's something about the fermented foods that change the environment, that allow the ecosystem to become more diverse, which I thought was just fascinating. So it really is like an ecosystem shift, not, or more, yeah, more open to an More diverse ecosystem. Then like, oh, we're just throwing, it's like a fancy probiotic, we're like just throwing probiotics at it. Like it seemed to be, kind of different, which was, I thought, super, super interesting.
Josh:And then the other really interesting tidbit from like a microbiome nerd perspective is you know, you never know, like when you run these reports for, for microbiomes, you know you get these reports back like beneath detection limit for stuff. And and then if you were doing intervention like this, all of a sudden you see them and you're like, okay, it's an increase in diversity. But the question is, were those extinct organisms in your ecosystem that were replaced with the food? Or was it that they were just beneath detection and had an opportunity to grow up quote-unquote and to become detected? And that's a big debate in like microbiome world, where it's like, if these organisms are extinct in your system, like they might be extinct forever, right? It might be really really hard to have them grow up again, unless there's very targeted probiotics or something or an FMT. As opposed to like, if some of us are there in small amounts and you can target with fiber interventions and things and apparently maybe fermented foods, you might be able to grow them up and rescue them from the edge of of extinction.
Adam:Yeah, and I mean one question I have, and I don't know if you know the literature behind this? But are there, are we seeing in individuals with you know inflammatory bowel disease? Is there any literature supporting you know either a higher high fiber diet or be a diet high in fermented foods and clinical remission rates?
Josh:I'm not aware of any. I think that would be very interesting, especially with these findings right? That we can decrease inflammation with these fermented food interventions, which I think is fascinating. Yeah, I mean, I think that's the next, if they haven't been done yet. I think that's the next question. Okay, based on these findings, can we look at inflammatory you know you could inflammatory conditions and try out these, these interventions? I have not. Well, I guess the way I use it in clinic, which is many steps removed from the research, at least that I'm aware of, is like, if there's a clinical condition and there's a potential connection with the microbial ecosystem and we have evidence that their ecosystem is a mess or disbiotic or just low diversity, you know we might try, I will absolutely try these interventions. Those are my, my go-to's, you know before, even probiotics, is high fermented foods and fiber variety to see if we can improve diversity. But that's not the ultimate outcome, of course. The ultimate outcome is, like you know, clinical symptoms.
Adam:Yeah, and then on the flip side it's like, okay, well, for some of these like highly effective medications, like like a humira or remicade for people with Crohn's or or Ulcerative colitis, is that changing the, the microbiome, in any sort of consistent way? And then does that change have anything to do with inflammation?
Josh:Yeah, that's interesting, like so the opposite direction. You know, I bet Alana, who asked us to do this paper, would know all that, because A, she's a genius and B like IBD is her world. So, Alana, if you're listening, let us know if there is that lurch out there. I'm, quite curious. I mean, more and more we're learning about these connections with all everything that we take in and its impact on the ecosystem. But yeah, I think you know, I guess the the main take home.
Josh:You know there's a few interesting tidbits here that I think we talked about and I don't think we need to belabor it too much and the. I mean this is like a 50 page paper with like insane methods that I don't think makes sense to anybody besides like molecular ecologists. I think the main take home is this diversity, inflammation picture, the different diets, etc. But again, I think the the most interesting thing to me was, you know there's just so few studies where we're doing this in a randomized intervention way that's pragmatic. That was really exciting and I agree, I think the next step would be okay, let's do this in an IBD population and measure these biochemical outcomes and also clinical outcomes as well.
Adam:Did you think it was interesting that the study was sponsored by big Kimchi?
Josh:Big Kimchi? I didn't look. I'm assuming you're messing with me.
Josh:I don't know that that's a big lobbying group, but you never know. I do know that this team at Stanford has done some really neat research, so we might have to follow up with that in the future. Cool, anything else you want to talk about in terms of this paper or the concept in general? One of the things I did note was they registered their trial on clinicaltrials. gov. We've talked about that before being very important, but yeah, and then just a lot of biohacking, like a lot of outcomes. Their primary outcomes were not statistically significant and so everything that they're talking about was exploratory. And, my goodness, did they explore. Like we're talking probably 100 different clinical outcomes, at least that they were looking at.
Josh:So some of these might be random, some of these might be coincidental. They also don't have a true control, so both arms had an intervention of sorts, so we don't have a placebo control or something like that. So these are some minor limitations. Again, I don't think the purpose of the study is to change clinical practice. I think it's meant to be exploratory and in that way it is quite interesting.
Adam:Yeah, I mean, also to keep in mind, is there's only 17 participants per group.
Josh:Yeah, I think at the end they had 18 per arm or 17 per arm or something like that. Yeah, it's very small. But that's the interesting thing is, when you look at, depending on the outcome, if you have this huge ecosystem data, an omics data, you don't need a huge amount of people to have precision within the individual. But any conclusion that you're reaching on a population level is limited by just the size. But again, they must have run $100,000 worth of tests per person. That's kind of crazy. So, yeah, it would be limited in overall.
Josh:And that's the other thing I'm always wondering about. These ecosystems are so many things impact them and people are so different, and BMI matters and age matters and what your diet matters, and where you are in the world matters, and all these variabilities, and so it's almost like you're probably going to lose the force from the trees on a population level. But I guess that they're interested in on an individual if this is our baseline ecosystem, what is shifting, and is that shift consistent across ecosystems, across individuals? I think that's sort of the main take home there.
Adam:Right, yeah, no, I think it's an interesting paper. I think the concept is interesting from like a pure scientist standpoint, but definitely can't take this paper and run to the hills and sort of justify any sort of like clinical reasoning for a lot of stuff.
Josh:No, I use it for improving diversity. But I have to talk to patients. It's like super limited and even that's a surrogate outcome, you know, essentially right. So well, definitely not essentially, definitely a surrogate outcome for clinically important outcomes. So yeah, it is kind of neat to see that you know we can give them a targeted dietary recommendation. It's like, okay, I want you to wrap up over a month with fermented foods.
Josh:I want you to hit an average of six like and all that just gets to come straight from this paper and it's like when we do that we see that we increase diversity and decrease inflammation. That's kind of anything. Cool, alright. I think that's it. Alana, if you wanted us to jump into the deep science on that, I am sorry, I have zero interest and that is way over my head. Even back in the day, Although, I did have flashbacks, so they did most of the like cytokine research with flow cytometry and then like and that's like what I did my first year at naturopathic medical school. I was in the lab doing flow cytometry on this sort of thing, like looking at cytokine response and inflammatory response and test tubes and ex vivo, I guess. I think that's why people were drawing white blood cells from cancer patients that were taking different interventions and stuff. So I did have some flashbacks to like the flow cytometer and how difficult that work was. But I'm so glad I'm out of the lab. Let me just say that I very much appreciate not being a lab rat anymore, so that's a good life move for me, Josh. Pat on the back.
Josh:Alright, ladies and gentlemen, thank you for listening to us for another episode. We are officially caught up on article reviews, although Dr. Cain did reach out. She appreciated our statin conversation but she was suggesting that, you know, we might want to talk a little bit about potential side effects of statin. So I might need to break from statins, I need to detox from statins for a little bit, but we might come back and try to do like some sort of systematic review if there is one I'm sure there is one on like overall side effects with that could be expected with statins, so that that balance that we were talking about could be more informed for for clinicians. So we'll look around for that. Dr. Cain, if you have anything in particular, send it our way. Otherwise, listeners, send us your papers and ask your questions and we will be back next time on the Dr. Journal Club podcast.
Adam:Take care.