Most 'Probiotic' Foods Aren't Actually Probiotic | Dr Maria Marco

0:03What is a food microbiologist? How do you describe the work that you do at UC Davis? So a food microbiologist is obviously a person who's interested in the microbes and foods and that has different dimensions. A lot of food microbiologists are focused on food safety, making sure our foods don't have salmonella or cyclospora. and figuring out how to make foods safe and free of like spoilage microbes so they last longer. And then other food microbiologists like myself are really interested in the good guys, the good microbes in foods. So the microbes that are sort of on foods and in foods and the microbes that live inside us?

0:47That really expands the way we look at food microbiology and thinking about the microbes that are residing in our gastrointestinal tract right now and how food interacts with those microbes. And then go even a step further, what happens after we eat a microbe, right? We see the consequences of that whenever we get foodborne illness. But what about the good guys too? Could we be getting benefits instead of just harm from food microbes? What's the work that you've done to date that you would say you're most proud of or most known for? I started in this area looking at probiotics and whether they're active, whether they can persist in our digestive tract and what they're doing.

1:34And that's still where my heart is, is like when we eat a probiotic or a live microbe, what happens? Does it, you know, die, burst open? Or what I found is actually that the microbe I was studying survived really well, wasn't under a lot of stress. And it was, you know, it may not have lived there very long, but it was active and, you know, eating food and growing. So I think that's kind of where I started and a lot of how I developed my research program over the years. When people hear about live microbes and food, I think a lot of people immediately, their mind goes to fermented foods like kraut and, you know, dairy foods that say live cultures and kombucha.

2:18or maybe immediately their mind goes to the probiotic supplement section of the supplement store or health food store. But in doing some reading of your work, am I right that there are live microbes on non-fermented foods, other foods that we're eating on the daily as well that you've been interested in? So the fermented foods like yogurt, kimchi, and some krauts will have live microbes. And you're absolutely right. So probiotics absolutely need to be alive. And we need those in higher numbers, just the density of microbes to be greater. If we have a salad or we have an apple, there's microbes there, right?

2:57There's just microbes on the plant. And so our diets aren't just with the microbes and fermented foods, but any food can carry a microbe. And again, going back to that safety issue, right? That's how we generally think in a kitchen of how to keep ourselves safe through refrigeration and cooking. but it's been pretty cool to think about like could we just be getting not enough exposure to friendly microbes whether that be on a salad or you know in a higher density in a in a yogurt and so that's kind of expanding the view we have of how microbes could be good for us through our foods at what point does a microbe become a friendly microbe or a probiotic as opposed to just a kind of live microbe that we're ingesting?

3:42Yeah. So probiotics are very specific strains where we know the genome and they have been tested in clinical studies, randomized control trials for a specific health benefit. And that's what we need to look at. We're looking at a probiotic supplement or added to a food and encourage companies put the strain name on there because that's where the evidence lies is with those individual microbes. But when we go a bit further and looking at like a wild ferment from sauerkraut, right, where we could take a head of cabbage, add a little salt, mix it together, put it in a jar and wait. And the lactic acid bacteria, those microbes that give us the sauerkraut are just in like low numbers on the cabbage, but then they grow, right?

4:31And I'm bringing this up because the probiotic strains that have this clinical evidence are different, but still in the same family have relatives in the sauerkraut. So then we kind of go a step further, right? That these microbes, we may not know exactly how they're, if they're helpful for us, but it's kind of a premise to start with. And then when we go a step further beyond that, we look at the microbes on an apple on a head of lettuce, they're going to be different. And we know less about how those microbes could be helpful for us than we would even in a ferment, but they have the components, their cells are recognized by our immune system.

5:14And so that could be like a trigger to cause our immune system to respond in ways that could be more robust when we actually encounter a pathogen. That's a hypothesis, but one that we're exploring. I want to come back to probiotics in a moment. Before we get there, you spent a year with a panel of experts trying to define gut health. So when someone tells you today that they're working on their gut health, someone outside of academia, outside of science, does that mean the same thing to them as it does to you? That's where I started on this whole journey of gut health because I've been using the term and I realized talking with colleagues, or family, right, that we each have a different understanding of what gut health is.

6:01And I was thinking initially more along the lines of digestive health, like symptoms like belching or bloating, right? These are common, you know, all of those many, right? These are very common symptoms. But what became intriguing to me is that, again, talking with others in the field, colleagues, you know, clinicians, that it goes beyond what's happening in our digestive tract and along the gut-brain axis. So our moods, certainly, you know, the sensations of bloating or satiety are triggered in the gut but are signaled through the brain. And then immunity, metabolism. And interesting, a lot of this was being centered back to the gut microbiome, but without, you know, it was kind of scratching my head as to why.

6:44And so, yeah, I spent a year talking with clinicians, dieticians, immunologists, neurobiologists, kind of sorting through this question. can we define gut health? And it was a fun journey because in the end, we could reach consensus on a definition for gut health that was ultimately going to be more expansive than just digestive health. And so give us the definition that you landed on. Yeah, it's a long one, but we can kind of break it down. It's a state of normal gastrointestinal function without active gastrointestinal disease and gut-related symptoms that affect quality of life. And in the paper, you mentioned that two people, I guess, at either end of the spectrum, you can have someone that has inflammatory bowel disease with active inflammation on a scope, for example, but they feel completely fine.

7:36And then the other person has IBS, is in a lot of distress often every day, but every single test that they do comes back sort of clean with no abnormal findings. so based on this definition neither of them has has gut health yeah it's really humbling i mean it shows how far we have to go i think that's one of my main takeaways that we need improved validated functional metrics that we can you know test for somebody who has symptoms but no pathology right so no obvious tests that can be run but the symptoms are real and then vice versa a person that has all evidence of pathology, but feels fine.

8:21Like, why is that? So it's a very humbling kind of call that we need to tackle this. And I think we have the right resource, we have the right tools, and we just need more people thinking about this to get to the right kinds of tests. How do you feel about the common commercial tests that people might be using? gut microbiome kind of tests have become very popular in the wellness sphere i'm sure you've seen that that i think people listening to this will be thinking well hang on aren't there tests that are out there that do tell me if i have a healthy gut i can do a stool test it will tell me what my diversity looks like or it might come back and say you have dysbiosis leaky gut i know terms that you have a lot of opinions on for sure.

9:09Are these objective measures of gut health? And was it looking at the commercialization of these things that kind of prompted you guys to want to define gut health? The tests are, I think we're still early stages, unless there is a pathogen that has colonized your digestive tract, like Plostridium difficile. C. diff. I would use those with real caution. Kind of fun to know what your gut microbes are. That makes you a little closer to them. But one point we really tried to emphasize in the paper is that we don't yet know what a healthy microbiome or health-associated microbiome is. So if we don't know that, it's really hard to prescribe somebody or to say there's this problem or another.

9:57So it's not a clinical metric. It's information. So if you've been listening to me or some of my guests talk about the gut microbiome, you'll know that it thrives on very specific types of fiber and polyphenols and resistant starch, many of which the average person falls short on despite the very best of intentions. That's why Dr. Will Balsowitz and I founded 38Terra, a gut health company where science meets supplementation. An independently conducted 15-day M. Scheim study found that our first product, daily microbiome nutrition, or DMN for short, significantly increased short chain fatty acid production and encouraged the growth of beneficial microbes linked to better gut and metabolic health.

10:42It's a simple daily scoop that you can add to water or your smoothie, no sugar, no fillers, just clinically backed ingredients that make your gut bugs happy. So if you want to support your microbiome in a meaningful science backed way, check out 38terra.com and use the code the proof to save 20 % off your first order. What would it take to, for a, let's call it a kind of surrogate marker, something that is even measured in various studies or on these tests like diversity. And let's say that there, I'm aware of some research at least that suggests there's an association between diversity and certain health outcomes.

11:25But what would it take for that marker to be better supported as a marker of gut health? What kind of evidence would you need to see? Right now, we spend a lot of time in the field describing, like, who's there. We look at some names like fecalibacteria macromancia. These may be, you know, new microbial names that people are starting to know, which is great. But what we really need to be learning, and I think we're getting closer, but we're still steps away is like what are they doing it's not just who's there but what are they doing and that is much more important because although microbes have different names and to some degree of course they have different properties to them it's more important to know like can your microbiome efficiently metabolize fiber or maybe this one you have a microbiome that's better suited for resistant starch as opposed to, you know, inulin, right?

12:25So what kinds of enzymes, what kind of proteins do these microbes have that we have that can give us information on what maybe we should be eating or what we should avoid eating, right? So we're getting away from just who's there, which is a diversity perspective, right, to what they're doing. And for that, we need to look at not the names of the microbes, what enzymes, what is the metagenome, what is the functional component of those microbes. And then connecting what they're doing in particular people to clinical endpoints. So here's an intervention that's acting on what they're doing and leads to some change in pathology or symptoms, subjective experience.

13:11back to your definition of what gut health is yeah absolutely and a clinical endpoint could be symptom right symptomatic or or something broader right it could be to do with weight gain right or how that how the diet or how the microbes translate into something that is meaningful to our health we can't talk about live microbes without talking about probiotic supplements at least five or ten years ago and when people thought about gut health i think the first thing that that came to mind probably was the probiotic supplement and there was a lot of marketing at that time suggesting that for for good gut health take a multi-strain probiotic and probiotics really flooded supplement stores and and the the health aisles of of health food stores how do you feel about probiotics in terms of gut health both in the context of let's say the healthy, normal person with good gut health and function, and then the person that doesn't have gut health?

14:13It's been a ride. Way back when, you know, there was, when I started, there really weren't many probiotics on the market, or you go to the health food store, and now they're really front center in places, you know, box stores. I look at it like this. So you may not notice a difference, right? If you take a probiotic, or you may, right? And a lot of where the science is, is what may work for me may not work for you, right? It's a very individualized response. Personally, I responded really well to a probiotic and I was amazed. I went into it and I wasn't really expecting anything. With personal experience and then just looking at the literature, I see something to this.

14:54I see something to what the concept is, again, getting access to more friendly live microbes in our environment and directly into our digestive tract. So the thing is, again, you have to, if you want to explore probiotics, you're probably going to have to try different preparations, different products. I would always kind of lean towards those companies that have the strain name on their label and have the science to back it up. So there's a U.S. probiotics guide available that has names of probiotics and the clinical evidence studies that support or, you know, have been done for that for those strains.

15:37Is it going to solve all the problems? Absolutely not. Absolutely not. But it's kind of a tool in the toolbox that we could have and we want to use to address aspects of our health. I was surprised by how short that list was given the marketing, the kind of circumstances where there is an indication. Like, for example, for IBS, there are a few probiotics that have proven to be beneficial. I think the list is shorter than most people might presume. It goes to the fact that, you know, companies are going to be looking at their own strain and there may not be the incentive to do the clinical studies in the first place.

16:17and there's so many different reasons we would take it or like what is it to for weight management is it for mood and stress is it for gi symptoms is it for vaginal health i mean there are just so many requests we have for our food for our diet and for probiotics that really i think stretch the research then in some of the marketing people will kind of be exposed to here they'll they'll see wording like enteric coating or slow release how how important are those kind of i guess formats for getting these probiotics to the right place does that really matter i don't worry too much about it but we want them to be alive i guess that's where they've been tested and in the product and some will be more sensitive to oxygen and so they should be protected into the product and maybe kept cool and dry.

17:10But then what happens after we eat them? I would say another thing is just have it with a meal because that's going to increase the pH of the stomach and they're more likely to survive anyway. Are there any things that you see in the media or on social media related to probiotics that would get you kind of shaking your head as a microbiologist? Absolutely. Where to begin? First of all, you know, sauerkraut does not have probiotics. That's just a marketing thing. There could be live microbes in there, but do they even know if they're alive? Right. Explain the difference there between live microbes and probiotics if someone didn't catch that.

17:51Probiotic is a specific strain. It's a specific microbe that has been tested in clinical studies to show to have a health benefit. Live microbes in sauerkraut or foods are just live microbes. We don't know. We have some, you know, associative studies that eating more microbes could be good for us, but like that's really new. So which fermented foods contain probiotics? So you could best likely look at yogurt and then certain companies will put the strain name on there that will be backed up by clinical evidence. And what about kimchi or kombucha, these other ones? No. There's a bacillus strain that, so this bacillus coagulans, it's an endospore-forming microbe that can be put into a lot of foods because it forms this really dormant structure called endospore.

18:42And there's some studies on that particular microbe. I think that's added in. Why is that distinction important? Because you're not saying that kimchi is not good for gut health. I mean, you're studying it, or kombucha is not good for gut health. You were just saying that they often write on the label live cultures, but that's different to probiotics. Why is this important, I guess, to the person at the grocery store, or is it even important? I think it's important for the, I think just saying live microbes or live cultures, live and active, right? You've seen probably on dairy foods, and that's just a signal that these friendly microbes are there.

19:18And there have been thousands of clinical studies, some good, some bad, but there have been clinical studies on specific strains of microbes and shown to have in the end a benefit or at least we have evidence on them and i guess i just gotta say that even though we would have say two e coli you probably know e coli meaning we didn't call right just this is a bacterium two different e coli strains can have different properties really different genotypes and different effects. There's this EHEC E. coli, which is a notorious pathogen. Enter hemorrhagic E. coli causes colitis and kidney problems. And then you have another E.

19:58coli that's just in my body right now. And you know, my gut, it's not doing anything. It's still an E. coli, but they're very different in how they affect us. So that's why it's really important that we know that strain, that probiotic was tested in that study and why we don't want to just believe that if you see probiotic on a sauerkraut label that it's going to be probiotic so you think that we're conflating or brands are conflating live cultures with probiotics and the consumer ends up believing you're consuming a food that contains a live bacteria that has been shown to have a beneficial your outcome, but that is not the case.

20:38That is absolutely true. Yeah. I think it's just, we recognize the word probiotic and we, you know, many will say, okay, there's going to be microbes in there, but I think it could be taken too far to assume that those microbes have been actually shown to have a clinical benefit. Okay. What else is on that list? What else are you shaking your head out in the gut health space? Just using strains that haven't actually been tested in people and clinical studies that's a concern for me just because it's the same species you can't assume that again the e coli example you're going to get the same outcome yeah so just the use of strains that haven't been clinically verified and the difficult part is that at a consumer level this stuff takes time it means you have to you have to look beyond the label and really it shouldn't be like that the food industry and supplement industry should be regulated to a point where the claims need to be consistent with the science but this is the world that we live in and what i'm hearing from you is when we see gut health claims we need to be more discerning where we can and kind of just just understand what is this claim connected to science looking at a particular probiotic or a particular food back to where we were earlier in the conversation and an outcome that we care about.

21:59Yeah, absolutely. And it's going to be, you know, trial and error because I've, again, we can, it's anecdotal. We can just speak from our own personal experience of like trying a probiotic or a fiber supplement. And, you know, we have very different responses to them and just, you might have to accept that one thing's, you know, it's not going to work or if you don't see a difference just to stop and move on. So if we bring this back to the listener, that's, that's kind of hearing this and thinking, gosh, how do I know if I have a healthy gut? What's the, the, the kind of best way for someone right now to know if they do have a healthy gut, because back to your definition, it's, it's possible to be symptom-free, but not have a healthy gut.

22:46So is, is there clues? Is there signs? Is it how regular you are? Is it the, the kind of stool form and shape or what would someone do as an individual to assess this level of their health? That is an important translational piece to this. And primary care clinicians, pediatricians, gastroenterologists are getting these questions all the time, as well as dieticians to add them into the mix, right? And we're all trying to navigate through a wilderness like this unknown or kind of an outer space in a way, like explorers. in this, I would say, kind of black box that we have of our digestive tract.

23:27We know, I mean, not to say we do know a lot about the digestive tract, but obviously what we are exploring is the emerging science with the microbiome, with the immune system, with the endocrine system, hormone synthesis, and how all of these are intimately connected. So I think working with your clinician or your dietician to talk about symptoms is where a lot of we went back to in the conversation and going for a healthy diet. I mean, that's our what more can we do, right? These are the recipes. How important would you say that that nutrition is for maintaining or restoring gut health relative to all of the other exposures that are important out there?

24:12It is central. And it's one of those things we can conceivably do something about. We can't change our age. I can't even, you know, maybe change our stress levels, right? Although we always use these goals or exercise more. All of these things are sound commonplace, but they will affect our health and affect our gut health. And so diet, we get signals all the time from satiety or being full or being hungry or having an adverse reaction to a food. I think where the challenge is, is what happens when we don't have symptoms or we don't feel something. Could we be doing something more? What more should we be doing that will help us not just today, but like 5, 10, 20 years down the road?

24:57and there we can go back to just you know having a whole foods it sounds pretty pretty boring but it's really the best evidence we have for home eat okay it gets difficult at least from a science point of view to to research these things because if you take a healthy group of people and let's say we have a fermented food or probiotic intervention but they don't have symptoms and perhaps they don't have pathology either, right? What are the things that you're measuring in that study that are suggestive of improving gut health? If it's not those endpoints, in that circumstance in healthy adults, are you measuring microbiome diversity or what kind of surrogate markers are actually established and validated as markers that would be suggestive of an improvement in gut health in a healthy person?

25:56Yeah, that's an excellent question and a huge challenge in nutrition studies in particular, right? Where you're not, your target isn't to treat a disease, but to keep healthy people healthy or, you know, people with no symptoms. And so the common thing to do is to try to approach a group that could benefit and we would see a change in a reasonable timeframe. Some folks who are overweight or older or have some underlying symptoms that can be measured, that brings real meaning, I think, to the study. And I think what the bigger picture here is, you know, not only is it hard to define gut health, it's just hard to define health.

26:38And maybe this is something you've talked about, you know, just like, how do we how do we know if we're healthy? A study that most people don't think about brain health until something feels off. Personally, I'd rather look at the data while everything's functioning fine. That's part of why I use function. It gives you access to a set of tests you'd otherwise chase across several appointments. Two markers I pay a lot of attention to, omega-3 index, which reflects your EPA and DHA status. DHA, of course, heavily concentrated in brain cell membranes. And homocysteine, which is consistently associated with cognitive decline risk.

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28:35Mostly in people that are older than me so I do hold this loosely but covering my micronutrient bases with little downside seems like a sensible insurance policy to me. I'm on Iron Maid's scientific advisory board so I've been able to see first hand how Daily Ultimate Essentials is built. 90 ingredients in a single sachet, NSF certified for sport with every single batch, third party tested for over 290 plus banned substances simply mix into cold water and enjoy they offer a 90-day money-back guarantee on the quarterly plan go to im8health.com and use the code simon at checkout for 10 % off your first order plus a free welcome kit that's code simon at im8health.com is coming to mind and i think you you might have cited it is that the fermented food study out of stanford it got a lot press and and i've had guests on my show talk about it and i think it's an interesting study but it's an example of a healthy cohort of people they got either randomized or or i think it was a crossover so there was a fiber intervention and a fermented food intervention and these were people without symptoms so the end points weren't did the fermented foods improve symptoms the end points were inflammatory markers and i think diversity diversity of the of the microbiome and so in that instance, how do you feel about that kind of study design and what it does or doesn't tell us?

30:05Yeah, I love that study, right? Because fermented foods look really great. And I was, you know, matched up against fiber. I mean, it's one study and, you know, appreciate the comment that, right, they looked at immune response and reduction inflammatory cytokines, and sort of better immune profile. I'd like to see that kind of study. So what is the outcome for that person? These are plausible. The fermented foods improved the subject's health. That person didn't feel any different. So it's a critique. But I think I agree with you that that kind of study does point in the direction of what we can learn from studying people without underlying conditions or disease.

30:55It possibly is a stepping stone to a more targeted population. So it's hypothesis generating in that some inflammatory markers did go down. That could be a good thing. It might even be more important in a population that has elevated inflammation to begin with. Yeah. So we're running a study right now with kimchi. So we have a human study. I'm collaborating with a professor in the department of nutrition here, Francine Steinberg. and we're testing to see if kimchi consumption as opposed to cabbage over three weeks affects inflammatory markers so you know we have to have these follow follow-up studies we are specifically though target people who are overweight interesting so that's a what's the control in that study they're doing nothing cabbage just straight up cabbage versus same kind of nap so nap a cabbage because it's a source of fiber.

31:50And, you know, we want to know. So you control that? What's your hypothesis? Yeah, the hypothesis, well, it's a three-week study and it's really the first of its kind in the U.S. Most of these studies on kimchi have really been done in South Korea where they eat kimchi all the time. And we are looking to see if the kimchi changes the gut microbiome and causes, you know, you can see an enrichment of the microbes in kimchi in the stools after consumption and that we're not going for weight loss or lower LDL or something like that because it's a three-week study but we want to make sure we didn't lose people and we wanted you know eating kimchi every day so you still think measuring the microbiome is is important in these studies oh absolutely yeah I think it should be it's a tool right we need to know not just who's there but what they're doing right that's going to be where we find the actual targets for dietary interventions of the gut microbiome.

32:49And then alongside that, what are they making? So we look at the metabolome as well, not just the microbes, but what they're making. And that is what's going to be received by the epithelium, the immune cells, and then absorbed. And what is it, do you think, about fermented foods that is affecting the microbiome in a particular way and the immune system? is it the the live microbes within the fermented foods is what the microbes are doing to that food before you even consume it yeah i think it's both and you keep in mind that a lot of fermented foods we eat the microbes are killed they're removed so that could serve as some models that we could use to separate the two but you know we've looked at just the the brine out of sauerkraut removing the microbes and it's has all these cool compounds that some of them are gut microbes are making and are, you know, known through really cool mechanistic studies to be really important in driving immune responses.

33:45So that's the metabolites. But I can give just another example of maybe, you know, there are benefits from consuming the microbes, like they would can be packets of enzymes. I really like microbes. I don't think of them as packets. But like they are kind of these little capsules of enzymes and compounds that, you know, can be protected as they go into the digestive tract in the cell or be produced in the body that have real consequences for interactions with the epithelium. And what's the relationship there with the immune system? How are these foods affecting inflammatory markers? Yeah, so we could look at compounds like phenolactic acid, amino acid derivatives or tryptophan metabolites, indoles that are sensed by receptors on epithelial cells or immune cells, and that triggers pathways that lead to changes in the kinds of immune cells that would be populating in the intestine or signaling to other parts of the body.

34:48Is it just what's in the fermented food or is the fermentation process, is it removing harmful, potentially harmful compounds from the food as well? Yeah, sure. So I'll just take a couple examples, one being yogurt and lactose intolerant. So the yogurt bacteria make lactase, and they're breaking down the lactose as they grow in the milk to give us yogurt. And then what's pretty interesting is that with yogurt, you want to have the live microbes present with that lactase because it continues to work after we eat the yogurt in the digestive tract. So that's one example of a compound that would be toxic to some people, right?

35:29Lactose. But then you could look at things like plant proteins or breads, like rye breads, that are going to have phytic acid and phytate. This is an anti-nutrient box mineral absorption. And so through fermentation, that's broken down. So there's a variety of examples here of how fermentation will detoxify the food because fermented foods is a pretty broad category do you have a sense if kimchi is different to kraut is different to yogurt in terms of the effect that they're having on gut health be it through the microbiome or other mechanisms because i think we should establish that these foods could be influencing gut health through the microbiome, or at least as I understand it, it could be independent of the microbiome.

36:15So is there a difference between fermented foods and does the individual person's baseline microbiome, which does seem to vary from person to person, matter with regards to the way in which their physiology will change after consuming that food? You're absolutely right that there are many kinds of fermented foods. So it is something we have to be aware of to not over generalize because we talk about chocolate, bread, beer, wine, sauerkraut, kimchi, yogurt, right? You know, coffee even, right? It's, oh my gosh, there's so many, right? And there's different microbes that would be growing in tempeh than in yogurt or sauerkraut.

36:58So just stopping right there, We have different ingredients. We have different microbes. You're going to have different compounds there. What I could see the field going towards is to try to categorize it a bit more. And it may fall along lines of, well, this is a cabbage-based ferment. So there's going to be these common compounds that are microbes, kind of microbes that would be there that have these effects on the body. Just from that kind of categorization. And there might even be crossover between, say, fermented dairy and a sauerkraut. But we know that those two things taste very different.

37:46So it's not too difficult to conceive then that they're going to have different bioactive compounds between them. It really comes down to understanding what are the specific compounds or the microbes that are needed for said outcome, right? that what you're trying to achieve with your health. I'm assuming as part of your kind of lead up to the kimchi study, there was quite a bit of a review of fermented food evidence that's out there. And probably that's where that Stanford study came up and others. But if you were to kind of just get us up to speed, how much evidence would you say would exist today that fermented foods improve gut health per your definition?

38:32We looked at it for fermented dairy foods. And to do that, we went into the human study literature and children, adults, healthy, underlying conditions. And as you can imagine, there's a lot of endpoints that were looked at and we wanted to stay away from probiotic studies because a lot of those used fermented dairy. And what was surprising to me, and I mean, I absolutely did not go into this expecting any kind of outcome, but out of 37 studies, we ended up including majority, fermented dairy had a benefit on what we consider to be gut health. That would be symptoms. And so biomarkers as well would be TNF-alpha and serum and looking at intestinal barrier function, things like metrics that we would discuss and include in the definition of gut health.

39:28So that was pretty surprising. Again, I wasn't expecting that. We know more about yogurt and fermented dairy in health broadly. And you could say that the same for gut health. Now we can say about kimchi or any other fermented food. So a lot of this is going to be trial and error for an individual before we know, you know, have actual bona fide metrics. Or, you know, maybe we will get to actual claims or recommendations in diet. But I think we're inching towards that at this point. So what are some of those, I guess, more established biomarkers that you accepted as a measure of gut function and or pathology?

40:08Well, besides symptoms, which are really important instruments of measurement. And for me, as a microbiologist, right, I'm not speaking as a clinician, but as a microbiologist, that speaks volumes. And then what we use will be pretty fecal and serum markers like fecal calprotectin, inflammation, or we look at zonulin biomarker for some barrier function. And it does take a lot of interdisciplinary approaches to tackle this problem of what we should actually be measuring. yeah i guess the point of my question here is that i'm interested both from an academic point of view but also for the individual who's looking at a supplement or something else that's making a gut health claim if we are saying that said food or product improves gut health and then we were to look at the study and what it did and what it's measuring it sounds like what i'm hearing from you is that some of the endpoints that are being used are not necessarily reflective of an improvement in gut health, like a change in diversity, but other things like certain inflammatory markers or zonulin, which is a marker of intestinal permeability, would be accepted as an improvement in gut health?

41:25Yeah, I can follow maybe even the frustration on this because it is rather unsatisfying because we don't have like a panel, okay, we're going to do test X, Y, and Z, and we're going to say, based on that test, you have gut health, right? So I think we have to accept for now the imperfection of the methods that we have. And I have to just, not to make a disclaimer, but this is really a starting point. And what we're trying to say is that in clinical practice, symptoms, how a person feels is going to be driving the clinician to go, you know, whether specific tests are needed, whether you need to see a gastroenterologist.

42:09And then at the research level, we need to do a better job of saying, in this study, we are looking at this particular outcome on gut health and to power studies for that. I mean, most microbiome studies are not powered to measure a change in the microbiome in a clinical setting, right, where you're looking at treatment of disease. It's really to help the patient not to see a change in the microbiome. So it's added on later. But, you know, I think I share your frustration that we don't have like this panel of tests that's going to tell somebody tomorrow they have gut health. It's really a goal that we're trying to set here, then something we can apply.

42:47And when assessing a product or a claim that's made, if someone was to do that, and you looked at the research, and it was more mechanistic, and it was measuring short chain fatty acids or zonulin, for example, that is a level of evidence underneath or to something to be less certain about than if the evidence was in a similar population to you where there was an improvement in symptoms. Right. I think that's the takeaway. And we absolutely need this evidence to get better to better evidence to reach the best kind of test that we were going to have, hopefully, in the not too distant future. I came in to use this term and didn't even realize I was using it in a way differently from others.

43:33and it's been pretty fascinating to learn that this term wasn't always around it really wasn't in the scientific literature until the year 2000 and prebiotics companies like selling inulin they really found through consumer research that talking about their products in terms of gut health really resonated and now we have this explosion and research on this term and i see it all the time in the supermarket. Maybe I'm looking for that. But I really started to highlight for me how we are using a term and maybe, like you said, mean something different for me than for you. And how can we get some more evidence and strength behind it rather than just being a marketing term?

44:20Totally. I completely agree. It's a pervasive term. It's everywhere. There's claims being made left, right and center. And I just think as an individual, there's not much else you can do other than kind of ascertaining when someone makes a scientific claim having a look at what what type of study that was and is it relevant for you and if there's a claim on an ingredient what did it do is it going to change your subjective experience and are they using the right dose coming back to fermented foods here because i'm conscious that you are you're an expert in these live organisms and fermentation we have the evidence that we have today what do you do as an individual and what do you recommend for your family when it comes to the consumption of fermented foods?

45:05What does a good week look like? Yeah, I think having a diversity of foods, we, I mean, I'll just tell you what I eat, but yogurt is a staple in my household. Cheese, breads, sourdough breads in particular, kombucha, kefir, sauerkraut. And, you know, I feel really privileged that I can go buy these things, but I think they can be quite expensive and, you know, are time consuming if you want to make them at home. It can be easy to make, but they also are time consuming. So what I would suggest is you should eat foods you like and try to get a diversity of them as you would with different kinds of fibers.

45:42And that's what we do. Is there a particular probiotic strain in dairy foods or other feature of dairy foods that that would make fermented food essential to gut health for anyone? Or if someone's not consuming dairy for whatever reason, is there a way for them to get similar exposure to certain microbes or other elements of dairy that you would recommend? Yeah, absolutely. So there are these plant-based yogurts. They have the same kind of microbes that we would find in dairy yogurts. So that could be an option as well as some plant-based cheeses that we see coming up. And water kefir or kibas is very good.

46:25There's plenty of plant-based foods choose not to have dairy. It would be interesting to see if those foods have the same or similar effects on kind of some of these intermediate markers or harder clinical endpoints as well. Yeah, I agree. There really aren't human studies on those foods as there have been on dairy. You know, yogurt, we now have a qualified health claim for reduction of risk for type 2 diabetes but we actually have been looking at plant-based yogurts and comparing them to dairy yogurts and what we've kind of one aspect of this is do the microbes survive in our digestive tract it's a question i get a lot and the answer is yes they do they do survive and they're probably going to survive even better if you have them with a meal like yogurt with a meal but we found that between plant and dairy-based yogurts microbes survive and dairy does a little better but you can have it, you know, plant-based yogurt, you know, that microbes are going to reach the digestive tract.

47:26And what happens to those microbes when they, they get down to, to your colon where you have a whole ecosystem of microbes, some that you've had, you know, for, for most of your life, do these new microbes that are in the food, are they setting up a tent and, and calling that home or are they just passing through and there for a week or two? What does that look like? Yeah, I think most microbes are going to be passing through and unless you have major disruption to your gut microbiome in hospital. But yeah, these microbes are going to be passing through because we have a very stable microbiome in our intestines.

48:05But a couple of things to think about there is that we have a lot of tractable land there in our small intestine. So when we eat a yogurt for a short period of time, those yogurt microbes are going to be really abundant. They're going to be matching the number of microbes in our small intestine. When they reach the colon, they could be metabolically active, making lactic acid, for example, that can be eaten by other microbes and that can have downstream consequences. Or they could be lysed and then their parts are also food for microbes that are there. There's, you know, few examples out there of engraftment or colonization of probiotics in particular, you know, or a little bit less about fermented foods and their engraftment.

48:52But what was kind of interesting there is kind of that pairing going back to the individual of is there a missing microbe that microbe, you know, could maybe fit in a little better because it has space in that ecosystem. I think for most of us, we probably don't want them to engraft unless again, that goes back to this very humble situation we have not fully understanding the microbiome and you know what they're doing for us and those key enzymes those key components we need to keep us healthy so i think for most of us though they're just going to be passing through and when you say the the microbes could be lysed that means kind of like they're they're inactivated killed broken up into fragments is that why earlier you said that sort of dead microbes may still be beneficial and even pasteurization so if we're thinking about a food like tempeh it's often pasteurized you know sourdough is heated so i believe a lot of the microbes would probably be killed is that the the reason you're saying those microbes could still be beneficial because we're still consuming them but it's like the parts of the microbe that end up interacting with our our gut in some way shape or form yes indeed so peptidoglycan which is a term for the cell wall of some bacteria, well, I guess all bacteria, or at least those that we find in food.

50:10And the little parts of peptidoglycan are really unique, not made by our bodies. So they're recognized by our immune system. And those parts would be then in the food or, you know, the dead cells. This kind of brings us to the term postbiotic, which is another biotic that we're hearing more about these days how do you think about balancing food safety with live microbe consumption so earlier you mentioned like a lot of the foods that we eat you know have a salad eat an apple there's the live microbes on those foods which may be beneficial there can also be harmful bacteria on salads and different foods and so where my mind's going here is if we're washing or peeling our fruit and vegetables from a safety perspective are we reducing our intake of these potentially healthy microbes at the same time and is that something that we need to balance yeah absolutely safety is key there are some really bad microbes out there like listeria botulinum you know botox that causes botulism and paralysis, just nanogram quantities of this toxin that gets beyond pervasive in our bodies.

51:30It will kill us. So that is essential. And I'm not too concerned about the effect of like peeling an apple or washing the lettuce, but there's still going to be microbes there. Washing a lettuce is not going to remove microbes. It's not going to remove pathogens either. So all the way back in the field or where we grow or how we preserve foods is so central to the food, that element of food safety. What makes a fiber prebiotic? And when we consume a food that contains prebiotics, in what ways is that affecting our gut health, be it through the microbiome or other mechanisms? Yeah, fiber is a big term and there are many kinds and we'll have some fibers that are easily digested by our bodies, amylases, enzymes that our bodies make into sugars that can be then absorbed or don't go further down the digestive tract, say beyond the small intestine.

52:32and then we have these non-digestible fibers that are not digested by our bodies but can be digested by the gut microbiome and that's bringing us to this term prebiotic which are compounds and it can be fibers but also other compounds that result in enrichment of beneficial microbes in our digestive tract particularly the colon and through their growth the outcome of that is some measurable benefit on our health through like the metabolites they make like short-chain fatty acids are absorbed so there's even other fiber that cellulose that's not degraded at all right and just kind of it's all you pass through so there is ultimately best to have as much fiber as we can and the diversity of fiber for different these different reasons but if you know giving food to our gut microbes is we're increasingly learning how important that is coming back to a food we were talking about earlier tempeh it's a mold-based fermented food and that can be enriched in fiber so molds in their cell wall they have chitin and beta-glucans which are from what we've looking like prebiotics.

53:55So enriching for the beneficial microbes in our digestive tract. It's another great thing about those food microbes. So your overall philosophy when it comes to nutrition and gut health, it seems consistent with everything that I've read and what many guests on this show have kind of said, which is focus on a wide diversity of foods that contain fiber and different prebiotics and try to have a regular consumption of fermented foods. Is there anything else that you would add to that? Or if you had a friend or family member in front of you and said, you know, okay, I got the nutrition dialed. What else should I do for gut health?

54:35Be it to restore gut health or to maintain it? Yeah, the harder things to do. It was hard to have a good diet, first of all, right? To get enough fiber. We hear a lot more about protein recently as well, right? about getting both of these things. And certainly what I've seen also with increasing fermented foods in our diet, the harder, even harder than diet is exercise, sleep, stress, all of these things, which we all want to have going well, but all of these facets affect our gut health as they do our health broadly. That's a goal, right? We could have to have a good night's sleep and to get up and out of our chairs more often.

55:19What are the worst things that someone could do for their gut health? What's the worst? It's kind of the opposite of everything I just said. Eat a diet that's low in fiber. A diet low in fiber definitely has consequences on our symptoms, GI symptoms. And, you know, not eating fresh fruits and vegetables. These are all things just mundane. But I think it's important to know that there is more than just this prescription for healthy foods, that it does not only just affect our body, but affects our microbes as well. And the consequence of those, just bringing this back to Zoom right out, is that when those microbes are not looked after, it changes the metabolites that are being produced, inflammatory markers.

56:05And this has a knock-on effect to different systems through the body. Yeah, we can't, we're not whole without our microbes. So, you know, we're all intimately connected. And that's what's important in our definition for gut health to explain that, or not just the definition, but how we were viewing this term is that the gut microbiome is connected to digestion, it's connected to endocrine, so hormonal responses, intestinal barrier function, immunity in the gut-brain axis. I've been using WHOOP for over six years and I can confidently say it keeps me on track when it comes to my sleep and exercise routines.

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57:36So where to from here for you? You mentioned the upcoming kimchi study, which I'll be waiting for the results of that. We'll share them with everyone, of course. But what else are you working on or your colleagues working on? What are you most excited about that's coming down the pipeline here? Yeah, I'm really excited to see how this extension we have in fermented foods, this extended microbiome, as I'm starting to see it, evolves. There's several signals that are kind of coming up, one being this broader view of live microbes beyond clinically tested strains. And these would be the microbes mainly in fermented foods.

58:19And another is this metabolome or this metabolite-centric kind of view of like what our gut microbes are making is actually kind of similar to what a lot of our food microbes are making in fermented foods. So we have this extended microbiome in our diet, from our diet to our gut. So we're really exploring that and through different ways, looking at the gut microbiome and specific compounds that are made that we haven't looked at. There's this whole like treasure trove, really, of compounds made by our gut microbiome. We have nothing, we have no idea about. So we're busy with that. And then on the other end, going back to the food, what are these metabolites in food from yogurt to sauerkraut kimchi that are affecting our intestines or epithelium and all of the different kinds of cells that are in there.

59:07So it's really exciting to see this kind of come together. And what would your message be to, let's say, a young microbiologist that's in this area of science up and coming is thinking about study design. what do you want to see more of from this field in general that will help help push it forward to to the kind of space where you'd like to see it yeah it's really become interdisciplinary science so it's really important for microbiologists like myself to work with clinicians to work with dieticians immunologists and engineers to tackle these problems but stay true to the discipline too, because a lot of folks are interested in the microbiome, but maybe have no training in microbiology.

59:54And I think we need microbiologists to continue the microbiome science to get to where we are. I think of them as actual beings, as microbes, as whole cells, but not everybody will approach it in that way. I guess I would have to add bioinformaticians and geneticists and biochemists. So it really is a multidisciplinary field now. You say microbes as beings? Talk to me about that. Well, a lot of microbiologists will, you know, train to a specific gene or a specific enzyme and you really go into that. And I think that's very important. But if you see them as whole cells, it's like things that change their environment as they do in foods.

1:00:35Very obviously, they have a lot to teach us. Thank you, Maria. This has been great. Really appreciate all the work that you're doing and coming on and helping us contextualize a rapidly moving, growing area of science that people are very interested in and somewhat confused by. So thank you for coming and helping clarify things for us. Thanks, Simon. There you have it, friends. I hope you enjoyed this episode. If you did and want to stay up to date with future episodes, be sure to hit that subscribe button on YouTube and follow on Apple or Spotify. Finally, thank you for showing up and the effort that you're making to take control of your health.

1:01:15I look forward to hanging out with you again in the next episode.