What is the Best Diet for Your Gut Microbiome?

Dr. Hedberg: Well, welcome, everyone to “Functional Medicine Research”. I’m Dr. Hedberg and I’m really looking forward to my conversation today with Dr. Lucy Mailing, PhD. She is a microbiome researcher, educator and passionate scholar of integrative, evidence-based gut health. Lucy received her bachelors in biology from Kalamazoo College and her PhD in nutritional sciences from the University of Illinois where her graduate research focused on the impact of diet and exercise on the gut microbiota. She has authored numerous peer reviewed journal articles, regularly presents at national, international conferences and was named an emerging leader in nutritional sciences by the American Society for Nutrition in 2017. Lucy is the founder and sole author of lucymailing.com, a website dedicated to integrative, evidence-based articles about the gut microbiome, health and nutrition science.

Dr. Mailing, welcome to the show.

Dr. Mailing: Thanks so much for having me.

Dr. Hedberg: Great. So you’ve done some great writing and research on some topics that a lot of people are interested in. That’s why I wanted to have you on. So why don’t we begin by really focusing on diet and the gut microbiota and what the research is really showing at this point? So why don’t we start with one of the very popular diets out there which is the ketogenic diet and we can kind of lump in just the high-fat diet in general with that. So what can you tell us about high-fat diets, ketogenic diets and how it affects the gut microbiota?

Dr. Mailing: Sure, yeah. That’s a great place to start. I think one of the key things to keep in mind here is that we’re still in the infancy of microbiome research and especially in our understanding of what constitutes a healthy microbiome. And we have certainly done a number of studies looking at how diet can impact the microbiome. A lot of this has been done in animal models where we can essentially really control the diet of the animals and determine what effects that has on their microbiome. So a lot of the studies with the high-fat diet in the literature are kind of misleading because they’re labeled as a high-fat diet but they’re really more accurately a diet that is very high in refined fats and also high in refined sugar and low in fiber. So we can’t really take that and compare it to the equivalent of a very healthy, like a health-conscious ketogenic diet that’s got lots of non-starchy vegetables, healthy fats. There’s just really not much comparison we can make there.

And the other thing is that the gut microbiome has really evolved with us, often in the context of periodic ketosis. So if we think about human evolution, we’ve been coevolving with our gut microbiome for thousands of generations. And the environment we evolved in required regular adaptation to changing conditions. When there was nutrient scarcity or even just carbohydrate scarcity, our metabolism would shift to reflect what was available in our environment to consume.

And so we have that metabolic flexibility in our host genome, right. As humans, we have the ability to metabolize carbs or metabolize fats in periods of carbohydrate scarcity. So the real question is why would our bodies not have this…why would our bodies have this metabolic flexibility to deal with the shifting availability of foods and our gut microbiome not also have that same metabolic flexibility and ability to be healthy even when carbohydrates are scarce?

Dr. Hedberg: Interesting. You brought up a really great point about some of these research papers that, you know…the media’s guilty of this and different websites and things like that where they’ll post a kind of really catchy tagline about this diet does this and this diet does that and it’s just focusing on one variable like fat, but they fail to discuss all the other factors in the diet of those individuals. Like you said, what is the quality of the carbohydrates, the fat, the protein, the sugar intake and then everything else in someone’s life? You know, how much are they exercising? Do they smoke? Do they drink alcohol? And things like that. Do you see any good science out there where they take those considerations into account?

Dr. Mailing: Yeah, definitely. There have been quite a few studies actually now on ketogenic diet and how it impacts the human gut microbiome where they’re using a relatively healthy ketogenic diet and generally controlling for all those other variables or at least including them in their analyses. And so for example, in 2014, there was a study by Dr. Peter Turnbaugh’s group at UCSF where they essentially put healthy human volunteers on a short-term plant-based diet or an animal-based ketogenic diet. You know, just for five days but they found that there were distinct gut microbial communities that emerged within as little as three days.

So there was a distinct shift with the animal-based ketogenic diet. And not necessarily one that was, you know, any more pathogenic. There was some increase in hydrogen sulfide producers, which we can talk about a little more later if you want. So in some cases, there might be certain gut microbial patterns that might be…you know, certain overgrowths that might be exacerbated on a ketogenic diet for the average person going on a ketogenic diet, I don’t think we have any real evidence to suggest that that’s gonna be bad for the gut microbiome.

Dr. Hedberg: Excellent. Yeah, that makes sense just because it was…like you said, we evolved with various types of diets and there were certainly sometimes long periods where very low fiber, not much plant food was available and people were only eating meat. We can see certain populations around the world that eat diets like that.

So based on your research and what’s showing now, there…correct me if I’m wrong. So there’s not much evidence that a ketogenic diet is necessarily bad or pathogenic for someone’s gut microbiota other than you mentioned if there’s some level of bacterial overgrowth. Is that correct?

Dr. Mailing: Yeah, specifically hydrogen sulfide overgrowth because there’s certain hydrogen-sulfide-producing organisms like Desulfovibrio and Bilophila wadsworthia being the two most common. Those, if they’re overgrown, they tend to really thrive on animal protein and fat and so if you have an overgrowth of those particular bacteria at baseline and then you go on a ketogenic diet, you’re probably going to exacerbate those overgrowths just because they thrive on those particular types of foods.

Dr. Hedberg: Yeah, that makes sense. So a lot of people…you know, there’s talk about diversity and the importance of that but there’s also, at least from my research, that’s not necessarily all that conclusive either and it seems from my understanding that the real key is reducing inflammation in the gut and if you can reduce inflammation in the gut, then the type of diet isn’t going to have much of a negative effect on the microbiome. What can you say about diversity and where we are as how we look at that and is it really important to have a lot of diversity or are we okay…certain individuals for some periods of time eating a diet that is going to decrease diversity of the gut microbiota?

Dr. Mailing: Yeah, great question. So diversity is definitely tricky to think about. It’s clear that Western populations have significantly reduced diversity compared to much more traditional cultures like the Hadza hunter gatherers, some Nepalese populations that have been studied that are more agrarian. They definitely tend to have higher microbial diversity and that’s also associated with a lack of chronic disease. So we think that this loss of diversity in our essentially industrialized microbiota is potentially contributing to our predisposition to chronic disease.

Now within a western population we tend to see that higher microbial diversity is more associated with health but that’s not always a perfect correlation. I think I’ve seen a few studies. For example, there was one with individuals with major depressive disorder and they found that those individuals actually had higher diversity than healthy controls but it wasn’t necessarily a healthy type of increased diversity.

So diversity does tend to correlate with health but it’s certainly, you know, not the only thing we should be considering when we’re determining, you know, whether we’ve got a healthy microbiome. And honestly, like I mentioned earlier, we’re still really in the early stages of defining a healthy microbiome but I think what you said about inflammation is really key because if we have…you know, there’s many unique states of a healthy microbiome. You know, you and I only share about a third of our gut microbiota and the rest is unique to us. But if we’re both healthy, we should both have, you know, very low inflammation. And so that seems to be a key that is shared across healthy individuals is lower inflammation and a healthy colonic metabolism that actually promotes a healthy microbiota that’s unique to us.

Dr. Hedberg: And just wanna ask you about protein because usually the conversations tend to revolve around fat and carbohydrate and fiber intake. Is there anything interesting out there on protein, you know, high protein, low protein, moderate protein and is there any kind of negative or positive impact on individuals?

Dr. Mailing: Yeah, that’s a great question. I haven’t looked specifically at high or low protein. I know there’s a number of studies that have looked at low protein diets in the context of also having caloric restriction and the effect that that has on the microbiota and that it tends to increase some of the beneficial mucus associated microbes when we get caloric restriction and also protein restriction with that. But I don’t think that that’s, you know, necessarily something we wanna do in the long term and it’s actually the refeeding period where we tend to see a lot of those beneficial changes, interestingly.

So it’s hard to separate out the effects of protein. You know, when you have a lower protein diet, you’re gonna have to have higher fat and higher carbohydrate. You know, one of the two to make up for that, keeping calories equal.

So it’s tricky to tease out the effects of protein. It’s very clear that there are protein-fermenting bacteria in the gut. And so much like fiber fermentation can lead to the production of short chain fatty acids, actually there’s different short chain fatty acids that can be produced from the fermentation of protein as well. So a lot of the research to date has really focused on fiber. So I haven’t really seen any studies that kinda isolate that effective protein but that’d be really interesting to look into.

Dr. Hedberg: Yeah, one of the things I’ve seen clinically is insufficient protein intake and significant gut dysfunction, especially in athletes. And it’s my understanding that the body will cannibalize amino acids from the gut lining if there is insufficient protein in the diet. It’ll mainly draw from the gut barrier, liver, detox enzymes and the skin and then, of course, from muscle. And it’ll break down those four areas if there’s not enough protein in the diet. I just wanted to mention that as an aside. I’ve had a few cases really turn around as far as their gut health. Just getting their protein up to sufficient levels for their given activity level.

Dr. Mailing: Yeah, that’s really interesting. And I certainly think, you know, we don’t know a lot about the effects of various amounts of protein on the gut microbes themselves but it’s very clear that the gut barrier requires protein in order to be able to renew itself. So I think I’ve definitely seen that too in working with clients is that you need, you know, a baseline level of bioavailable protein to be able to heal that gut barrier.

Dr. Hedberg: And what about plant-based diets and why don’t we kind of just tie in low fat into that category? So there’s vegan, there’s vegetarian and it’s my understanding that plant-based diets tend to favor more diversity. What are some of the positives and are there any potential negatives to completely plant-based diet on the gut microbiota?

Dr. Mailing: Yeah. So we definitely see that vegans and vegetarians often tend to eat a lot more fiber. You know, if they’re eating a healthy vegetarian or vegan diet, they do tend to be getting a lot of plant diversity and we definitely think of that as something that is generally beneficial for the gut microbiota. I would say, in terms of specific types of profiles we see in the microbiota that might respond really well to a more plant-based lower-fat diet, that’s actually those people who have the hydrogen sulfide overgrowth where they have that overgrowth of Bilophila wadsworthia. We often see them really improve by shifting more towards a heavy plant-based diet for a short period of time.

Now I do with that have concerns largely around bioavailable protein and getting the nutrients that you need for healing the gut. A lot of the B vitamins are really bioavailable in animal foods. So even in individuals with a hydrogen sulfide overgrowth, I’m not recommending that as a permanent shift. You know, the idea is to hopefully be able to address that overgrowth. The plant-based diet may provide some relief in the short term but typically, I’m hoping to get people back to at least some consumption of animal foods just because I think we can optimize nutrient status best as omnivores.

Dr. Hedberg: Yeah, that’s definitely a hot topic right now, plant based versus…including some animal protein. So you mentioned hydrogen sulfide a few times so far. So it’s my understanding, correct me if I’m wrong, but currently there aren’t any great tests for that. We’re pretty good at doing SIBO breath tests and things like that but no great testing yet available for hydrogen sulfides. We kinda have to go by symptoms. Is there anything new in that on the horizon with hydrogen sulfide as far as diagnosis or are we still just looking at symptoms?

Dr. Mailing: Yeah, it’s primarily looking at symptoms but we can often see an overgrowth of those two microbes that I mentioned or a few others on a comprehensive stool profile. So that’s one other way to look at it. And if there’s hydrogen sulfide overgrowth in the small intestine, that may not show up on a stool test but typically what I’ve seen is when people have those classic hydrogen sulfide symptoms, they’re also gonna show hydrogen sulfide overgrowth on stool test.

Dr. Hedberg: Yeah. Yeah, I have seen that on the DNA, the PCR stool testing. So let’s stay on the theme of diet. You wrote a great article on gluten and gut dysbiosis. So this is probably…our guests can be a little bit difficult to differentiate. Is it the inflammation that the gluten is causing in the gut that’s causing the problem? Is it the wheat or the rye or the barley or the other foods that have it that are causing the issues? What can you tell us about how gluten is affecting gut dysbiosis?

Dr. Mailing: Yeah, so there’s a lot of things in wheat that could potentially trigger symptoms for people who have what we call nonceliac gluten or wheat sensitivity. And because of this, you know, because there seem to be many different triggers in wheat, it’s led to a lot of doubt among the scientific and medical community that gluten is the true cause of symptoms in these individuals.

So for example, wheat is very high in FODMAPs. So these carbohydrates are rapidly fermentable in the gut and for many individuals they can cause bloating gas and other unpleasant GI symptoms. So some studies have found that FODMAP seem to be more of an issue in wheat. There’s also amylase trypsin inhibitors, which are proteins in plants that kinda support the natural defense of the plant against predators and pests. And they can really activate the immune system and cause inflammation. So that’s another potential trigger in wheat.

And there’s also wheat germ agglutinin, which is a lectin. So people who are particularly sensitive to lectins can often get triggered by that. And then there have been studies that have shown that gluten itself is a trigger in some people. So, and then there’s other wheat proteins as well, it’s not just gluten. There is, you know, gliadins, deamidated gliadins, glutenins, gluteomorphin. So there’s a number of things in wheat that really make it tricky to, you know, determine…for the scientific community to say, “This is a real thing.” But it’s very clear that even though there might be, you know, different subsets of people who are reacting to different parts of the wheat, there definitely is, you know, an issue there that’s causing inflammation.

So there are a subset of people with IBS who are responding very negatively to something in wheat and would do well to cut it out for a time. Now whether that needs to be forever? I’m not dogmatic about that. I think there are…it’s clear that there are a lot of people that when they address gut health and really improve their symptoms, they’re able to reintroduce gluten in moderation or wheat in moderation. So I think there is a strong evidence for a connection between gut dysbiosis and an inability to tolerate wheat.

Dr. Hedberg: Yeah, I remember reading a study. I think it was about 10 years ago, maybe longer. It was a study done in Italy on sourdough and people with celiac disease and it was a particular type of sourdough with some different grains in it. But the people with the celiac disease all, everyone in the study, had no negative effects from this particular bread that was prepared the way it was. And so I wonder if…I mean, that’s another thing that I think would be interesting to look at is how the grains are prepared.

And I’ve just had a lot of patients, talked to a lot of people over the years, who, they can do a small amount of sourdough and be fine, but if they go outside that realm, if it’s not sourdough, then they get triggered. And I wonder if that could also be connected to the FODMAP properties if those are altered by the sourdough process. Do you have anything to add to that?

Dr. Mailing: Yeah, that’s a good question as to whether the FODMAP are significantly altered. I know that, you know, sourdough has…the fermentation process reduces the level of antinutrients like the lectins, the phytates and many of the most immunogenic proteins. So basically, the culture that they ferment it with starts breaking down some of these things that are typically…cause a reaction in the gut. I don’t know about the FODMAP though. That’s really interesting. I’m not sure if anyone has looked at that.

But there’s definitely evidence that some of our small intestinal microbiome actually can also influence the breakdown of those antinutrients like the lectins and phytates and some of those immunogenic proteins. And so if we have an altered small intestinal microbiome, then we’re not breaking those down into smaller components that, you know, aren’t gonna trigger inflammation by the immune system.

Dr. Hedberg: Right, right. I wanted to mention one other type of diet that I didn’t mention earlier which was the autoimmune paleo diet. A lot of my listeners are very familiar with that and practitioners as well. So obviously, the AIP diet is going to be anti-inflammatory. It’s just going to be inherently low FODMAP for the most part, depending on the types of vegetables that the individual is consuming on that diet. Anything interesting about the autoimmune paleo diet and the gut microbiota?

Dr. Mailing: Yeah, that’s one of my favorite questions actually. It was actually the autoimmune protocol that helped me to completely clear my eczema. And so I have a lot of personal experience in it and I wondered the same thing when I started studying the microbiome was, you know, did this AIP diet help me because it was improving my gut health.

And there have been quite a few studies with autoimmune protocol now. One showing that AIP was extremely effective for inflammatory bowel disease. I think that was published back in 2017. And then, most recently, I actually teamed up with some of the same researchers that were involved in that study, Angie Alt and Rob Abbott and we did an AIP study for eczema and psoriasis and we did that. We ran the participants through the intervention last fall and we also collected fecal samples and we did a gut barrier permeability test. So we are currently analyzing all the data from that and we’ll hopefully have that to share really soon. So we’ll finally know how AIP impacts the gut microbiome.

Dr. Hedberg: Oh, that’s really exciting. Yeah. Yeah, I remember Dr. Abbott’s study on…I think it was AIP and autoimmune thyroid disease. So that’ll be great. Very interesting. Do you have any idea when that might be coming out?

Dr. Mailing: We were a little backed up in the lab because of COVID. So I’m hoping this fall we’ll be able to have a manuscript that I’ll publish.

Dr. Hedberg: Oh, excellent. So another dietary component that has been talked about a lot recently is resistant starch and how that affects the gut microbiota. A lot of people don’t know what that is. Can you tell us what that is, what foods it may be found in and how it could help the microbiota?

Dr. Mailing: Sure. So resistant starch is essentially a type of starch that passes through the GI tract unchanged. So it’s resistant to digestion by us, the host. And so it basically passes through the small intestine unencumbered by our small intestinal digestive enzymes and it reaches the colon where it can then be fermented by a specific bacterium into short chain fatty acids like butyrate and other metabolites as well. So it’s a type of prebiotic fiber and it also has the potential to selectively promote the growth of certain bacteria in the colon.

And there are four primary types of resistant starch. The first is type one or RS1 is found in whole or partially intact grains, seeds and legumes. RS2 is found in raw potatoes, green unripe bananas, raw plantains. That’s also the most common supplemental form of resistant starch. It’s commonly available as potato starch or green banana flour. And then RS3 is formed when starchy foods like potatoes or rice are cooked and then cooled. So that turns some of the previous digestible starches into resistant starch. And then type four is synthetic man-made resistant starch. It’s produced by chemical modification. That’s like high maize resistant starch that would be added to…it’s commonly added to processed foods but it’s also been studied as like an isolated supplement.

So those four things kind of complicate things when you’re looking at the research. So a lot of people tend to lump all of those into one to, you know, to see, you know, does resistant starch have benefits on our health. But I think it’s really important that we look at them separately because they are very different in their structure and their effects.

So for example, resistant starch in general tends to be beneficial for gut health in terms of increased butyrate production, increased abundance of butyrate-producing bacteria but it’s very individual in terms of the responses. And it’s also dependent on which type of resistant starch. So I have now reviewed a number of studies that suggest that we should really be cautious with RS2 and that’s actually the most common supplemental form. So that’s the raw potato starch and that’s because it’s been shown in several studies to potentially cause gut inflammation. And potentially also then increase the prevalence of opportunistic pathogens in the gut.

So I’m looking forward to seeing more studies. A lot of the studies to date with resistant starch have actually looked at metabolic health markers. So they’ve, you know, they’ve said, “Resistant starch is beneficial because it’s, you know, it’s improving glucose sensitivity, reducing cholesterol, causing satiety.” But I think we need more studies that are looking at gut inflammation and gut barrier function because I think it’s potentially causing some stress there.

The other type that’s commonly consumed is resistant starch three or RS3. And that’s so much more like evolutionarily familiar type of resistant starch. So it’s produced from the cooking and cooling of foods. So when we go back to kinda thinking about the fact that our microbes have coevolved with us, you know, we’ve been cooking tubers and, you know, and eating cooked and cooled tubers for a very long time. So I think that type of resistant starch can be quite helpful and is likely improving the health of the gut microbiota.

Dr. Hedberg: Yeah, resistant starch is something that I’ve…and you may have a different opinion on this but it’s something I wouldn’t use in the beginning. It’s always been something that I would use, you know, the soonest would be maybe a few months in, two or three months of a gut healing program. I’ve just found that doing things like that, any kind of prebiotic or something like resistant starch is just, it’s not a good idea in the beginning. Have you found that as well or have you used it right away in patients and gotten good results?

Dr. Mailing: Oh, absolutely I wait to introduce any prebiotics but particularly resistant starch. And I would never introduce it as a supplement. So if the person can tolerate whole foods sources of resistant starch, then they can slowly start to incorporate those. But typically, with someone who’s got some significant gut healing to do, they can’t tolerate any types of fiber. So if they can’t tolerate whole food sources of fiber, I’m not gonna be, you know, suggesting that they down some raw potato starch just to, you know, just to try to get fiber in there because it’s more likely to cause inflammation when, you know, when you’re not tolerating fiber. And inflammation is just going to lead to a more dysbiotic gut in general.

Dr. Hedberg: You mentioned butyrate. So that’s a short chain fatty acid that’s produced when the gut microbes break down the food that we eat. Can you talk a little bit more about butyrate and why that’s beneficial to have more butyrate in the gut?

Dr. Mailing: Sure. So butyrate is the preferred source of energy for the cells in our colon that line the gut and form that gut barrier. So over 60% to 70% of the energy requirements for those gut epithelial cells is coming from butyrate. And so it’s increasing their turnover, it’s increasing the repair and essentially, the tightness of the barrier.

It’s also very immunoregulatory. So it’s reducing inflammation in the gut and kind of regulating the immune system. It also stimulates the secretion of mucus from the gut which is really important for essentially maintaining a little bit of a gap between the epithelial cells and the microbes. Because if the microbes start adhering directly to the epithelial cells, we’re gonna get major inflammation. So that mucus layer is really important and butyrate stimulates the secretion of that mucus.

Dr. Hedberg: And just so the listeners know, are there any strategies, anything they would want to include in their diets, type of eating that would improve their butyrate levels and is there ever a time where you don’t want to increase butyrate?

Dr. Mailing: Yeah, so there’s a number of strategies to increase butyrate. The primary way is to consume fiber since the fermentation of fiber by our gut bacteria is what produces large amounts of butyrate in the gut. So that is the primary way to achieve butyrate levels. And through consuming fiber, there’s really not any way you’re gonna get too much butyrate. We actually probably have lower butyrate levels than our ancestors did since they were consuming much, much higher amounts of fiber and had more diverse gut bacteria. So you’re not gonna achieve too high levels of butyrate through diet alone.

Now you can also supplement with butyrate and that you could definitely overdo. So there’s a lot of like calcium and magnesium butyrate salts out there on the market and you can, essentially, you look at the label and they’re suggesting pretty like megadoses. And part of that reason is because they’re providing like five-gram doses in the hopes that some of it is gonna make its way all the way down to the colon. Right? But it’s also providing basically a super physiological dose of butyrate.

And when the gut is inflamed, too much butyrate could actually…there’s some evidence to suggest that too much butyrate might actually impair the ability of stem cells in the gut to kinda repair the gut barrier. So if you have significant mucosal inflammation going on, low amounts of butyrate could be helpful but kinda megadoses of butyrate like you would get from supplements could potentially be harmful.

So if I do recommend supplementing with butyrate, it’s typically brands that are specifically targeted more to the colon, have a slower release and are of lower dose. So there’s two that I’m aware of. ProButyrate from Tesseract Med is kind of like a fiber matrix encoded butyrate. And then the second is Butycaps which is a tributyrin form. So it’s like bound up in a triglyceride form. It essentially helps it traffic more to the colon before it’s broken down and released.

And then, you know, if the…interesting thing is that there’s also increasing research that beta-hydroxybutyrate, which is a ketone body, could actually fulfill some of the same roles of butyrate in the gut. So if you can’t get butyrate production from fiber, it’s possible that you could get it from ketones from essentially going the other way. From the bloodstream, the gut will pick up ketones and that will feed into the same metabolic pathway as butyrate and help support the gut barrier.

Dr. Hedberg: So would you say that butyrate supplements could be used in an individual who cannot tolerate fiber and they have gut barrier dysfunction? Would that be correct or is that not correct?

Dr. Mailing: Yeah, that is correct. I would just choose those that are a little more targeted to the colon and are lower dose. But definitely, that could be beneficial and I’ve seen a lot of people get major improvements from that. And, you know, also, when you start to tighten up the gut barrier, you start to provide butyrate to be able to bring down inflammation. Often you can then start to tolerate more fiber as well.

So it’s not…it’s definitely not a long-term solution because the amount of butyrate you’re gonna be able to provide via supplements is never going to equate to the amount that you could get in a healthy gut from fiber. So the goal is always to address the overgrowth and/or the dysbiosis and be able to get back to a place where you can tolerate fiber and produce your butyrate that way. But in the short term when we wanna kinda help out the gut barrier that’s starving for energy and is really inflamed, providing some supplemental butyrate can definitely be helpful and that has been demonstrated in several clinical trials, even in cases like ulcerative colitis where there’s, you know, significant inflammation and gut permeability going on.

Dr. Hedberg: Yeah, I wanted to ask you about fiber and what some of your favorites are. So there’s soluble and insoluble. And I’ll usually start with a soluble because it’s not as irritating to the gut lining. So there’s, you know, there’s flax fiber, there’s acacia fiber and then you can move on to things that are highly insoluble like cilium and things like that. So what’s your approach with fiber and what are you using?

Dr. Mailing: Yeah, I have seen that as well that soluble fiber can often be tolerated a little bit sooner than insoluble fiber. I don’t really necessarily make that distinction and I don’t really have a set protocol for implementing fiber largely because a lot of the clients I work with are on the extreme of difficulty with their gut health and so they can only tolerate a few foods and when they’re expanding the…they’re starting to expand their diet to include more foods, it’s often still very limited. So I often let that direct which fibers they are able to incorporate.

And it really does seem to be different for everyone. So while one person might tolerate cilium really well, another person might really not respond to that. So, and the truth is we don’t have the diagnostics, you know. Even if we do a full gut profile, we can’t yet predict how you’re gonna respond to a prebiotic fiber. And it’s often counterintuitive the way people respond sometimes. So I don’t really have a set protocol for that. It’s more really encouraging people to, you know, to listen to their body and see how their symptoms respond to in trying to incorporate various different types of fiber.

Dr. Hedberg: Right, right, yeah. I don’t use much fiber in practice. Usually it’s, you know, once you get the diet right and you get things back in balance as far as dysbiosis and hydrochloric acid and pancreatic sufficiency and things like that, you tend…at least I see I tend not to need to use a fiber supplement and I can get the patient eating enough in their diet. In any case…

Dr. Mailing: Absolutely.

Dr. Hedberg: Yeah. So you wrote an interesting article on vitamins and minerals for gut health. Can you walk us through some of the most important vitamins and minerals people should know about for healthy gut function?

Dr. Mailing: Sure. So maybe we can start with zinc since we’ve been talking about the gut barrier. So zinc is really important for activating a protein called collagenase which essentially allows our cells to remodel collagen during wound healing. And so it’s been shown to reduce gut barrier permeability. So that is definitely very important.

Vitamin D is also really huge to gut health. We see lots of epidemiological study showing a strong association between vitamin D deficiency and increased risk of inflammatory bowel disease. So vitamin D has been shown to be important in maintaining gut barrier function and also in maintaining a healthy balance of bacteria as well. So we see there’s been a few studies looking at vitamin D deficiency and how that impacts the gut and it does tend to increase bacteria that we think of as associated with dysbiosis. So that’s particularly important and hopefully easier for a lot of people now in the middle of summer to be getting enough of that.

And then I’ll also say vitamin C, I see as one that a lot of people are deficient in that is really crucial. Again, related to the synthesis of collagen. Vitamin C is really involved in wound healing so vitamin C would be another that is really important.

Now the truth is we have very few studies that have looked at the supplementation of isolated micronutrients and how that impacts the gut microbiota and gut barrier function, particularly, how it affects the gut microbiota. So there are some nutrients that have been shown to be really detrimental in supplementation. Iron being one of them. So iron particularly tends to be important for opportunistic pathogens in the gut and for example, they’ve done studies in malnourished children trying to supplement iron to improve their iron status. They found that it causes massive dysbiosis in the gut. So we do wanna be careful with providing supplemental nutrients in significant amounts, you know, especially if they’re not needed. So definitely would be worth, you know, getting some nutrient testing to see if these are worthwhile before blindly, you know, just throwing vitamins and minerals in your gut.

Dr. Hedberg: That’s right. Right. Yeah, with iron, if the ferritin is extremely low, the patient isn’t usually going to be feeling very well but you also don’t want to create more issues in the gut by supplementing with iron too soon. And the ferritin’s usually low because of gut dysfunction in the first place. So there’s a lot to look at there from that perspective. So interesting. So yeah. A lot of those, like zinc, vitamin D, C, these are just kinda some of the classics that you would recommend to someone trying to prevent a cold or a flu and strengthening the immune system. And that makes sense because most of the immune system is in the gut. So interesting.

Now you wrote a really great paper on exercise and so the title of the paper is Exercise and the Gut Microbiome: A Review of the Evidence, Potential Mechanisms, and Implications for Human Health. And this was published in “Exercise and Sport Sciences Review.” So can you kinda summarize for us what you found, how exercise impacts the gut microbiota?

Dr. Mailing: Yeah. It’s a big question. This has been a really exciting area of research in the last 10 years and one that I got involved in when I started my PhD research at the University of Illinois in Dr. Jeff Wood’s lab. And when I joined the lab, they had essentially just recently done some studies. They were using a colitis model and trying to see if exercise could be beneficial for ameliorating colitis. And what was really interesting is they found that voluntary wheel running, so when they allowed mice to run on a wheel as much as they wanted during the day, that was protective against colitis. But when they forced the mice to run on a treadmill, it exacerbated colitis and increased mortality.

So that was a really interesting finding and, you know, they were trying to figure out, well, what is the mechanism for this, what is going on that’s causing these disparate outcomes in colitis. And so then there was a new student that joined the lab, Jacob Allen. And he proposed that, you know, maybe the gut microbiome is involved and he started looking into that and he found, lo and behold, the two different types of exercise cause very distinct shifts in the gut microbiome. And so that’s how our lab kinda transitioned from an immunology lab primarily into a real focus on how exercise impacts the gut microbiome.

And we certainly weren’t the first to show that exercise impacted the gut. There had been other animal studies that had shown that exercise was able to alter the structure and function of the gut microbiome. We’d also seen there were a number of cross-sectional studies that had been published where they essentially took a group of athletes and a group of sedentary people and just profiled their gut microbiota and kinda looked at what differences there were. And there did seem to be, you know, increased diversity in the athletes’ microbiome, increased short chain fatty acid production and turnover of carbohydrates in the athletes but athletes also tend to eat very differently than nonathletes. And so when the researchers controlled for the effects of diet, a lot of those associations fell away. So it was still unknown as to whether exercise training could actually, independently of diet, impact the human microbiome.

And so when I joined the lab, I partnered up with Jacob Allen and we ran the first longitudinal study of exercise training on the human gut microbiome. So we had 32 individuals. We had a lean and an obese group but they were otherwise healthy, no active GI conditions or anything like that. And we found that six weeks of exercise training in these previously sedentary people had significant changes in the gut microbiome. And then when they reverted and went back to their sedentary lifestyle for another six weeks, a lot of those changes in the microbiome disappeared.

So we definitely thought, you know, this is really showing there’s a real effect of exercise here and, you know, and a lot of the changes did seem to be beneficial. We saw an increase in butyrate producing bacteria, particularly in the lean individuals. And so that has, you know, a lot of wide-ranging applications not only for gut health but we also know that small amounts of butyrate can get into circulation and have effects on the brain, on muscle, on insulin sensitivity. So this was basically suggesting that some of the effects of exercise, you know, might be mediated through beneficial changes in the gut bacteria.

Dr. Hedberg: Interesting. So why don’t we close with a question on probiotics and antibiotics. There were a few papers recently published that shed some doubt on using probiotics after someone has taken antibiotics and it was my understanding that these kind of hinted that perhaps they can delay the restoration of the gut microbiota back to the state it was before the antibiotics. So they could be detrimental but there’s also I think a lot of holes in some of these studies. So what’s your opinion on what’s come out on that question and the studies on probiotics after antibiotics?

Dr. Mailing: Yeah. So I should start by saying I’d love to see a lot more research in this area because I think it’s definitely needed. But there was this one very comprehensive study that was published in late 2018 by Eran Segal and Eran Elinav at the Weizmann Institute of Science and they essentially had three groups of people who they gave antibiotics. And then the first group was allowed to just recover over time with no intervention. The second group was given a probiotic and then the third group was given an autologous fecal transplant. So this meant they stored some of their stool before antibiotics and then they reinoculated them after the antibiotics.

And they found that the spontaneous recovery group took about three weeks before their gut microbiome looked close to normal. Obviously, we know that antibiotics can have some long-term effects. So, you know, it wasn’t necessarily completely as it was before but after 21 days, it was close to normal. The probiotic group took between three to five months to restore their gut microbiota indicating that the probiotics were actually delaying the return of the native ecosystem. And then the autologous fecal transplant group had a near complete restoration in less than a single day which was really quite amazing.

But focusing back in on the probiotic group, I think it’s very easy to think of the gut as a simplified system and to say, “Well, we’re clearing out the gut with antibiotics. So why not throw some of these beneficial microbes in?” And, you know, think we’re repairing it. But the truth is that most probiotics are made of Lactobacillus, Bifidobacterium strains and those actually only make up about, you know, a maximum of 3%, maybe 5% of a healthy gut. But typically, much lower than that.

So we’re essentially putting in massive amounts of these probiotics and allowing them to colonize the ecosystem. And, you know, there’s many native microbes that we can’t give as probiotics like the butyrate producers who might be outcompeted by those probiotics when we put them in there in high doses. And so it’s essentially, you know…maybe we’re preventing some chance of infection. You know, there’s some evidence to suggest that probiotics during or after antibiotics might reduce the risk of C.diff infection but it’s coming at a cost because we’re delaying the return of the native ecosystem and essentially almost creating like a monoculture of these probiotic strains that seem to be taking over and kind of delaying the return of those butyrate producers.

So I’ve really spoken up about this because I think there’s just…you know, it’s no hesitation. Even many conventional doctors now are prescribing probiotics every time you get antibiotics and we just don’t know enough to know whether that’s actually beneficial. Maybe we’re actually increasing someone’s risk of infection for five months instead of, you know, an acute period.

So it really depends on a lot of factors and there might be some cases where that might be beneficial if you have someone who’s, you know, really like potentially immunocompromised or in a hospitalized situation where they’re very likely to contract C. diff. Then the benefits of taking some probiotics after antibiotics might outweigh the cost of returning the…delaying the return of the ecosystem. But yeah. And there’s actually some really interesting research around butyrate and its potential to be a much better option for supplementing with butyrate during antibiotics. It may actually support the gut barrier and support the return of beneficial bacteria inhibiting the expansion of pathogens that often occurs after antibiotics.

Dr. Hedberg: Interesting. And again, so the butyrate supplementation, you had mentioned a dose of five grams. Was that correct?

Dr. Mailing: Well, so five grams is typically the megadoses given of like calcium or magnesium butyrate salt. So I think that’s probably much too high even for someone who’s on antibiotics where their butyrate producers are being wiped out. I would typically…most of the targeted butyrate supplements are providing more of like 300 milligrams dose of butyrate per capsule. And when you went on antibiotics, I think you could take, you know, a larger amount of those capsules. I’d really like to see some clinical trials because I don’t like making that recommendation without really knowing what dose we should be providing during antibiotics and I hope we get some research to shed some light on that soon.

Dr. Hedberg: And so assuming that those papers were accurate regarding antibiotics and probiotics, do you have a sense of how long one should wait to take probiotics after antibiotics or is that just a real unknown at this point?

Dr. Mailing: That’s a very good question. And one that we don’t necessarily know based on evidence where they’ve waited and then introduced probiotics but we do know that that spontaneous recovery group, often around three weeks post antibiotics, your gut bacteria, your gut microbiome is looking more like it did before antibiotics. So the bacterial load is returned and, you know, your butyrate producers have had a chance to recover. So when I’ve been asked this in the past, I’ve typically said, you know, “Probably around the three-week mark is when it’d be, you know…introducing probiotics isn’t going to necessarily take over that open niche because the bacteria and other microbes have largely returned.”

Dr. Hedberg: Excellent. Well, this has been really fantastic. Thank you for coming on. It’s been a real treat having someone with a PhD focused on the microbiome and…

Dr. Mailing: Yeah, thank you so much for having me.

Dr. Hedberg: And so, Dr. Mailing, how would you like people to find you? What is your website and what’s the best way to reach you?

Dr. Mailing: Yeah, lucymailing.com is my website. I’ve got lots of free content there about pretty much all the topics we covered today. You can also find me on social media @lucymailingphd. Although I’m not nearly as active as I am on my blog. So my website is definitely the best place to get in touch with me.

Dr. Hedberg: And that’s lucymailing.com, correct?

Dr. Mailing: Yep.

Dr. Hedberg: Excellent. All right, well, thanks for tuning in, everyone. If you’d like to read a transcript of this interview, go to drhedberg.com and I’ll have links to Dr. Mailing’s website where you can read her articles. And Dr. Mailing, you also do telehealth consultations. Is that correct?

Dr. Mailing: Yeah. I do.

Dr. Hedberg: Okay, excellent. So you can contact her that way if you’re interested in that as well. Well, thanks for tuning in, everyone. Take care. This is Dr. Hedberg and I will talk to you next time.