From Disruption to Recovery: Understanding Antibiotic Impact on Your Gut

Foreign.

Hello, everyone.

Welcome.

Thank you so much for joining us today for our webinar on understanding antibiotic impact on the gut. So it's a very exciting topic we have today and lots of interest. You know, many people have taken antibiotics over the course of their lifetime, and so it is a topic that, you know, is applicable to almost everyone. So my name is Chalice. I'm a dietitian, and I am the clinical success manager here at Tiny Health. So my role is really to help support our practitioners who utilize our tests and how to, you know, plan out support for their patients. And so that is a lot of what I do. Building out resources, doing webinars like this with our awesome science lead, Kim. And so, Kim, would you like to introduce yourself?

Yeah, happy to. I'm Kim Sukum. I'm the head of science here at Tiny Health. I've been with Tiny Health basically since the founding. Really helped kick the science team off. And really the goal of the science team and the goal of what we've been building for the past four years is really to have a, a comprehensive gut microbiome report. So everything from metric creation to interpretation to better understanding the mechanisms and methods and functions that your gut microbiome does and what does it mean and how it connects for your health. So that's the big, the big goal of the science team, what we've been working towards. Before this, I worked at Washington University in St. Louis, and my, my research really centered around actually antibiotic resistance, which makes this topic very relevant and very, very interesting to me from, from that whole perspective. I worked on everything from, from infants in the NICU who had multiple doses of antibiotics really at the beginning of life, all the way to, to Alzheimer's and HIV individuals who'd spent, you know, had decades of different types of medications impacting their gut microbiome and what their antibiotic resistance looks like. So full spectrum of health and life and really, you know, really brought that all to Tiny Health and are really kind of reflecting on that today, too, as we think about antibiotics and their, their lifelong impacts.

Thank you, Kim.

Awesome. Let's. Let's dive in then. So a little bit of an overview first. We're going to start with how antibiotics disrupt the gut microbes and what they're doing and how they interact with your system in general. And then we'll, we'll follow up and talk about ways you can help your microbiome bounce back and recover faster, thinking about really practical steps to think about antibiotic recovery. And we'll end with Some real case studies that show the impact of antibiotics on the gut health and possible steps and impacts of different, different actions to help speed up that recovery. So really, the full scale of antibiotics and gut recovery. Awesome. Let's start with a little bit about antibiotics in general. Antibiotics have really revolutionized medicine, especially in the past hundred years. They've made a lot of things possible that weren't, and they've saved millions of lives, probably with the ability to fight infectious diseases. However, this means the flip side of this is that we use a lot of antibiotics and a lot of people interact with them on a yearly basis. And the tools of that, and what that means for our microbial community is something that is often not examined in a really thorough manner. And so we're first, we're going to start out with antibiotic usage in general. And we actually have a little poll for you to take that should pop up right now. Please feel free to submit an answer. Have you had a course of antibiotics this year for any reason? A lot of you will probably be thinking specifically about oral antibiotics that you take, but there are different types of antibiotics. Eye drops, ear drops, all of these work. We're considering, as we think about antibiotic usage in general. Looks like we're seeing 30% yes and 6 plus 60% on the no. Yeah. So generally a pretty healthy population. It sounds like not very much use for antibiotics. And this is actually probably a deviation from, from nation averages. Across the US over 230 million oral antibiotic prescriptions are given out every year, which results in most adults having at least one antibiotic course in a given year. So seven out of 10 adults, something around there which is a lot of antibiotics and a lot of antibiotic usages. And these numbers are generally going up worldwide. So here we're looking at daily defined dosages, and these are in the billions. And you can see where we currently sit, and this was a little bit old, but you can see where we're currently around 50 or so daily dosages of antibiotics. And these are just projected to double and increase until 2030. And this is varied depending on country and location, but the general pattern is very clear. Antibiotic usage is highly, highly common and just getting more and more common. And, and this has potentially big impacts on what's going on with the gut microbiome. And I think the really important thing too, when we think about all these antibiotics and all these antibiotics that everyone is taking, is that often antibiotics are taken for poor reasons or they are. They are unnecessary. Many antibiotics are given out for viral Illnesses, these are things like colds, flus, sore throat, ear infections. If the illness is caused by a virus, antibiotics will not help that illness. It's not going to get rid of the viral infection. And, and so in this case, the antibiotic was unnecessary. And CDC reports this at at least 28%. So roughly 30% of these fall into that category of unnecessary antibiotics. And why, why are these given out in general? Often it's, it's thought of as a just in case. So someone comes in with a certain set of symptoms, maybe they take a culture that, that's sent off to the lab to get an idea of what exactly is causing it. But often antibiotics are prescribed without that culture, without that idea that it's bacterial infection, just in case this would help with it. Often antibiotics are also used in very low risk situations prophylactically. So with the idea that this will help prevent an infection before an infection occurs, because you have a potential lower situation. So both of these are potential cases where the antibiotics weren't necessary, but were given out anyway, and increasing those courses nationwide. Also, for even cases where antibiotics are necessary, where a bacterial infection has occurred in about 50% of outpatient settings, the drug choice, dose or duration is inappropriate. So again, often antibiotics are very specific to what particular bacteria is there and its resistance to different potential antibiotics. And again, this is a very complicated thing for doctors to figure out. Often you have to have cultured or done some kind of workup to figure out what bacteria is there, what dosage appropriate. Often you don't see this changing even when the culture work comes back. So even in these cases where antibiotics are necessary, often potentially multiple rounds are needed because the wrong antibiotic was used. So all this results in a picture of a lot of antibiotics. And this is important because it has a big impact on your microbial ecosystem that lives in your gut. So our bodies are not just those bad bacteria that are causing infections, but the good ones too. And these are just as impacted by antibiotics as, as your infectious ones. So first off, okay, you take that antibiotics, you get that dose for say, a sinus infection or whatever. The reason that you have to take antibiotics, what is going on with those antibiotics and how, how are they affecting the rest of your system? When do they actually interact with the gut microbiome? Most antibiotics are systemically absorbed. So we're hoping that they get into the bloodstream and circulate and this is how they will, they will get to the problem and they will take care of that bacterial infection. And the antibiotics that are orally Given these, these pills that you take often directly contact that gut bacteria during digestion. Right. So the, the capsules are breaking up, you're absorbing the antibiotic. Small traces of it will also of course, make it all the way down through to the large intestine where you have this live ecosystem of bacteria existing and will have an impact there. Even ones that don't directly aren't taking orally and don't directly go into your gut often make their way there through being recycled through the liver. So even if you're not necessarily taking an oral antibiotic, that doesn't mean you're not having an impact on your gut microbiome, even targeted antibiotics. So this varies. There's a lot of different types of antibiotics and depending on what type of antibiotic, you're going to see different impacts. But even targeted antibiotics that are going after particular types of things and infections often reach the gut in detectable concentrations. So we're often not even avoiding it in those cases where we're trying to get something very specific. And up to 70 to 80% of antibiotic classes will affect the intestinal microbiome. So while you're taking that oral microbiome or that oral antibiotic, and it is doing great things to kind of help clear the infection in the cases where you have a bacterial infection, otherwise you still have this rich community of gut microbes that are also going to be impacted as these antibiotics go through. Awesome. Let's do, let's do another poll and talk a little bit about common short term effects. What have you guys experienced? What if the answer is other, feel free to put it in the chat too. What else you could be experiencing or if you just didn't experience any side effects. So there are a lot of different side effects of the antibiotics and I think there's a lot of different reasons why we might be experiencing the different side effects. A lot of these side effects are very gut focused and often come into play when we think of what's happening to the gut microbiome. So when we talk about these antibiotics and kind of wiping out this community, we're also going to kind of keep tying it back to what you might be experiencing. When this happens. Often those bacteria are kind of silent, living in your gut, silent in that it impacts your digestion, it impacts your daily life, but it's an invisible force that's happening when you take antibiotics. You've put a massive clear out of that invisible force. And so seeing these side effects, seeing kind of the negative impacts are not uncommon and it's really often variable, depending on what your community looked like and how it reacts to the different antibiotics, but very common ones. Let's see, what were the common responses in the poll? Did you see.

Looks like stool.

Very common.

Abdominal discomfort for sure.

Yeah. Indigestion, bloating. I think the loss of appetite was an interesting one for me. That came up as I was looking through kind of common ones. I've never experienced that one, but apparently it comes up not infrequently as you're taking antibiotics. Rash. I know that's my. My daughter, when she has to take antibiotics, develops a rash, which is concerning. Yeah. So a lot of common side effects and often this happens while you're actively taking it and even can linger on even after you've finished your antibiotic dose in course. So what's going on in the ecosystem here? Antibiotics are specifically targeted, are supposed to be working on the pathogens. Right. You have an infection, you have an overgrowth of a particular bacteria which is causing an issue and causing an illness. And the goal is for those antibiotics to wipe that out. However, antibiotics are not specific, often for just that infection, and they can wipe out your beneficial species. Also, a lot of the beneficial bacteria in your gut look very similar to things that can cause infections. So even when they have high specificity, it often has side effects of hitting these beneficial microbes that are living in your gut and doing positive things in general for you. And if the microbiome is considered to be an ecosystem, this thriving system, then antibiotics can be seen as a forest fire. They run through some things, manage to hide from it. Some things are very good at kind of getting out of the way of antibiotics often. Again, we're looking right now at a picture of your mucous membrane lining here inside your gut. Some things manage to curl up and hide in there as antibiotics go through and aren't as impacted. And a lot of things are just kind of wiped out as it comes through. And often, like if you think of it as a forest fire, after a forest fire goes through, you're working on this, replenishing that ecosystem again and getting to a state where you have a healthy ecosystem and it takes a while and what kind of comes through. And the first things that succeed are not often the best things for your gut. And I really want to emphasize this because I think everyone sees antibiotics as. As like, you know, like they all have really complex names too, which doesn't help the issue. So when you're prescribed an antibiotic, sometimes you have a very clear idea of okay, this is a really narrow spectrum going to go after this particular bacteria, but a lot of them are very general. And your impact to the gut microbiome really, really varies by the spectrum, dose and duration. And as we talked about kind of earlier, often those should be prescribed and are really supposed to be targeting a particular type of infection. But if it's a very broad spectrum, it's unclear what's happening. Often you get something that can wipe out large masses of your gut microbiome as well. So let's talk about a little bit more specifically, what's happening as these antibiotics are coming in and what are kind of the measurements. I mean, at Tiny Health, we always come down to. We want to measure what's there, we want to understand with metrics so we can understand how best to support when these kind of things happen. So when antibiotics come in, we talk about it first, kind of the phase one. Phase one is during the antibiotics where it's coming through and wiping out, you know, pretty much indiscriminately. We often see a drop in alpha diversity. Alpha diversity is how we measure how many different type of species there are and their balance. So if you have a lot. So typically in an adult, healthy adult gut, you have a lot of diversity. You have a lot of different types, a lot of different species all doing different functions, and they're relatively evenly distributed. After antibiotics come through, we see a drop in these species. There's fewer and fewer species, often there's ones that dominate, so you'll end up with a lot higher abundance of one than another. And the alpha diversity goes to. Goes way low. And alongside this, you often have this drop in beneficial commensals. So things like Bifidobacterium bacteroides, picolobacterium, these are things that don't often have a lot of antibiotic resistance. So when we think of what's in your gut, our commensals are not necessarily well equipped to survive antibiotics. So when they come through, often these beneficial taxa are the first that kind of get wiped down and see that drop in diversity. And then after we see that overall drop in diversity, we start to see phase two happening, which is things start coming back. And of course, when things come back, when you think of a forest fire, what comes back isn't the healthy oak trees that you'd want. What comes back initially are weeds, are things that are fast growers, are opportunists, and are really, you know, like, they take advantage of that environment that's now kind of wiped out to really kind of thrive. And these are often things that we think of as associated with potential opportunistic pathogens or inflammation in the adult gut. So things like Enterobacteraceae, Enterococcus C. Diff. These are things that take advantage of that wiped out ecosystem to kind of start, start really kind of increasing in length. These are often osp. So the culprits in some of those symptoms we discussed earlier, things like diarrhea or yeast infection, is because you might have a candida growth after you've wiped out all the beneficials. And these are the things that are now left to kind of come into this space. Here's a little bit of a real life example of impacts that happened. This is in a breastfeeding infant. And so here's our metrics over time. We're looking at Bifidobacterium that was in that first category of commensals, especially at this age. At this age we want Bifidobacterium to dominate the gut microbiome of the baby. This is one of those that's more susceptible to those antibiotics as they come through. And here's Enterobacteraceae. Enter Bacteraceae is one of those, on the other side of the equation, that opportunist that wants to kind of invade but is kept low by Bifidobacterium. So breastfeeding infants needed two courses of antibiotics for ear infections during three months of life. So really early on, and you can see like Bifidobacterium had been rising since birth, a little bit low to begin with, but then had been going up nicely and then a little bit down. But then after antibiotics, two course of antibiotics, we see this sharp decrease between three months and four months where it's basically wiped out of the gut. And Bifidobacterium is one of those that's really good at changing the environment to help keep pathogens and opportunistic pathogens out. So once that drops down, we see this massive spike in Enterobacteraceae coming up alongside it. So really, really easy to see the big impacts that antibiotics can have in a relatively short period of time here. Now let's talk a little bit about antibiotic resistance. So antibiotic resistance then is another consequence of antibiotic usage. So if you have a community, so this is like, let's talk about the active infection. We'll, we'll kind of bring the gut microbiome into play here as well. But if you have this harmful community of bacteria that, that's causing an infection and there is A particular mutant in here that has antibiotic resistance. When you take antibiotics, it creates selective pressure. So it's going to wipe out all the non resistant cells here, so all the ones in yellow that is not resistant to bacteria and then that antibiotic resistant one can survive and proliferate. This is also why, especially as you're prescribed antibiotics, it's really stress to take your entire course because stopping halfway through encourages whatever's there that's resistant to continue to thrive and take over that environment and actually encourages greater and greater antibiotic resistance. But this will happen even if you take your potential full course and have something happening that's worldwide with more and more antibiotic usages, where seeing more and more antibiotic resistance evolve. It's a natural kind of reaction to a strong selective pressure which antibiotics currently are. What this means for you across your lifespan then is as you take antibiotics, it's highly possible to get antibiotic resistance living in your gut and have it continue to proliferate as you take more and more dosages over time. The tiny health report looks at this in two different ways. We look at the antibiotic abundance index and the antibiotic richness index. Both of these are measurements of those opportunistic pathogens and the ones that particular carry a lot of antibiotic richness. So here you can look at antibiotics were taken I think right after the 11th month sample and you can see the antibiotic abundance index increase and richness increase as well. Now what's interesting is even after those bacteria leave, you can still see high amounts of antibiotic richness. So. So low levels of things that didn't quite get wiped out of the gut that keep around and may potentially cause issues later in life with other introductions of antibiotics or other infections. And this is something that happens like we think about this in a lot of ways. It's happening in your ecosystem, but it's also happening in the environments that you interact with. It's happening in hospital systems, it's happening across your home. So it's definitely something to always be aware of as we take more and more antibiotics, that it leads to an antibiotic resistance effect. And why is this important? That makes these bacterial infections harder and harder to treat in the future as they are resistant then to that particular antibiotic. Okay, let's go into more. So we talked about short term and we talked about the community collapse and then that increase of those unfriendly opportunistic pathogens. Let's talk about more long term consequences. So after this, again, thinking of the forest Fire. What happens long term of you who have had antibiotics recently, or if you're thinking back in the past, have you ever experienced symptoms from antibiotics that lasted longer than a week? So this is after your antibiotic is gone, after you should be starting to feel normal again. Your community is recovering. Long term impacts. Some have been so far we got a little bit of split, quite a few unsure. I think unsure is really common. Sometimes it's really hard to tell if it was an antibiotic cause or maybe it was something else. Maybe it's still the lingering infection, maybe it's something else that's, that's driving the symptoms that you see. I feel like every time I take antibiotics it's always one of those kind of cringe moments because I'm never entirely sure how long it'll impact me and how long it'll take to get back to normal. So let's talk about what are some of the long term consequences and especially in healthy individuals. And then we can start like talking about what do we do about it. So now we kind of talk about phase three. So we've gone through antibiotics, we've gone through potentially the surge of opportunistic pathogens. Phase three is more of the ecosystem recovery. This is where diversity rebounds, although often it doesn't quite return to baseline. In this study, this was a study I was part of back at Washington University, we gave antibiotics to healthy individuals. These were common antibiotics that are prescribed for respiratory infections, things very commonly given to healthy individuals and then tracked over time what was going on with their microbiome. You'll notice that there's a baseline period, that perturbation, specifically with the antibiotic, where we see the diversity drop. And then we have this long slope of recovery that lasts from weeks to months before we hope to get it back up to what that baseline was. And this period is really what we consider antibiotic scarring, because sometimes this happens quickly and sometimes it's something that can really linger on for long periods. And other studies have shown this too, that while we want this recovery, like, you know, ideally you need antibiotics, you take them and we have a sharp kind of recovery, back to normal. But in some cases, certain keystone taxa like Bifidobacterium or Colibacterium often fail to recolonize and they don't come back in the gut and you have a different composition. And this residual imbalance can persist for months, affecting both your metabolism and immune system outside of this as well. And for some individuals, it's more dramatic than others. I'll Dive a little bit more into that specifically. So some gut microbiomes actually never fully recover. So, so one interesting thing we found in this study, you can see of this population, all the blue individuals were ones who bounced back and got back roughly to baseline. Maybe a few taxa missing, but roughly back to normal. While the pink ones actually ended up, and these were initially healthy individuals actually ended up in a different state entirely. So they ended up looking more like ICU patient microbiomes and they never actually came back to that healthy state. So this is a case of an ecosystem that's thrown off balance. So here you're in a, in a healthy state, you're thrown off balance by antibiotic resistance. And rather than going back to your previously healthy state, you end up in this relatively less healthy gut inflammation state, which then can have lasting impacts and is much harder to get out of, to return back to that healthy microbiome state. Now this was just a small proportion of the population, so this doesn't necessarily happen to everyone. And a lot of this, and we'll talk about this where we talk about recovery as well, a lot of this can depend on what your initial composition looks like. So the stronger your gut microbiome is as you enter into antibiotics, the less likely it's potentially going to be knocked off kilter into a state where it's hard to get back. Let's talk a little bit about. So I know we talk a lot about with adults here, but let's, let's chat a little bit more broadly about antibiotics that have more lifetime impacts and what this means across your lifespan. So we talked about in adults, let's see, maybe it should come up in adults, one of the most common risks, and this was from 2016, so a little bit dated here. So we have even more things here potentially. But one of the most common risks is increased risk of C. Diff infection after antibiotic usage. But there are longer term impacts depending on when you take those antibiotics in your life. And when we look at younger individuals, so anywhere between one year up to 70 years, we see an increased risk of type 2 diabetes associated with repeated antibiotic usage. When we look at this really narrow window of infants under one year, we see an increased risk of childhood obesity with antibiotic usage. And even earlier in this time period, we see an increased risk of infections, asthma, allergies and type 1 diabetes. And across this entire time span we showed what I just showed with this increased risk of loss of microbial diversity and enrichment for resistance genes. So long term impacts are highly variable. But Often antibiotics at any time can have long term impacts. And especially when you take antibiotics very early on in life, the risk of having even longer chronic conditions grows up with antibiotics. While there's a lot of hypotheses for what could be driving this, a lot of it connects to the gut microbiome and how it can be negatively impacted over long periods. Now again, I don't tell this to be, to be like scary. The intention isn't that antibiotics are, are a bad option. Again, I want to really emphasize here that antibiotics can be life saving. You can, in many cases antibiotics are necessary and if prescribed appropriately, they're something that individuals should take to help recover from an infection. However, I think the side effect that we're kind of really emphasizing here is that it can have negative impacts on the gut microbiome and that these shouldn't be ignored and should be really focused on as well to kind of really think about that path to recovery after antibiotics. So let's talk about what has the gut heal and what does it need? Well, first off, recovery can take time. Often this rebuilding of an ecosystem doesn't happen overnight. It can potentially take up to months, depending on what type of antibiotic. So here's a over time look at the difference in the gut microbiome and you can see now this is a particularly slow case, so particularly harsh antibiotic. But you can notice the dive down and then the slow increase back to normal, where even after three months they aren't necessarily back to baseline. It's closer to four or five months that we see that full kind of recovery from antibiotics. But there are things you can do to support this increase and really focusing on diet and environment can have a big impact as well as, as well as supplemental support as well. And really here the focus isn't necessarily on adding in particular taxa, but really rebuilding diversity and getting that ecological balance. Again, it's possible that you might not get the exact same gut microbiome composition that you had before antibiotics, but we're hoping to hit is a healthy, balanced ecosystem. Again, and I really want to emphasize this, that as everyone's gut microbiome is unique and different before they took antibiotics, often everyone's response and recovery is unique as well. So some people will recover very quickly. And while this is a common response, that's something we love to see and is really something we want to help support. Some individuals take longer even with additional microbiome support.

We have an interesting question here in regards to most of the bacteria we're talking about are in the Colon. Right. That's where the majority of these that we're discussing today and where we might be seeing these changes. There was a question about whether or not there's concerns about the small intestinal microbiome. Even that's significantly less population than the colon. And you know what effect antibiotics might have there and you know how to support that. Would there be anything special that you would do with that?

For sure. That's, that's definitely a really interesting question and I feel like something that's especially science needs to dive into more. So the majority of the population of your gut microbiome is in the large intestine. It's where, it's where you see them vastly populated. The small intestine often has similar individuals but in much lower densities and quantities. So how they are hit by antibiotics, I, it's, they definitely can be impacted, but the biggest impact often happens in the large intestine. So great question. I don't have a necessarily great answer about methodology that's different from the large intestine for the small intestine. I know communities can overlap there. So often things that you do to help support the large intestine can help the small intestine. But in a lot of the actions we recommend are things that are overall impactful across your, across your microbial community in general. So let's, let's dive into that though. Let's talk about what those actions are and what you can do and how this, how this has an impact. The first thing I always want to highlight is feeding the microbes you want to keep. So this is like again thinking of a forest fire that's wiped out the gut microbiome. What we want to do is really support and encourage those good bacteria to come back. We want to get those commensals back. And how do we encourage that? Well, for the, the, the gut microbiome, we need to give them the foods that they like to eat, which is prebiotic fibers. And prebiotics fibers are very common across your diet. If you're eating things like polyphenol rich foods, if you're eating a lot of greens, if you're eating the rainbow, these are all things that we want to really do just to support, to fuel those beneficial bacteria and their recovery. So I think we have a handout that's going to come out after this as well that'll go into guides for specific ones and specific recommendations. Your tiny health report also is really good at walking you through what particular prebiotic fibers would be useful. Really thinking about how to eat the rainbow. What particular aspects are really good, but you really want to give the food to the bacteria that you want to encourage. If we're not feeding those bacteria, it's really hard to get them to come back in good numbers. Another thing that we really highly recommend, and I think we have a poll here as well, is fermented foods. Fermented foods are really, really rich in all sorts of good bacteria. And especially when you've had kind of a depletion of bacteria, it really helps. I'm going to take. It really helps support reintroducing those beneficial bacteria and helping feed them as well. A lot of fermented foods also have postbiotics as well. So the bacteria that are helping ferment them are also producing really nice compounds that you're also feeding the gut with and helping prime it to get it back into state.

We love postbiotics.

Postbiotics are wonderful. I think this is something. Fermented foods are one of those that studies have shown can have an even bigger impact on your gut microbiome than prebiotic fibers. So often we stress both of them. Both of them are great. But often people are sleeping on the fermented foods and how impactful they can be. And I think there's a wide variety you could look for when you're looking for fermented foods. Remember, specifically, you're looking for things that have live cultures of bacteria. Again, postbiotics are very beneficial, but especially when we're thinking of receiving the guts. If you're looking at your yogurts in your yogurt aisle, you take a look for things that have live bacteria in them and are not and are not pasteurized. Also look for things that especially depending on which ones they are, like yogurts are also often guilty of having a lot of sugar in them as well.

Yeah, Best to get the plain version. And pickled foods do not always equal fermented foods. So not always the same thing. Make sure you're looking at the label. I even found some fermented salad dressing the other day, which was exciting.

Oh, that's awesome. I think it's getting more and more popular. Also. You'll. You'll see things that like. Like sourdough is a fermented product, right? There's. There's live, live yeast bacteria in there, but when you bake it, you kill it all off. So some of these will have. Have had live bacteria, live, live microbes in the process. But also think of what you're doing with them. This might also Be your. If you are taking any of these ingredients and tossing them into something that will kill all the bacteria, then you're likely not getting that. That live bacteria impact from what you're having.

Yeah, like kimchi fried rice.

Delicious. But potentially again, just an extra duration.

On top at the end. I think this answers one of our questions. Can we head, what holistic alternatives can we consider for adults or kids who take antibiotics that affect their gut? And I think this is, this is the list essentially of what to consider.

Yep, yep. And these are all good for like. Yeah, I think they, they're, they're good things in, in a lot of different states we often recommend. If you know that you're going to have to take antibiotics, you can start this even beforehand. Sometimes it's hard to take these individual foods while you're taking antibiotics. Again, we've looked through the different digestive upsets that happen in those cases. It's often good to kind of take a pause on things that are causing and related to that issue. But then these will help support them coming back as well. And studies have shown that higher rich food, plant rich food diets often correlate with faster recovery. So when you're thinking about that line is going to take months or weeks for me to recover. These are the things that really can help support that. And now what about, what about the other side of things? Other recommendations is really kind of more targeted towards that limiting the unfriendly growth. If we have those unfriendly bacteria popping up, what can we do to keep these in check? Often our recommendations, when we see high amounts of unfriendly bacteria popping up, are considering spices with antimicrobial properties. Again, these are things that you can add into your diet and add a diversity of them into your diet to really help support gut health and kind of limit the different unfriendlies from coming in also during this period, often suggests really limiting things that those unfriendly bacteria tend to feed off of. So we find often a high correlation between these bacteria and ultra processed foods. So being able to shift these out of that diet, particularly during a period where we know that they are more prominent in the gut, can be impactful. Artificial sweeteners and additives are also usually guilty aspects for things that feed those opportunistic pathogens and those unfriendly bacteria. And excess saturated fats is also a case too. Again, I'm not one to victimize entirely saturated fats, there's definitely a place in the diet for them, but especially when we have this after antibiotic recovery. It's possible that these could help feed the bacteria that we don't want to see overgrowth of in your gut microbiome. Really big impact too. I think people often underestimate that impact that stress and lack of sleep can have on gut issues. These are also things that are often cyclic. So having stress and lack of sleep can have gut issues. Gut issues will have, have perpetuates issues with stress and lack of sleep. So during your recovery period, as you're trying to really focus on getting that healthy community back, this could be a quick and easy way. Quick and easy, depending on who you are, to really kind of start that rest and recharge phase as well. Now let's talk a little bit about probiotics. So probiotics are really interesting with, with when we talk about antibiotics, we often encourage using probiotics even during antibiotic usage. Certain strains have been found to help prevent antibiotic side effects like diarrhea. So things like L. Rhamnosis, Lactobacillus, Rhamnosis, GG and Bifidobacterium longum are both strains that have found to be impactful to help prevent these antibiotic side effects. So taking them during and then after antibiotics can help reduce the odds of these types of symptoms. And often when we think about taking probiotics and antibiotics, we recommend you take them hours apart, ideally be able to take one in the morning, one at night. So we're not actively killing off the bacteria that you're taking at the same time, but a little bit of spacing works as well.

Yep, we did have a question here about that, about when to use antibiotics, when to use probiotics with antibiotics. So thanks for clarifying that, Kim.

I really want to. I think an interesting thing with probiotics too. Probiotics alone are often not enough. I think people think of what's wiped out. Often probiotics like Lactobacillus, we don't expect to colonize the gut. Bifidobacterium doesn't colonize in high numbers. So if you had a big wipeout and are using these strictly to try and get those good bacteria in your gut, they won't bring back a lot of the good commensals that you could potentially have. And actually some studies have shown that it actually slows down the amount of diversity that's coming into your gut. So I think it's one of those that you really want to use them really strategically and alongside a fiber rich diet, fermented foods or other Supports to really kind of get the rest of your commensals back into play. Yeah.

And appropriate dosages as well, right?

Yep, exactly. And I would say too, probiotic usage is likely much more impactful in infant ages as well. Again, we gave that example of the baby who had the Bifidobacterium wiped out. We recommend those Bifidobacterium probiotics to help supplement that again and improve the amount of bifidobacterium in the gut. There we expect actual colonization versus adults, where sometimes we see that colonization, but really we're expecting things like the color bacterium, the rest of those anaerobes to come in as well. These microbial ecosystems rebuild slowly and dynamically over time. That support for them isn't often a quick fix. It's great if your ecosystem can kind of bounce back naturally, but often you have to give it a little bit extra support to get to that baseline and have that recovery happen quicker. And that repeated antibiotic use actually often resets this clock. So if you were knocked down, then take antibiotics again, you, you can imagine more diversity and longer time to get back up to your standard community. So after each, I basically recommend after each antibiotic course or during it, take supportive action, then to try and recover as quickly as you can and make sure that you get those commensals back into the gut.

Yeah, we did have a question here about when kids take antibiotics, specifically babies, do their microbiomes really truly recover? Diversity?

Yeah. And I think that we. One, we have seen plenty of infant microbiomes that do. So I think it is definitely possible and it's not necessarily lifelong scarring because they take antibiotics. Even though often babies are given frequent doses of antibiotics, often for ear infections or other concerns. And each of these can have long term impacts. I think the biggest risk here is to not check in and not help support that recovery. So, so taking action quickly, making sure they're getting a Bifidobacterium probiotic, doing something to support that Bifidobacterium gets them back on track after they've been kind of shifted off that course. Yeah.

The appropriate fiber and the colorful diet is also going to have a big impact in that population.

Also if, if breastfeeding can have a big impact as well. So if you're giving. So bifidobacterium feeds off of human milk oligosaccharides, which are in breast milk. So if you continue to breastfeed while giving antibiotics and after that can also really help support, give that prebiotic fiber to keep community Thriving. I think the one thing I recommend is often like don't stop breastfeeding even if given antibiotics. I think it's also an interesting case if mom is given antibiotics as well. What to do in those cases? Some antibiotics can be transmitted through breast milk to baby, but it kind of depends on what particular antibiotic and whether or not mom can continue to keep breastfeeding during that period.

Yeah, there was a question actually about antibiotics during pregnancy, Kim, in regards to whether or not that impacts the infant or the fetus. I guess at that age.

Yeah. And actually I do have, I have a case study specifically goes into one of these. This was during gbs. So right during delivery and labor, short term, it definitely can. And we often think of supporting both mom to get her gut microbiome back into estates that will, that will support baby during delivery as well as baby too, in case they have longer term impacts. Well, with baby, their first community is what mom's community is. So she's had a lot of antibiotics and she's wiped down kind of the things we want to colonize baby, then it might be harder to see those coming in really early on during those first months to help support baby's gut. And then the last thing I really want to say here for recovery and diversity is it's really important to monitor and adapt over time. Often you'll try a particular probiotic, a particular strategy, and you might end up in this kind of different states. What happens if you, if you end up in a less resilient state? It's often a longer journey and something that really takes time to recover and end up better after antibiotics. Antibiotics is just one of those things that can knock you off track. It's often pretty dramatic, but life will always have little, little impacts, little disruptions that happen to your gut microbiome. And it's really important to support gut resilience. This is one of our new metrics that we released this year that really focuses not just on whether your gut microbiome has the healthy commensals in it, but how susceptible will it be to disruptions, things like antibiotics. A healthy high gut resilience score means it is more likely that after a disruption you go back to your healthy states. While a low score, it makes it more likely that you're going to see a lot of change in your gut microbiome, often not for the better. So what you want to build up, even between antibiotics, even if you don't have antibiotics in the near future, you never really know when these might be needed. So building up really strong gut resilience that can support and like handle the hits of antibiotics can be really impactful towards your gut health in general. And this is at all ages. I would recommend this for, for children just as much as adults, case studies. And I know we've got some Q and A time too, so I'm going to go through these a little bit quickly, but I'm happy to answer more questions or dive into them a little bit more as well. And the first one we have is a pregnancy case study. This is a healthy individual who took antibiotics because they were group B strep positive. Now for those who don't know, group B strep is one of the bacteria that's tested for really early in pregnancy. If you test positive for it, the doctors in the US typically prescribe antibiotics before delivery. Group B strep can potentially cause at very low rates, but potentially can cause infection in babies, leading even to death. So this is why in general the US has this practice of giving antibiotics. In this case they were given penicillin G, which is a narrow spectrum antibiotic effective specifically against those gram positive bacteria and it was given via iv. So this is again supposed to be a very targeted approach to really focus on that group B strep and not necessarily take out everything. What we see though is after those antibiotics we see that drop in those beneficial bacteria. So while this focuses on gram positive bacteria, a lot of our commensals are also gram positive. So even targeted antibiotics can have longer impacts. We see a drop in Bifidobacterium, Vaecalobacterium and Akkermansia. Akkermansia I believe, going to zero. So that that was the one that was wiped out afterwards. And we see this rise of disruptive microbes after this. So an increase in Pseudomonas and Enterococcus and Campylobacter that had previously not been present in the gut microbiome. So these things acting as, as opportunistics in this community that's been wiped down after, after the antibiotics. We also see this drop in short chain fatty acid production, specifically in propionate and acetate that goes alongside this drop in diversity. Then if we look at baby after baby was born, we see a sample there as well. Here mom dropped down in Bifidobacterium. Bifidobacterium is one of those that we really want transmitted to baby during delivery or afterwards. This helps seed baby's gut. You can see mom didn't have any Bifidobacterium in This case as well, we see 0% Bifidobacterium in Babylon. This 33% enter Bacteracea. So again, there's a lot of potential things that could have been resulting in why we see this increase in Enter bacteracea and low BIFs in baby. But in this case as well, we think of those antibiotics potentially as well causing more long term impacts. In this case, actions are pretty straightforward. Supporting baby is as straightforward often as a Bifidobacterium probiotic. That can really help increase those amounts and help support dropping the Enterobacteraceae. Then there's a wide variety of those dietary and supplemental actions that mom can take as well to support her gut and get those beneficials back in. Then for here is an example of a healthy adult who took antibiotics after a sinus infection. This time Amoxicillin. So a broad spectrum antibiotic taken orally for recovery, they increase fermented foods and Akkermansia probiotic with HMO support. Here we see the antibiotics are taken between these two samples. You see the massive drop in Akkermansia, the increase in Enterobacteraceae very characteristic of antibiotic usages. We also see relatively quick recovery in this case. So here Akkermansia shoots back up, which is great to see, and Enter Bacteracea comes back down. So it looks like mostly a blip of a sample over the course of a year. That's great. However, some metrics did not recover. We're still seeing antibiotic richness after that period leading up, even six months after antibiotics are taken, as well as antibiotic abundance. So recovery in some ways, but not others. So something's still disrupted. And in this case, I think what's really cool here is we see that Akermansia increase with the Akkermansia probiotic and the additional support there. But there's probably also additional actions that could be done to really support bringing down richness for long term gut health as well. And then finally, this is a child that took multiple courses of antibiotics for ear infections. So four to six courses before one year for recovery, they had increased fermented foods, a Bipobacterium probiotic and HMO support. And here we can see more of the long term impacts. It was more of a journey. Here we see the antibiotics, we see a slow recovery of Bifidobacterium, but it does increase quite a bit to healthy levels. And it takes time too to see that antibiotic richness drop. But over prolonged support we see that go down as well. This is A case too where there's a lot of things to support as they get older. With the Rainbow Food Tracker and checking digestive capacity, even long term support here we see digestive capacity is looking good. While we saw that antibiotic blip really early in life, we're seeing healthy amounts of digestive ability here. Fiber, digestion, complex sugar, and overall healthy guts, even with multiple courses of antibiotics. So yes, in general we do see recovery, and it's not something that necessarily has long term scarring if supported. So just to reiterate, healing after antibiotics, antibiotics can save lives, but they can also leave an impact on the gut microbiome. Some symptoms are immediate, but some have long term consequences. And really helping with fiber and fermented foods, taking actions can really help recovery in the long term. And with that, I think we can jump into any additional questions that we have.

Awesome. Thank you. Kim was really helpful, informative, and I just really love that wildfire analogy. It just makes so much sense. So thank you so much for that information. We have a lot of questions and we went through a few of them during the presentation, but let's get into some of them. One of our participants asked, does baby inherit mainly their microbiome from mom or dad too?

Yeah, no. This is a really cool question. And the answer is both. You get it from both mom and dad. Mom is often the first source, right? Even during delivery. If baby is going through vaginal delivery, she's coming, the baby's coming in contact with vaginal microbes and stool microbes, and all of those are what should be seeding baby's gut. So that's the first instance. As well as breastfeeding, mom is also passing and feeding bacteria through breastfeeding. However, dad and family and everyone else plays a role too. And these are also kind of donating to bacteria and we can donate bacteria to baby. And we can see influences of every family member in baby's gut microbiome. So all of those interactions are important and impactful. We think of gut health. It's a family experience we share. Gut microbes having strong gut health in each of those family members can really help support baby.

Even pets can influence the microbiome for us and babies. So it's really exciting. We had a couple of questions about kind of steroid use, tropical creams, corticosteroids, and the questions were generally around, do those products potentially have a effect on baby's microbiome and specifically maybe Akkermansia. What has your experience been with that?

Oh, that's a really good Question. And I think it's something that's, that's really hard to unentangle, I guess because there's a lot of impacts that it could be having a gut microbiome and particularly Akkermansia. Akkermansia is one of those especially in very early ages. So we don't, we don't see it come in until a little bit later as baby becomes more, as baby and child becomes more established on solids and often even in adults, we need to see like specific dietary support to really make sure it flourishes. So we think Akkermansia is very important. But what exactly caused it to be absent in young children I think is still, still kind of a question. And what we can do to better support that age, making sure it comes in, I think is also a really, really active question. So high level. No, I don't know. I think that is something I would, I would love to try more into.

Yeah, we, we did collect that information in the tiny health questionnaire and so I'm sure we'll be able to extrapolate more about that in the future.

And I highly encourage, since I have an active audience here, like to check out our research editions because we are actively asking a lot of questions around very specific topics like the oral gut microbiome and the gut, the oral and gut microbiome axis as well as the aging microbiome. So if you're interested in research and helping support these, these endeavors really encourage you Checking out that page as well.

We had a question about antibiotic course length. Kim, you mentioned if you don't finish the antibiotic course, it can contribute to antibiotic resistance with doctor use. Doctors using cookie cutter approaches or you know, standard recommendations, it seems they always prescribe longer versus shorter. Would taking too long of a course also contribute to.

It got cut off. So I don't know. Yeah, yeah. No, I think this is definitely, this is a question that I think about a lot and actually comes up relatively frequently because we do see that evidence that often, often doctors are leaning towards longer, longer courses of it. And the concern here is with antibiotic resistance that you should take all of it. Right. So if you, if you allow some small community to stay of that pathogenic bacteria, then it is more inclined to repopulate and have a resistant population. And then you'll need another round and another round. Which is why the huge emphasis on finishing the courses you're given, however, and this is often in the person who is prescribing its hand is really important to make sure that they get the appropriate prescription because then if they are taking a longer one than necessary, we're adding more antibiotics than needed.

Their next question was about any, from your experience as our head of science, any research showing antibiotic use and autoimmune disease connection.

So this is actually one of our big topics that we're diving into in the next year as well. Autoimmune diseases are something that is, is really kind of tied to a lot of different factors and it's something that like the gut and the gut microbiome is potentially playing a large role in, as one of those factors. And I believe hitting it especially with antibiotics relatively early can have long term impacts. And we see this really dramatically in certain anti, in certain autoimmune diseases and in some autoimmune diseases less clear. So I think it really probably depends on the timing of it and the timing of those antibiotics. I think one of the biggest kind of mysteries that we're still hoping to solve here around antibiotics is their long term impacts are not necessarily well characterized. So to some degree we're seeing these conditions develop and they have a healthy gut microbiome now. Right. So you've done everything for your gut microbiome now, but that doesn't necessarily say what happened to your childhood. And sometimes long term antibiotic usage early on in child could have impacts in the training of the immune system and how the immune system reacts to different components that are lifelong even after your gut is fixed. So I think there are definitely really impactful windows here where we're going to see influence more chronic conditions than others.

Which beneficial bacteria are best at avoiding the forest fire of antibiotics? How does the bacteria protect itself and how can we support that?

Yeah, no, that is a great question and something that I think like I would love to have better ways to support it so they could hide. Right. Like usually the, the things the commensal bacteria don't have necessarily as much defenses against this. Usually it's those pathogens that are holding and like are holding different reserves of antibiotics. So it's really unfortunate that E. Coli, which causes infections, also has the most antibiotic resistance and defense against antibiotics. Maybe that's not so surprising given the evolutionary pressures here. So some of the things that, that can be done here a lot is like the, the mucus, the, the mucus lining. Often things that are really embedded there might be getting a lower dosage than the things that are kind of a little bit more out towards the center. If you're thinking about these antibiotics coming through your gut, they're having a biggest impact on things they can directly interact with versus things that are kind of hidden away in the mucous lining are going to be harder for them to interact with. So sometimes after antibiotics we actually see a spike in Akkermansia, which is really interesting. And that's not necessarily because Akkermansia is a opportunistic pathogen taking, taking advantage of the forest fire. It's just the thing that's really good at maybe hiding under the dirt a little bit as the forest fire comes through and then it pops up again in higher levels as everything else is knocked down. And in general with, with such a great diversity of commensals, it's hard to protect everything. I think often we think about antibiotics again necessary life saving. But what can we do to really build back that community then in quick force after the use of them?

There was a question here from Lauren. She said we had the absolute best experience after our tiny health protocol with my almost 2 year old. We completed our protocol in July and he has yet to miss a single day of school this year due to sickness. Awesome. With that said, I want to understand the best way to support his gut if antibiotics are needed in the future. What are three to five action steps I can take for my kids or myself if they actually need antibiotics in the future?

So I think this is one awesome to hear that everything is going well and I think it really kind of stands that testament of this connection between your gut microbiome, especially at early ages, and your immune system. So often when we think of supporting your immune system, a healthy resilient gut will help support that and will help support the need for antibiotics in the future because hopefully you're not getting infections right if you have a healthy system that can help prevent these infections to begin with or a viral comes through and it manages to not become a bacterial infection. These are all great things that are preventative even before antibiotics are needed. Now if antibiotics are needed and of course this has happened in my family as well, healthy and everything going well and you never really know when that antibiotic is going to come out to you kind of unexpectedly. I usually recommend like getting, getting ready to support. So I immediately think of probiotics I can give during. So things like those, those L Rhamnosis, gg, the bifidobacterium ones depending on the age. I've got a little kiddo and I want to make sure biff stays prominent in their gut. So I often focus specifically on the bifidobacterium replenishing. I'M giving it at the same time as the antibiotics. And then after the antibiotics, I continue with that probiotic. And at the same time as this, I'm also really focusing on what fermented foods can be giving and giving certain, certain amounts of servings of fermented foods during this period just to really support those good bacteria and, and especially after the antibiotics are over, really thinking about replenishing that community. So I guess three to five steps, probiotics during and keep them after as well. Once the antibiotic course is done, really thinking about those, those foods, those fermented foods, those fibers to really help support that community. Come back. You can do it during as well. But I find especially afterwards, we want to make sure that that's like the, the worst damage has been done. Once they finish, let's make sure we're supporting community. Awesome.

Okay, amazing answer. Let's do three more questions. I think this first one's easy. How is the gut resilience score calculated?

Yeah, no, this is a. This is what I'm particularly proud of. I had a large hand in calculating this one. So we actually looked at a number of resample, a number of individuals who had, who had taken multiple samples and looked at how different their samples were. And we found distinct patterns. So some individuals would have. Have the same basic composition after every single sample, regardless amount of time and regardless amount of what they did in between. Right. This includes like, you know, I went on a trip to Bali, I went on a adventure here, I changed my diet here and here. And yet every single time, very similar composition. And then we had other people that fall in that exact opposite category where regardless the amount of time here, almost like, you know, after controlling for the amount of time, we see large shifts in their gut microbiome and it was consistently changing in one direction or another. And this actually could be tied to patterns in their gut microbiome. The presence of certain bacteria and function predicted whether or not we would see high resilience or not. So you could actually cultivate a community of resilience versus have a community that was more likely to be disrupted even before that disruption happened. Here we're using a machine learning model to specifically do those predictive pattern characterizations and then build that into our algorithm. Even if you only sampled a single time, our algorithm will tell you, do you look more like those guts that are going to stay stable and healthy over long periods, or do you look more like those guts that are basically an ocean or a boat on the waves and it's just Going to be up and down, up and down with every single life change. This helped us define that there will always be kind of exceptions here where particularly long doses of antibiotics, even if you have the most resilient gut, is not going to be able to stand up to it. But at least this gives you a feel for how resilient your gut is to those typical day to day interactions.

I received loads of antibiotics as an infant kid and no breastfeeding, raised very low fiber and ultra processed foods. I messed up my GI badly. Is restoration possible after so many insults? Yeah, yeah.

I think this is something that a lot of us are in this boat especially just thinking of like the amount of decades of work that's come out and shows how big of an impact low fiber, ultra processed antibiotics and breast milk have on, on the gut microbiome. These early stages have, have a big, big impact on, on your gut composition as well as like your lifelong chronic condition stasis. So what about, what about the gi now what's nice about the gut microbiome is that it is influential and you can change it so you can support your gut microbiome and that can have a big impact on potential severity of symptoms depending on what conditions you have as well as like, you know, kind of protecting for the future. Like your gut microbiome often gets worse as you age now so often depending on where you are right now, now is not the time to stop thinking about your gut microbiome that it's already too far gone. It's the time to start preparing for as, as more insults will come, more disruptions. How do we get it in the healthiest state? It will be to help weather those storms as well. So I think what's nice always opportunities to improve and to get into a better state. Although yes, those lifelong impacts are kind of often hard to measure and some of them are not going to be necessarily reversible at this stage.

We had another similar, kind of similar question that was asking about like specific GI diseases and whether or not the tiny health tests can help with that. Do you want to speak a little bit Kim, on kind of the approach of being a wellness test and how that can support.

So the tiny health test is a wellness test. We do not, we do not diagnose, we do not offer medical advice at all. However, it can be very helpful with understanding what your gut composition is and things you can do to better support the gut composition of your microbiome. So you can think of things specifically as in like we, we know what a healthy Gut microbiome can do. We know it can produce short chain fatty acids, we know it's involved in inflammation, and we know it's involved in like a lot of different kind of digestive paths of it. So your report will kind of dive into each of these different metrics and give you, give you tips and recommendations to help improve and support these different aspects. And for a lot of these, like for different conditions, sometimes we have more information about the associations and metrics that are important in them. Sometimes general support can help these different conditions. So not every condition do we currently have associated associated markers for, but many we do and can can actively help you specifically focus in on areas of your gut that might need extra support.

Last two, because they got a lot of votes. Number one is how do you know that fibers and fermented foods will not feed bad bacteria as well as good bacteria? I assume it's what is on the inside that would determine.

Yeah, no, I think this is a, is a great question. And they're like, what's nice about fiber and fermented foods is that they could potentially like you're, you're giving food in general to the bacteria. We do know that often these fibers and fermented foods are more associated with commensal bacteria than the opportunistic ones. But really we're talking about a bit of a numbers game again, right? What we want is an ecosystem. So if you are, if you are giving fertilizer and really kind of encouraging all sorts of good bacteria, even if the bad can eat it, those good are going to help protect your community and end up with a balanced community. If you're not supporting those good, then the bad will just win. Right? The bad are good whether or not you give fiber. Even if you're eating those ultra processed foods and the, the kind of, the high saturated fats, all that stuff, the opportunistic pathogens are still going to be a. Okay and thriving. So what you need then is to support those other ones that don't come in unless they, they get the food that they need. Awesome.

Thank you. All right, last one. My tiny health report suggested I take a natural antimicrobial, oregano oil to fight off my overgrowth. Do natural antimicrobials fight cause the same response in the gut as antibiotics prescribed by doctors?

Yeah, no, I think this is a, is a great question and I think there's a lot of different potential antimicrobials you can talk about and often they are often not discriminant either. So I think it's something to think about that, especially if you're given alternatives. Antimicrobials that are not specific antibiotics but have the same properties will often not specifically target one versus the other. The difference here is often antibiotics have a much more massive. They've been specifically designed to have a really massive effect here. So with the mass wipeouts versus often low level antimicrobials are much more subtle impact. So things like, you know, adding garlic or ginger to your. To your food is going to have a much more moderate response than if you had like, you know, the antibiotic, which is going to be a very concentrated bacteria wipeout kind of response.

Yeah, it's like a river versus a flood. Right. So there's a good, a good way to kind of understand the difference there. All right.

Oregano, oil. Often you like, especially if you're working with a practitioner, there are certain, there are certain antimicrobials that you don't want to take long term because they can have negative impact towards the community as well. So often some of the harsher antimicrobials should be taken with practitioner advice and even then really targeted towards what your results are looking at. So you're not just wiping out that beneficial community, too. Yeah.

And that's why retesting is so important, because you really need to be implementing some sort of plan for how you want to improve your gut and then be retesting afterwards to see if did that plan actually work? Did you do it long enough or too long? Or do we need to, you know, customize it a little bit more and make some other changes? So, yeah, that's why I think the retesting of your gut is just so powerful, because then you can actually see, hey, did this work? And if so, how well do we need to keep doing it? Do we do something different? All right, well, thank you, Kim, and thank you everybody so much for all your fantastic questions. Have a great day, everyone. Take care.