Andrew: Really good. All the more better after not stumbling over your introduction. But welcome. I think we really have to start with… I’ve been introduced to New Zealand gold kiwi fruit powder previously, but can you explain for our listeners and our viewers exactly what it is, and where is it positioned?

Ping: Sure. So I think before I introduce Livaux, it will be good to talk about the company that produces Livaux. So we’re from Anagenix. So for those of you who don’t know, Anagenix is a New Zealand ingredient manufacturer who specializes in producing whole clean, whole-fruit ingredients for nutraceuticals. So we only use locally grown fruits and that gives us full control over the whole supply chain. So Livaux is one of our many flagship products. So it is, like you said, it’s made from gold kiwi fruit. It’s a free-strike powder, and it’s positioned as a precision prebiotic that’s meant to target keystone bacteria that leads to other benefits down the line.

Andrew: Yeah, sure. So talking about keystone bacteria, you know, in the past, we used to think it was all lactobacilli, and then we realized, actually, lactobacilli aren’t one of the major dominant species in the gut. Can you take us through these keystone bacteria? There may be indeed other microbes, but let’s stick to bacteria, keystone bacteria, and what makes Livaux so integral in helping them to thrive?

Ping: Okay. So I think before we get into that, it’ll be good to talk about what keystone bacteria actually is or are. So keystone bacteria are critical players that help to keep the gut healthy and balanced. So they may play important metabolic functions like breaking down starch or polysaccharides. They may also be involved in producing short-chain fatty acids, so these are important compounds to keep the gut healthy.

So in the case of Faecalibacterium prausnitzii, what we call F. prau for short, it is one of the most abundant bacteria in a healthy gut. And we know from many research that lower levels of F. prau is consistently associated with different conditions like IBS, IBD, and increasingly, a number of metabolic and neurological conditions. So the key role of F. prau or the key function of F. prau lies in the metabolites that it produces. So it is one of the major butyrate producer in the gut. But besides butyrate, it also produces other metabolites that help to regulate inflammation.

So what they target, or what they inhibit is what we call nuclear factor kappa B, which acts like a master switch of inflammation in the body. So besides that, F. prau also interacts with cells in the immune system. So these are your dendritic cells, your regulatory T cells. And this interaction just helps to keep the immune response under control.

But I think the most important thing that we have to remember is that F. prau, the benefits really come from the butyrate it produces. So butyrate does not just reduce inflammation, it also plays so many different roles in the body. It feeds your gut cells, it keeps your tight junction cells between cells functioning properly, and it also just helps keep everything moving along properly.

Andrew: Ping, thank you so much for shortening Faecalibacterium prausnitzii to F. prau because I’ve stumbled over that bacterial genus and species so often. So we’ll call it F. prau from now on. Can I ask, why is it so meaningful that we’re engaging F. prau with this fiber, with Livaux?

Ping: So what makes… Well, we’ve talked about why F. prau is so important, because it’s a key butyrate producer, it helps with managing inflammation and immune regulation in the body. But a key thing about F. prau is that it’s extremely oxygen-sensitive. So that means historically we’ve really struggled to deliver it or produce it in a stable probiotic format.

Yeah. So we are seeing advances in encapsulation technology, and I believe Designs for Health is leading the charge in that. But before that, Livaux was the first and only probiotic that has been shown to increase F. prau and increase it by twofold in certain cases. And this is such a big deal because you have this bacteria that everyone knows is critical for gut health, but no one seems to be able to target it in a replicable way. So that’s why.

Andrew: And you spoke about butyrate previously being one of the most important metabolites of F. prau. So how do you translate increases in butyrate into clinical outcomes? I always default to short-chain fatty acid production in like vaginal microbiota and vaginal conditions. But where else?

Ping: Well, butyrate and the other short chain fatty acids, but butyrate, especially, is arguably one of the most important postbiotics or gut fermentation products that comes out from gut fermentation, and the research on it is very well established. So it plays a couple of key roles in the gut.

So, number one, it feeds the cells in your colon. So we call this the colonocytes, and that helps to keep the gut barrier functioning healthy. So it keeps the bad bacteria or the bad microbes, or whatever you want to keep out of your circulation out while still allowing nutrients to pass through. So that’s the first bit. It’s the primary energy source for colonocytes.

The second thing is that butyrate stimulates mucus production. So this forms a thick layer in your gut that becomes the first line of physical defense. The third thing is that it also helps to upregulate tight junction proteins. So think of the glue between the cells in your gut that helps to regulate what comes in and what stays out. And beyond that, butyrate also interacts or inhibits certain protein complexes, so things like nuclear factor kappa b, or histone deacetylase that act like master switches for inflammation in the body. But these are the effects that we normally see in the gut. But beyond the gut, butyrate also has effects.

So, first thing. When your gut barrier is functioning properly, we prevent or we reduce the translocation of toxins and bacterial fragments into the circulation because we believe that this leads to low-grade inflammation. But butyrate can also act like signaling molecules that take part in multiple gut-body axes. So things like your gut brain axis, your gut immune axis, your gut metabolic axis. So butyrate is… And Livaux is not just a gut story. It has whole-body implications.

Andrew: Yeah. And how important is this combination of, you know, when you’re talking about producing short chain fatty acids like butyrate and then also looking at the assessment of the change in the microbiota, particularly F. praul, when you’re assessing true clinical efficacy in conditions?

Ping: I would say microbiome change, being able to see microbiome change gives us a window into what might be happening when someone takes a supplement. So this helps us move beyond issues that are typically associated with just symptoms reporting, so things like placebo effect or other non-specific factors.

So when you have both symptom improvement and some indications of microbiome change, this gives us indication that there might be an underlying biological mechanism at play here. Yeah. So, for example, in the case of Livaux, we know from clinical studies that it increases F. praul. But this is also seen alongside improvements in bowel function and GI comfort.

So we’ve talked about… Okay. F. prau, it’s a major butyrate producer, and butyrate is really important for keeping your gut cells healthy. But beyond that, it also helps with gut motility, nerve signaling, gut hormones, and basically just helping to keep everything moving along. So that sort of tells us the whole story.

Andrew: Yeah. You know, this is so much more than my original introduction to New Zealand Gold Kiwi Fruit because all… Like, my original thing was just used in IBS constipation to help people move more regularly, but now, this is expanding so far beyond that. So tell us about, like, do you think that we’re entering a phase where we might be using targeted fibers rather than just bulk fiber for this, let’s call it a targeted microbial modulation, if you like?

Ping: I think so. Because if you look at traditional fibers like your psyllium or your traditional prebiotics like your inulin, or FOS, or gauze. So if we talk about fibers like psyllium, they do have benefits in improving gut transit, softening stool, but their effects are largely physical, and not all of them are fermentable. Whereas prebiotics, traditional prebiotics like inulin, FOS, and GOS, they are readily fermented, but their effects tend to be broader, less selective across the microbiome.

But with Livaux, that’s… And one other thing. So these traditional fibers of prebiotics, they are often taken at much higher doses. So a couple of grams normally, but it can go up to 20 grams, for example. And what makes Livaux different is that it appears to work at a much lower dose of 600 milligrams and while conferring selective health benefits. And we’ve seen this in our clinicals.

So we’ve had two clinicals in people with functional constipation, as well as healthy individuals with occasional constipation. And Livaux has actually been shown to increase F prau by over 100% in some of these individuals. Yeah. And that’s why we are so excited about this.

Andrew: Yeah, absolutely. And one of the other things, I guess, because you’ve got total control over the product from, you know, seed to shelf, if you like, you can control things like contaminants, things like testing for pesticide residues, and all of those sort of things, whereas, normally when we rely on even great foods, I think you get some great foods like a punnet of raspberries, great dose of fiber, versus things like psyllium.

Fantastic dose of fiber, but have you ever looked into the chemicals that they spray on raspberries? It’s huge. So this is something that’s actually quite exciting to me with regards to a targeted supplement like this, in that, you grow it. You control everything in the line.

Ping: So in the case of Livaux, we source our kiwi fruit from Zespri-approved orchards. So we know that we are getting the best quality food to make our products.

Andrew: Gotcha. And I would imagine, though, that the obvious test for pesticide residues and things that would have to be done.

Ping: Of course. Yes. And we would have all the certifications and everything to back that up.

Andrew: Yeah. You might get that from food. No way. Ping, can you tell us a little bit about how Livaux differs in terms of fermentation profile, the tolerance that you might particularly expect, particularly in sensitive patients like our IBS?

Ping: Sure. Okay. So if we look at traditional prebiotics like inulin, FOS, and GOS, these are quite simple chains of simple sugars. So they feed a broad range of bacteria in your gut. And because of their simple structures, they are broken down quite quickly as soon as they reach the gut.

So this is what we call the proximal colon. And this rapid fermentation by bacteria is what drives that burst in fermentation that produces gas. So things like hydrogen or carbon dioxide. And that causes things like bloating and gas that a lot of individuals, especially those with IBS, my experience taking this kind of prebiotics.

Where Livaux is different, it’s from the complex kiwifruit pectin that it contains. So kiwifruit pectin contains…it consists of a core of galacturonic, acid and it’s decorated with many branches of sugars, or methyl-acetyl branches, that must first be stripped away by bacteria before other bacteria can access the core.

So what happens is that this significantly slows down fermentation process because you need a whole consortium, what we call, of bacteria to break this fiber complex fiber down, and this slows the fermentation along the whole colon. And as a result, you get less gas production and also less symptoms. So one thing to note is that unlike inulin, FOS, or GOS, kiwifruit pectin found in Livaux, it’s low format. So that means IBS-sensitive patients are good to take them, and it’s suitable for all populations.

Andrew: Gotcha. And what about using Livaux alongside probiotics to enhance colonization and the effectiveness of these other probiotics?

Ping: So you can think of Livaux as essentially doing two things. Number one, it helps to prepare the gut environment so that incoming good bacteria, your incoming probiotic strains, have a better chance of surviving and functioning effectively. And this is, again, down to the kiwifruit pectin, because it’s slowly and progressively fermented, it spreads the production of short-chain fatty acids all along the colon. And this may help to lower the pH in the gut environment, and these are all conditions that are more conducive to the growth of good bacteria. So that’s the first thing.

The second thing is, again, comes back to pectin being a sustained food source, not just for F. prau, but for a whole consortium of bacteria in the gut. And after they have broken down this complex kiwifruit pectin, they produce metabolites that further support the wider microbial network. And, you know, microbes in the gut, they don’t exist or operate in isolation. They feed off each other. They work together to break things down.

So Livaux essentially prepares the gut environment, and it also provides food for the good bacteria. So, in fact, we’ve seen this in in vitro studies. So, for example, in a study using the SHIME model, which is an in vitro gut simulator, we’ve seen that combining Livaux with probiotics actually significantly increases butyrate production by up to 261%, as well as increase F. prau levels in the distal colon. So that’s the furthest part of the colon from our small intestine.

And this is compared to just taking or having the probiotics alone. So that’s how well it works. And we also know from other in vitro studies that we’ve done that doses as low as 25 milligrams of Livaux has been shown to enhance the growth of beneficial probiotic strains by up to 200%. Yeah. That’s why we’re…

Andrew: Wow. That’s pretty impressive.

Ping: Yeah. We’re really excited.

Andrew: So I can see, obviously, that this would help patients with leaky gut, because you’re setting up the whole soothing of the whole terrain. But what about patients with, say, systemic inflammation or immune dysregulation?

Ping: Again, I think this comes down to supporting the gut barrier function, which is really one of the main interfaces between the outside environment and our immune system. So what people often call leaky gut is increased intestinal permeability. So things that shouldn’t go into your circulation start going into your circulation because this…tight junctions between the cells the glue that is holding the cells together become looser, less selective. And when all these different compounds get into the system, it can lead to low-grade inflammation.

So that is what can lead to systemic inflammation. It can lead to immune dysregulation. So that’s where Livaux, again, comes in because it increases F. prau, and F. prau is a major butyrate producer, so, then, it helps to support all these different functions like the gut barrier and even gut motility and the overall gut environment.

Andrew: So I can really see that Livaux can be useful in areas outside of gut like, you know, let’s say inflamed skin, atopic dermatitis, metabolic health. Can I ask, and I’m not asking if there’s any research on this. But have you ever heard of Livaux bringing back that immune regulation in such distal conditions as things like, I’m going to put it out there, Hashimoto’s thyroiditis. Have you ever seen that gut balancing being that powerful that it can bring back the balance with the thyroid function?

Ping: Not that condition in particular. And I think what we have to note is that the research in this is still quite early when it comes to other indications. But I would say it’s really promising just because of the Livaux F. prau butyrate link. And we know from increasing research that butyrate is involved, not just in the gut, keeping the gut regular or healthy, but it’s involved in all this different gut body accesses. So it can…definitely has the potential to affect skin health, hormonal regulation, metabolic health, immune regulation, all these sorts of different things. Yeah. But not, perhaps, right now, we need to watch this space to see what happens.

Andrew: Yeah. It’ll be very interesting, though, to indeed watch this space. You know, one of the things that really impresses me, though, is the low dose that’s required to affect a response. That’s really quite dramatic, particularly when you’re considering fibers and when you’re considering the dose that patients need to take of these fibers, then you’ve got to think about compliance, and it drops off dramatically. So something like this is so easy, it’s just amazing.

Ping: Yeah. Definitely. And I think. So, really, how you can think about this, is I always like to use the analogy of traditional prebiotics versus Livaux is kind of like comparing white bread, white rice versus brown rice and whole meal bread. So through our proprietary processing method, we are not, you know, instead of isolating a single compound, we are essentially just removing the water from good quality gold kiwifruit and we retain everything else that is naturally present in the fruit matrix.

So these are things like, of course, the fiber, the kiwifruit pectin I mentioned, but also the polyphenols, the vitamins, and the minerals, and all the other little compounds that you just don’t find in those stripped back, isolated ingredients. And we believe that is why we do see such an effect with Livaux, and that is also why we are a five-time NutraIngredients Award winner. It’s this complex matrix that contributes. Yeah.

Andrew: Okay. So the next question is do you think we’re moving away from a model where we prescribe nutrients based on microbiome targets. Sorry. Not away, towards a model where we’re looking at these keystone microbial species rather than just treating symptoms?

Ping: I think so. I think as sequencing technology becomes cheaper and more accessible, we are getting much better at understanding the gut microbiome and what species really matter and what functions, potential functions, they may be playing in the body, in the gut.

And so there was actually this paper that was recently published in “Nature” that looked at over 30,000 individuals across the U.S. and the UK, and they found that certain gut microbes were consistently linked to certain cardio metabolic health markers. And that’s really exciting because now that we know what microbes actually matter, and if we increasingly understand the roles that they play, then we know which microbes to target.

And once we know what to target, then we can start to think about, okay, how can nutrition make a meaningful change or shift in these microbial populations? So, for example, we know that F. prau, really important, and lower levels have been linked to conditions like IBS, IBD, and a whole host of other conditions. So how do you target it? So Livaux is one of the only prebiotics, the only prebiotic that we know of that consistently has been shown to increase F. prau and increase it by 100%.

Andrew: Significantly. Yeah. Absolutely significantly. Okay. So last question for you, Ping. And that is if a practitioner isn’t currently using Livaux, what would you say is one clinical condition where utilizing it could completely change their outcome? What would it be? What would be your callout?

Ping: From a research perspective, the clearest starting point would be someone who likely has lower levels of F. prau. That’s where the evidence for Livaux is strongest. So, in particular, people with constipation or, you know, functional constipation or occasional constipation because that’s what we’ve seen through our clinical studies. But beyond constipation, you can also think about there are other signals.

So lower F. prau may be associated with things like lower fiber intake, people under stress, or inflammatory states, or people who are taking antibiotics. So I wouldn’t say it’s a particular condition, but really indications where you think that the gut environment is compromised and you want to support that. Yeah. So Livaux would be a really, really good solution.

Andrew: And certainly, if patients are…or practitioners, forgive me, are undertaking… Let me use my English there. And certainly, where practitioners are utilizing microbial testing and they’re seeing low levels of F. prau, then that would be the signal, really, to use Livaux. That would be the thing.

Ping: Definitely. Yes.

Andrew: Can I ask, over what time period would you expect to see a difference? So do we, you know, let’s say we do a baseline day zero, and then you instigate using Livaux…