Andrew: Yeah, beautiful. Beautiful place in the world. Okay. So, let’s dive in. I mean, this is just such a, it’s such a crucial topic, but it’s bigger than Ben Hur.

Dan: Yeah.

Andrew: So, you know, be nice to do it in one podcast, but I look forward to seeing you in more podcasts, to sort of delve in later, delve in further. So, let’s start with the foundations. And I guess, start with the bacteria. If we start with the keystone beneficial bacteria, why are they so crucial to human health?

Dan: Yeah, sure. So, excuse me. So, keystone bacteria are always something, Andrew, that we look at when we’re doing a gut microbiome profile, particularly on a new patient, and we’re trying to understand what the ecosystem is looking like at the foundation. The keystone bacteria, although they’ve got a relatively small abundance within that actual ecosystem, they have a pretty proportionately large influence, not only within the gut, but they sort of set the tone for how the whole microbiome behaves, if you like. And then they definitely extend over to other areas of health, like the metabolic side of things. So, it’s a really exciting area. And the testing that we utilize, pretty much regardless of which company is your preference, these days, actually zooms in quite well, I think, and gives us that really good understanding and snapshot, as practitioners, as to how that ecosystem looks. So, when we’re thinking about the terrain of the host and the short-chain fatty acid production in their keystone bacteria, we’re wondering, are they there to keep that gut lining intact, to lower inflammation, to then go on to produce beneficial compounds like butyrate, which we know help regulate metabolic health and regulate blood sugar, and protect against insulin resistance. And so, as I say, the effects are pretty wide-reaching, but when these keystone species, if you like, thrive, they tend to create a really nice, I guess, like, downstream ripple effect. So, the more harmful species within the gut, the pathobionts, they tend to lose their foothold. Digestion can improve from there, immunity becomes more regulated, and more intelligent, if you like. And the gut, I suppose, as a whole, just becomes more resilient under any sort of stress. And then, you know, in the opposite, when the keystone species decline, through, you know, means of poor diet or antibiotics or, what else, sleep disruption, stress, you name it, you know, the whole ecosystem tends to lose that stability. So, it’s kind of like the keystone species of the gut, they’re not just nice to have in there. It’s kind of like they’re the foundation of overall good gut integrity, immune tolerance, protection against allergy and autoimmune. And then, as I say, even now extending over to long-term metabolic health. So, pretty far wide and reaching, which is nice.

Andrew: Can I ask, with regards to, I guess not just keystone bacteria, but, you know, the “good guys,” seeing as, like, after, like, the first one to two years of life, our bacteria tends to be sort of imprinted, if you like, can you get, or have you seen, patients where you’re doing everything right, you’re feeding good polyphenols and good fiber, and still, you get this aberrant, or different set of bacteria being a hallmark, and something where we might go, “Oh, no. I want it to be different, but that’s them.” Do you ever see that? Like, it’s…

Dan: Where the results are sort of…

Andrew: Not textbook.

Dan: …just not what you’d expect. Not textbook…

Andrew: Yeah.

Dan: …not classic. Yes, yes. I mean, yeah, we do see that from time to time, and that’s where, you know, it pays to go over all those foundations, to check that they’re just not still receiving some sort of insult that you’re unaware of. Yep. Secondary to that, when you get thrown that sort of curveball, I always think about the bile acids as well, the primary bile acids, secondary bile acids, and whether there’s some other loop that’s inadvertently coming back in, and, you know, trying to, or not trying to, but offsetting whatever you’re doing. And although it’s well-intentioned, yeah, in those scenarios, that’s sometimes been the case, I’ve found.

Andrew: That’s such a great point. And, like, we…it’s really interesting how our focus can sometimes shift to looking at the gut, and forgetting that, well, you know, our liver plays an important role in this. Yeah.

Dan: Yeah, the good old enterohepatic recycling, you know, that term that gets thrown around a lot, but this is what we’re talking about, essentially, anything just getting spat back up through the liver and dumped back into the gut, and recycling. So, yeah, it pays to look at that, and that’s what I really love about some of these newer tests, is that they’re looking at stool omics, which is the, I guess the presence of primary bile acids and the presence of secondary bile acids, and I’m sure we’ll get into what they do and how that all works today. But as I always say to nearly every patient, it’s like, every year, the gut microbiome and what we know about it just keeps extending, you know. It blows you away.

Andrew: Evolving.

Dan: Five years ago, I wouldn’t have even been thinking about this stuff, or, 10 years ago, I wouldn’t have even known the names of some of these bacteria, what they do, so…

Andrew: No, that’s right. That’s exactly right. I mean, you know, back in the early days of my sort of career, it was, you know, lactobacillus acidophilus was the only one, and then this rhamnosus poked up. What?

Dan: Yeah.

Andrew: So, it was… Yeah, it’s evolved like you wouldn’t believe. Let’s talk about short-chain fatty acids, because that’s something that interests me as well, as, I guess, if we want to look at beneficial byproducts, does it matter how we get there as long as we get these short-chain fatty acids? So, I guess, let’s go into them, first. But let’s unpack them, which bacteria produce them, and some of the benefits that they deliver.

Dan: Yeah, sure. Yep. So, I mean, as far as I understand, there is a litany of them, but the three that we will see on stool reports, and what we most talk about, are the classic butyrate, acetate, and propionate. And these are like the currency of the microbiome. So, produced by these beneficial keystone species of the gut when they’ve got enough dietary input of fermentable fibers and resistant starches. But, you know, we’re even looking at roles outside of the gut now too, in terms of how they exert their effects. So, if we take butyrate, for example, which is kind of like, I always say, the VIP, you know, it’s like the rock star of the gut, we know that once that’s been produced endogenously in enough quantities, and utilized by the colonocytes, it then gets spilled over into the bloodstream, and can even travel up into the blood-brain barrier, and pass, and have a dampening effect on neuro-inflammation markers. So, again, that’s just another example of a few years back that would not have even been thought of being possible. So, again, whilst we’re, as I said earlier in the chat, we’re looking at the presence of keystone species, but are those keystone species being fed? And if they are, what’s the production capacity like of these short-chain fatty acids? And to your point, does it matter how you get there? Potentially, maybe not, because we do have butyrate, for example, as a supplement now. So, there are cases where a gut will be, for instance, really beat-up. That might be, you know, after an IBD flare, or a cocktail of antibiotics. And sometimes I’ll actually accelerate that, and rather than using the polyphenols and the prebiotics immediately, I’ll just stack a lot of butyrate into that gut, just to get inflammation down, so it can get to a position where it can then handle the fibers and the starches and whatnot.

Andrew: And do you find, as you were alluding to there, do you find there is sometimes a procession of what gets made first by a certain bacteria, and that might be setting up the foundations for the next bacteria to come along and take its place, and the next one and so on, so forth?

Dan: We do. We see that cross-feeding. So, it’s kind of like these guys pass the ball to one another, which is really interesting. And, you know, when they do that, it’s almost like then, the gut, the gut-brain axis, you could even argue that that’s then taking that information and passing it. So, it’s this big communication highway, that runs both ways, which is super fascinating. In terms of the individual species we’re thinking of, as far as butyrate goes, Faecalibacterium prausnitzii. And I have to say, I have a pet peeve, because a lot of practitioners still can’t pronounce that bloody species properly. Fecal bacterium, it’s Faecalibacterium. I just wanna make that clear, and go on the record. Faecalibacterium. Rant over. I’ll keep going.

Andrew: It’s like the old thing of firmicutes or firmicutes. We can…

Dan: Yes. I said that once recently at a talk. I looked at Brad Leech in the crowd. I said, “Brad, is it firmicutes…so, What is it? What is it?” It’s like tomato, tomato, you know?

Andrew: Well, I think we can get away from it now, because they’ve renamed, they’ve reclassified the whole clade, if you like, the whole taxa, as, what is it, Bacillota.

Dan: It’s probably a good thing.

Andrew: So… Stop the arguments over dinner.

Dan: That’s it. That’s it.

Andrew: So, feeding the bacteria. You mentioned that. Let’s go on this. I mean, this is a huge topic. Where to start? So, let’s start with a more pragmatic question, feeding too much. You know, the old days of using fructooligosaccharides, FOS, and 40% of your clients end up with massive amounts of wind, so we decided to look into different fibers, and polyphenols as well, that help beneficial bacteria, without those sort of adverse effects. Take us on this journey.

Dan: That’s a really interesting point. And because we… I think there’s a art in that too, Andrew, with, like, recognizing where your patient’s at, without necessarily months and months of data to study them. I mean, you get that later, through seeing them, inadvertently. But when you start out with them, the worst thing that can happen is you put them on a fermentable fiber that doesn’t agree with them. And they’re just gonna interpret that as “That naturopath made me feel worse. See you later,” you know. So, they’re, like I say, there is a bit of an art form to matching the fiber to the person, as well as their stage of progress with gut health. But, on that note, this is where I get really excited about the use of polyphenols, as opposed to actual fermentable fibers. One, sort of, that sticks out, that I use quite a bit, and actually has really good RCTs, human design trials, with really good results, is a pomegranate extract, called Pomella. And I think they, it was a 2023 study, off the top of my head, 14 participants, fed 250 milligrams of Pomella daily, for a total duration of about four weeks. And these were people in the group with really severely damaged gut biomes, so, you know, very much that mixed case of IBS-M, so, mixed constipation-diarrhea, SIBO, you name it. But intervening just with that one type of polyphenol was a really low-risk intervention, and what we actually seen was, there wasn’t an aggravation like you’d expect with some of those inulins and FOS and GOS and types of fibers.

But instead, we still seen an overall rise in the keystone species. We’ve seen rise particularly in Akkermansia and Bifidobacterium. No major shift in overall diversity. But the really cool thing about this study as well is they did look at Urolithin A production. So, this is that compound that our own resident biome will make, once it converts those ellagitannins from pomegranate. And that’s connected to a whole host of metabolic improvements. And I’m sure we’ll see, in coming years, that supplement hit the market, and it’s already starting to, in different parts of the world. But, if we can produce our own endogenous butyrates, and our own endogenous Urolithin As, then I think that’s obviously a better solution. But this is a really good example of something you can use in that really sensitive, inflamed type of almost SIBO-prone patient, where you’re concerned about fermentable fiber. And you can make some really good headway with that intervention just alone. So, often, I’ll actually say to patients, all we’re doing, apart from a few polyphenol adjustments in your diet for the next two consults, which might be six to eight weeks, is also get yourself a bag of pomegranate extract, and just add it to smoothies, daily. And I found that that lays really good groundwork. And from there, you can start almost on, like, a scale of least, you know, offensive, in terms of the fibers, and work them up, and just work out what’s their sweet spot. So, one you might sort of go to after that might be the guar gum, the partially hydrolyzed guar gum, at a low dose, and then scale it up. But I’ve had patients, you know, over the years that will come to me eating three or four foods only, you know. No fiber at all. Their gut inflamed and dysbiotic, and they just cannot tolerate it, all the way to be up to handling 10 grams of inulin, for example, months and months down the track, with a really diverse diet. So, the microbiome can shift, but you’ve just gotta get in there with the testing, and obviously, good clinical intake, and understand where they’re at, to match them to that intervention.

Andrew: And do you find that things like the polyphenols might be better suited to somebody who is a gas producer, or having a problem with wind because of that astringency to do with the polyphenols?

Dan: Oh, absolutely. And you often will find that in your IBS-D patient, you know, group that they will do better on that type of intervention, where you’re not asking for too much in the way of fermentable fiber, you know, to raise bacteria, but inadvertently, through a polyphenol, it’s happening, you know, and you are getting increased butyrate. So, theoretically, when the host conditions change like that, and some fermentable fiber then starts to come in and feed up those beneficial species, and they do produce more hydrogen sulfide, and more methane gas, by then you’d hope the lining of the gut is less sensitive, and can actually handle it and utilize it.

Andrew: You mentioned hydrogen sulfide then, and I… Help me here. I have a very dim, blurry memory of a paper once discussing that the mercapturic acid… [inaudible 00:15:16] but anyway, that it was sort of a… It was almost like your body trying to heal itself. But help…tell me if I’m right or wrong here, but it was a sort of, like, scrabbling for healing, and that it needed assistance. It was trying to do its job to protect you, but it was on its way out. So it was sort of like a canary in the coal mine. Is that where you’d go with, like, the hydrogen sulfide and things like that, to say, well, there’s something going on here, which I need to address?

Dan: When I see a high hydrogen sulfide-producing microbiome, that automatically raises alarm bells for, you know, you start to question is this… Okay, so, we’re seeing that down in the colon. Is that possibly happening upstream too, in the small bowel? And it’s the same, obviously, for methane. But these are sort of clues where you might say, all right, some more fermentable fiber right now might not be a good intervention strategy. Yeah, I’m not sure if that answers exactly what the example you gave, but…yeah.

Andrew: Yeah. All right. So, more on the polyphenols. What other…you know, we’ve spoken about… Oh, I know where I wanna go. I want to ask this. We tend to concentrate on these polyphenols and fibers for the gut.

Dan: Sure.

Andrew: But we sort of forget about that reflex action, if you like, not just for the lungs, which is the first one you’d think about, but also the genito-urinary system.

Dan: Ah, right. Right.

Andrew: Can we discuss this a bit? Because, like, I’m aware of, say, pomegranate with lactobacillus plantarum, certain species, certain strains. And I’ve got ellagic acid on the brain, but it’s not.

Dan: Yeah.

Andrew: But basically, helping to make, like, an antiseptic almost.

Dan: Yeah, that’s really interesting. And when you said genito-urinary, I straight away thought of cranberry extract, which is a polyphenol after all, as well. So, yeah, I mean, highlighting, if anything, that they’re…I mean, they’re antioxidants, at the end of the day. They’re, polyphenols, what are they? They’re the color on different fruits and plant matter and vegetables and fibers and whatnot. And we also sort of recognize them as generally good for health, for their antioxidant capacity. But it’s also a case that they’re working more in a deeper layer within the gut microbiome, and then potentially other areas of health, that maybe we don’t know as much about right now. But that reflex, that gut-lung reflex, or gut-liver reflex, that’s really exciting, and interesting.

Andrew: Cool. So, more about polyphenols. What do you tend to use? What and where and when? And take us through how you use these.

Dan: Look, as far as diet goes, I keep it really simple, Andrew. I say the five polyphenols. I say, but again, “Between now and next time I see you, all I want you doing is adding these polyphenols.” “Oh, what’s that, Dan? Is that boring?” “No, just hear me out.” “Cacao? Oh, great.” Yeah, because half of them already do it, you know. Blueberries, the pomegranate seed, even raw carrot, you know, and then green tea. So, I just say, pick those five, put them on your fridge, and I want you to do one of them every day, and you just rotate it.

Andrew: Right.

Dan: “Oh, sounds too simple.” And it’s like, “No, no. Just stick with me, and actually execute that, and I’ll see you in four weeks.”

Andrew: All right.

Dan: Yeah.

Andrew: Green tea. How do you take it?

Dan: Yeah. So, green tea, I mean, we can use it as a liquid extract, which is neat, you know, if we’re doing a herbal formula and we wanna sneak it in that way. And it’s obviously very, very concentrated. We can do it like that. Often, though, in the sensitive patient, I will often just say, you know, let’s just go tea bags for now. And I had a case the other week where I actually said to a guy, “Listen, where you would normally have that third coffee and fourth coffee for me, ditch that. Have your first and your second between, you know, 9 a.m. and 11 a.m.” And I said, “If you wanna have six cups for the remainder of the afternoon, of matcha or green tea, go for gold.” He just looked at me, he was like, “Aren’t I gonna be off my head with the caffeine?” I said, “Not necessarily. Look into L-theanine.”

Andrew: Yeah.

Dan: You know, this compound that comes in and kind of just suppresses the adrenergic response from caffeine. So, that’s often how I will sneak it in. Yeah. Through just tea bags, and then I’ll have patients that are already doing it with, say, matcha. Say, “Great. Keep doing it. Just make sure you’re using an organic form.” But yeah, polyphenols, I mean, I try and steer patients towards healing as much as I can with diet before we go in with supplements. And I probably sound like a broken record right now, but the amount of times I’ve used, there’s a brand that just does organic pomegranate peel extract. And it’s like, throw that in your smoothies, you know. A tablespoon, up to two tablespoons, even. But obviously, in new patients with really severe dysbiosis, we’re going in really low and slow, like one eighth of a teaspoon to start off with…

Andrew: Yeah.

Dan: …yeah, and building up.

Andrew: Yep. Yeah. I’ve learned that lesson too.

Dan: Yeah. Yes.

Andrew: What about the old adage. You know, we, in the olden days, we used to use bacteria, and you’d put it in, does a job, and never stays there. It goes out. Because of that, we spoke about it earlier, that bacterial imprinting, that sort of genetic imprinting, if you like. But now what we’re trying to do is feed the bacteria. Have you ever looked at using the polyphenols and the fibers, resistant starches, that sort of thing, to, as you mentioned, heal the terrain, so that any probiotic supplement that you give is going to have a longer-lasting effect? And have you been able to track that?

Dan: Well, that’s, I feel like that’s what we used to do before all these polyphenol extracts and prebiotics were available to us. I mean, you know, you could argue that you could do them with the diet. We didn’t know as much about them back then. So, we did have a lot more probiotics, you know, at our disposal. And you would remember as well as I did, in that 5, 10 years-ago space, there were so many probiotic cocktails, where it was, like, 12 to 15 different species. And I personally have moved a lot away from that approach. And I still do use probiotics, but I will often use single-strain probiotics only.

Andrew: Okay. Okay.

Dan: And I could count them on one hand. So, to your question, yeah, I definitely leverage the gut microbiome with polyphenols and prebiotics far and wide, more so than I do with probiotics. But I will use probiotics for their action, you know, for treating diarrhea in this case, or increasing motility in this case, improving mental health here, you know, reducing osteoporosis risk over here, you know, so, I use them single-strain in that sense. And there’s probably a couple of products that might combine one or two strains, or three strains max, but certainly, moving away from those big, you know, cocktails. I just never felt like they gave us measurable outcomes, and it was quite of a mixed bag, and a bit vague in terms of what they were doing. And a lot of those strains probably, now that we look back, did pass through, and do their thing on the way, which is cool. And we certainly now know that most probiotics don’t stick. Some do. But I just find you get better, more tangible results when you know what the probiotic’s doing firstly, you’re aware of the action of the strain, not just the species, and yeah, you’re thinking about that with regard to your follow-up sessions, and reporting back on their original presentation.

Andrew: Yeah. I like the way that you’re thinking, because I, like you, I was more of a shotgun…well, you know, we’re putting this bacteria into a cocktail of bacteria in your gut. What’s wrong with using a multi-strain probiotic, a multi-species probiotic? But I get where you’re going, is because you’re using mainly diet, mainly dietary or supplements, in that realm, and using the probiotic to just, as a linchpin.

Dan: Yep.

Andrew: Is that correct? Yeah?

Dan: Totally. Yeah, it’s like the icing on the cake, you know, that the probiotic, the foundations… We always say, you want your microbiome to produce all of these things itself. You want it to produce the short-chain fatty acids…

Andrew: Yes.

Dan: …the butyrate, the urolithin, you know, the postbiotics, you want your gut doing that. Because when it does do that, you don’t have to do…you know what it’s like when you get a patient and they come to you, and they’ve just done six months of antimicrobial treatment, with hardcore herbals. And there’s still a place for short-term use of that, but, you know, another good example is to 2′-Fucosyllactose. That compound is really exciting, and I’m using that quite a bit. So, that’s almost like the breast milk prebiotic, if you like.

Andrew: Yeah, yeah.

Dan: You know, and we know, with a lot of those studies, that the use of 2′-FL is getting the biome to a point to where it’s upregulating enough of those endogenous species to have its own antimicrobial effect, and have its, you know, permeability action, you know, anti-permeability action, itself. So, the gut’s doing the work itself, and moving away from the, you know, the blasting effects, if you like, of antimicrobials.

Andrew: Yeah, yeah, yeah. So, that sort of alludes to that procession thing that we spoke about earlier, although, albeit you’re fixing the terrain. Tell us about the 2′-FL, because, like, is there any condition that you think where it sings, like reflux? IBS? What? Anything?

Dan: You know what brings to mind, Andrew, is not so much a condition, but we do know that FUT2 non-secretors, so, people that don’t secrete the FUT2 gene, yep, so, they’re not able to utilize prebiotic, dietary prebiotics, as well. And so that is a really good…if you know that information, of course, and you’ve gotta have, you know, that situation where the patient has happened to have done genetic testing, and identified that they’re a FUT2 non-secretor. That’s where they won’t being able to produce their own 2′-FL, so giving them 2′-FL. And I’m thinking of an eczema case right now where we did that. We went in, after a certain point, did genetic testing, found out all of this information, and I put her on 2′-FL. And it was like, by the next consult, a massive corner-turn, visibly, you know. And she was ecstatic, and when I sent her the research about, you know, the FUT2 non-secretors and the 2′-FL, yeah, it was pretty interesting.

Andrew: It’s really interesting how medicine finally catches up to what naturopaths have been doing for decades. I recently read an article and it was saying, talking about the systemic influence on dermatological conditions, and it was like, really? Like, who would have thunk? Really? It’s like, catching up there.

Dan: Yeah. Yep.

Andrew: This was mainstream medicine. It was like, we’ve been doing it for decades,

Dan: It’s like when you hear them say intestinal permeability, or dare I say “leaky gut,” on TV. Oh, yeah. Yeah, we were onto that.

Andrew: Well, it’s really interesting. Like, I remember supporting a pharmacist who had a complaint raised against her, by a dietitian. And it’s because she used the word “leaky gut.” No, she used the word “leaky gut,” not syndrome. And it was serendipitous that that month, in “Nature” magazine, in “Nature” journal, and I’ll always remember it because it was weird. The picture was of a great white shark. I don’t know why, but that’s how I…

Dan: How it stuck in your mind. Yeah.

Andrew: That’s why it stuck in my mind. And so, I supported her with not just that, but the countless other articles, and it was just quashed.

Dan: Yeah.

Andrew: But it’s really interesting how we’ve turned the corner in mainstream medicine. “Oh, yeah, yeah, yeah. Sure. Yeah, sure.

Dan: Yeah. Yeah. It is interesting.

Andrew: We know about that.

Dan: That’s it. Yeah, yeah.

Andrew: Yeah.

Dan: I’ve found a few doctors, too, reaching out to say, “Hey, can you include me? Can you share that report you did recently, that gut test that I’m co-managing that client with?” And it’s like, “Yeah, sure, have a look. Don’t know how much of it you’re gonna be able to understand, but great, have a look.”

Andrew: Yeah. But I like the way that you’re backing up your clinical decisions with evidence, so that you can say, “I can show change…”

Dan: yeah.

Andrew: “…on a laboratory thing.” That, to me, is the, you know, it’s not just confidence. It’s we’re… Let’s call it confidence, in the profession advances.

Dan: Yeah, you need that backing. And that’s really helpful, not only in the medical space, but for a patient too. You know, you say, “We’re gonna test you when we first start, but have it in your mind that six months down the track, we’re gonna have a look at it again, and we’ll line up the two reports and we’ll show you,” you know, and yeah, the mental leap that you get when a patient confidently can see the changes, they can see the data, so then it goes away from just being subjective, like, am I imagining that I’m better from all of this stuff? And it’s like, no, no, your bifidobacterium is now threefold what it was when we started. Look at your short-chain fatty acids. Yeah.

Andrew: Yeah. Okay. So, not all fibers are created equal. We’ve spoken about a few here, but can you break down which fibers you use, where and when, covering resistant starches as well, to support, I guess, especially the keystone species, but the health of the patient? What have you seen?

Dan: I use, I have to say, more and more options these days. Again, like, I’m thinking back to maybe four, five years ago, it was, if I could get a patient on partially hydrolyzed guar gum, and then they’d stick on it and I could get them up to the 10 grams a day, I was cheering, you know. Now that we know a lot more about…and we just have a bit more confidence of, you know, using…when and where to use different things, like inulin, for example. Inulin was one, back in that time, that I rarely touched, you know, but I’m a lot more confident with these days. But there is still that hierarchy, where I’d put, you know, the polyphenol is in the first position, then the 2′-FLs, and, you know, guar gum, and then you start getting down the chain, into, which I’ll talk about, like, gold kiwi fruit extract, as well as, you know…what else have we got? You know, inulin, as I say, GOS, partially hydrolyzed guar gum, we ticked off as well. So, there’s that whole sort of combination.

And it depends on the presentation. So, like, I still do wanna say that there are patients that will, I’ll start off with, and based on what I can see, and maybe I’ve got the advantage that they’ve done a recent microbiome screen, so I can kind of look at that, and lever from there, and I can say, all right, I can confidently go in with, yeah, like, a gold kiwi fruit extract, for example, or a resistant starch type 2, from potato starch. These are the types of patients, usually, that are gonna have a depleted microbiome, with low butyrate, and low short-chain fatty acids, low Faecalibacterium. That’s the big clinical indicator I look for as well, particularly with those two aforementioned fibers. So, resistant starch type 2, I use an extract called Solnul. And then there’s that other one from the gold kiwi fruit extract. They can be really, really good for your IBS-C patients. It’s not to say that you can’t use them in IBS-D. You just wouldn’t go in initially with those.

Andrew: Hardcore.

Dan: Yeah, and hardcore, exactly. So, you’d look for a bit more terrain balance first, before you can start using it. But coming back to the guar gum, there’s been countless studies now where they will say, it kind of doesn’t matter where your patient falls in that IBS spectrum. It’ll have a stool-normalizing effect, so it’ll be great for diarrhea-prominent IBS, and conversely, constipation-predominant IBS as well. But as far as regulating the keystone species, linking it back to the original topics here, and increasing short-chain fatty acid production, lowering colonic inflammation, those are my favorites. I’m probably using less of, say, GOS and inulin these days, and more so focusing on those two I just mentioned, as well as the pomegranate and the 2′-FL. But I use all types. We’ve just gotta match the patient at the right time. And a really tricky one, I’ll just go into quickly, is, there’s a bit of a nuance with patients that will come in that will have constipation-predominant IBS, where that’s being caused by methane overgrowth, or it’s just plain old, you know…what’s a good example, you know, like a dietary fiber, or, you know, lack of movement, or lack of, you know, any other sort of influence that can create poor motility. But what I’m getting to is if it’s driven by methanogenic overgrowth, this is where we, say, if we do go in with inulin, for example, or resistant starch, we can actually worsen it. The methanogens can actually utilize that to their benefit, and grow further.

Andrew: Okay.

Dan: And, again, learned that one the hard way. We didn’t know as much back then. And it’s kind of like, “Hang on. Shouldn’t more fiber be better for these constipation patients?” and you’d see them get worse with more fiber. So, it’d just be that paradox. So I would say that’s probably 10%, maybe. Maybe, like, that 1 in 10, give or take, of IBS-C patients where you have to, you know, think of that and go, that’s why it’s good always to start with the testing with a new patient, because you can identify that straight off the bat, and go, “Okay, so we’ll withhold fibers for you in that case. Instead, we might work over here with this probiotic,” you know, L reuteri, for example.

Andrew: Right.

Dan: Yeah. Or a polyphenol.

Andrew: But, in those patients that get constipated with extra fiber, do you tend to sort of go back and look at the liver, about the bile acids and what’s going on there?

Dan: Totally. Hundred percent. Hundred percent. Yeah. Good point. And that’s where it comes back to those bile acids. And, you know, is it too much bile? Is it a high-fat diet, and the gallbladder’s working overtime, and there’s too much bile? Or is it poor motility because there’s not enough, you know, good bile, and therefore you start to question that pass-off of primary bile acids, being converted by the microbes, down to secondary bile acids. And by the way, that, if there is dysbiosis, that conversion happens very poorly. And so, what we often see then is signs of fat maldigestion, firstly, and poor motility. And on testing, it can reveal, usually, that you’ll see an overabundance of those primary bile acids, that are conjugated. And then it’s up to the microbes, as I say, to de-conjugate, to turn into those secondary bile acids. And the analogy I use there with patients is, like, think of an oil change on a car. That’s what we’re doing with you for this next little while. And I’ll use different compounds, stuff that we haven’t talked about yet, but I’ll use actual bile acids themselves like, TUDCA, for example. Ox bile.

Andrew: TUDCA?

Dan: TUDCA. Yeah, I won’t pronounce the acronym. It’s about this long.

Andrew: Oh, right. Okay.

Dan: But it’s a secondary bile acid.

Andrew: Gotcha. Right.

Dan: Yeah.

Andrew: TUDCA, I’ll have to look that one up. Don’t know that one. And what about when you might have an accessory condition? So, the one that’s springing to mind is something like a woman suffering anemia, suffering from anemia. So, excessive flow…

Dan: Yep.

Andrew: …for whatever. You’re trying to treat that. But what’s happening is the iron that she’s taking, we could talk about those here a lot with hepcidin, but we’ll go off track. But you’re trying to intercede in a positive way there, but while you’re doing it, the iron that she’s taking is causing all of these sort of keystone species and pathobionts, let’s say, to go out of whack…

Dan: Yeah.

Andrew: …and ending up with horrible wind. I mean, I’ve seen a case with hemorrhoids, for instance, where somebody was bleeding. So, it turned out that the, what I thought is the bacteria were basically living off the iron…

Dan: Using it, yeah.

Andrew: ..from the hemorrhoids. Yeah.

Dan: Yeah.

Andrew: And just using it. So, yeah. Tell us about that sort of thing, where you’re trying to intercede over here, but you need to do this, and it’s like, what do I do?

Dan: Yes.

Andrew: How do I juggle?

Dan: It’s so interesting you say it, because every symptom and condition you just listed, I feel like I’ve seen tenfold in, like, just the last few weeks. So it’s all fresh in my mind. But that can be really tricky, because that’s… Let’s take a case where that’s happening in a female that does have, like, you know, endometriosis or fibroids or something like that, and so there is that estrogen dominance. You know, and let’s just say, for example, they’re entering that perimenopause phase of life. So, this is an interesting point. At that transition, when the hormones start to change, bile regulation just goes topsy-turvy. So, we know from data that bile, which we need, obviously, for good hormone conversion, detoxification, and all of that hepatic stuff, starts to reduce in capacity. So, from that, we start to get more auto-intoxication, poor motility, you know. So everything sort of slows down during that perimenopause, and even andropause. It happens in both genders. So, yeah, that’s an interesting sort of position, where you’ve gotta flip back to, all right, we’ve gotta regulate the hormones, and go in with a lot more gall and bile support, and clean up the bile acids, give them that oil change, explain it to them like that. Yep.

And that’s where, you know, as I say, TUDCA, choleretics and colagogues, although we’ve gotta be careful with those in acute gallbladder situations and stuff like that, as well as even things like ox bile, to take the pressure off their own bile, you know, supplemental ox bile, to just help them digest and break down those fats, and clear hormones effectively. But yeah, you were mentioning iron in particular. That’s an interesting one too, because there is that whole concern about you give them the wrong form of iron, not only is it not getting digested and utilized, and increasing their levels, but it’s also creating dysbiosis at the same time. That dysbiosis is then gonna create more inflammation. That inflammation is then gonna go and feed back into, you know, the initial subset of symptoms. So, that can be really tricky. And that’s where, you know, once you’ve stabilized the hormonal flow, for example, in that situation, you might, obviously, look at the form of iron, and change the form of iron. But a good way that I like to do it clinically is using beef organs as supplements, because it’s kind of packaged. It’s iron-rich, obviously, but it’s packaged as, like, nature’s multi-mineral and multivitamin, if you like, and I feel like it’s got all the cofactors, and it’s a more gentle way of doing it. The only downside to that is you do need to do high doses.

Andrew: Yeah.

Dan: So, we’re talking four to six capsules a day, as opposed to, you know, one 24-milligram capsule of iron.

Andrew: Yeah. But you make a good point, because that, there’s that issue of too much iron, and you get, firstly, you get the excess iron not being absorbed by it, because you’re making hepcidin. There’s another thing that naturopaths have been doing for decades, or over a decade, and medicine has only just caught up in the last two, three, four years. And now it’s guidelines. It’s like, wow.

Dan: Yes.

Andrew: But yeah, you might have to use higher dose of something else, because the iron is in a lesser dosage within that thing. But is that bad? Probably not.

Dan: That’s right. Yeah.

Andrew: Unless they’re, you know, critically low in iron, in which case you might look at other forms of administration.

Dan: And it’s tricky to explain that one too, because… I’m using a broad stroke here, but again, I’m thinking of a recent case where the patient said, “But Dan, the doctor’s saying I need 100 milligrams per day in supplemental form, and this little 24-milligram thing won’t do. It won’t touch the sides.” You know, and that’s where you need to say to them, “Well, actually, the research is changing,” to your point, “and saying that lower doses, less frequently, to avoid hepcidin,” yeah, “are more clinically effective,” but, yet, you’ll still see, in every pharmacy…

Andrew: Oh, yeah.

Dan: …100 milligrams of ferrous fumarate or whatever, you know, very pro-constipation. Exactly. Yeah. So…

Andrew: Yeah, 108 milligrams.

Dan: It’s an ongoing battle. Yeah.

Andrew: Oh, yeah. Ah, now, I was also gonna… There was something else I was gonna ask you. Oh, that’s right. What you were alluding to before, and for our listeners out there, please forgive me for this. I’m going to use an acronym that I learned way back in nursing, and it’s going to cause offense.

Dan: Can I guess what it is, Andrew?

Andrew: With regards to gallstones. What is it?

Dan: Oh, and it’s probably not, but I thought you were going for your old segmented filamentous bacteria.

Andrew: I was going to kindly leave that topic out, but…unless you wanted to cover it. So, the acronym is to do with gallstones, and it was one, and please forgive me for this. It’s just, but it’s sort of fat-shaming, but the acronym was “The five Fs of gallstones.” So, it was like fat, 40, female, fertile, flatulent. And I was alluding that back to when you were talking about the, when women enter the perimenopause, all of their, not just metabolism, their hormones, but also their bile acids decrease. And it just feeds into this whole issue of creating a seed for a gallstone to start to be created. Interesting

Dan: Yeah. And this is why we see more gallectomies is the term, I think. Gallbladder surgeries, essentially, post-menopause.

Andrew: Yeah. Yeah, yeah.

Dan: Probably likely due to that, or largely due to that, that lack of bile.

Andrew: It’s really, really interesting, what I’m seeing is it’s a lot more younger people. I never used to see them. It’s real interesting.

Dan: Yes. Yes. Yep, well… Yeah. We can go on about that all day, with Western diet and…

Andrew: Yes.

Dan: …microbiome shifts.

Andrew: Another podcast.

Dan: Another podcast.

Andrew: Okay. So, what else do we need to learn? You’ve alluded to, you know, obviously, diet, but sleep, for instance. Sleep is such a pervasive issue. Trying to get good, restful sleep is such a…something that eludes most of us. Tell us about how important it is, and what effect you get from correcting poor sleep patterns into a good night’s restful sleep.

Dan: I mean, there’s, my brain shoots straight off into the, you know, four or five different things, but the primary one I think about is melatonin. So, if we’re not sleeping much, we’re not producing as much melatonin. So we could argue, you know, a poor production of melatonin, small melatonin pool, there’s just less systemic anti-inflammatory benefit going around. So, less signaling down to the gut, less Treg production, T regulatory cells. And we know, obviously, from studies of shift workers and stuff like that, that that altered circadian rhythm disruption has a massive impact, again, linking back to keystone species. So, keystone species will drop very, very quickly under that. And if you take that circadian rhythm disruption, you link it with high stress, processed diet, the wrong types of fats, and alcohol, you’ve got a quick recipe for, you know, a very angry gut, a very inflamed and angry gut, which, by the way, isn’t necessarily going to manifest as a digestive problem for some people. For some it will, absolutely. They’ll feel it straight away. “My gut is not good when I do shift work.” It’s noticeably different the next day. And others, it might just be all mood. Or memory and cognitive deficits, for example. And I think that comes down to genetics…

Andrew: Yeah. Yeah.

Dan: …where it plays out.

Andrew: That’s really interesting. That’s a really interesting point. So, would you help these people to start to get a good night’s sleep with, like, using just beautiful, gentle, and might I say, good-tasting things like L-theanine, and things like that, so that you can just really, not ram them in a certain way, but nudge them in a certain direction?

Dan: Well, there happens to be a product that I’m using a lot personally lately, and in clinic, and it’s literally L-theanine and kava, which I just, I said…

Andrew: Right.

Dan: I said, “thank you.” Two ingredients, firstly. Simple. It’s chewable. Great. You know? So, yeah, kava, I love the use of kava. L-theanine, definitely. And by the way, I use that for sleep, but I also use it through the day, for patients that they’re under a lot of stress. And it comes back to vagal tone as well. You know, if the vagus nerve’s upset and angry, the nervous system’s just never getting that proper grounding, and parasympathetic release.

Andrew: Yeah.

Dan: And, yeah, I mean, we know this, just like we know Tuesday comes after Monday, but so many of our patients that are stressed are gonna be just in sympathetic dominance, and all the flow-on from that. So, yeah, a massive, just highlighting that link between the nervous system and the environment, and stress perception with the gut, the gut taxa. So, we know that that’s very, very, you know, prone to create that dysbiosis.

Andrew: Can I just ask, with regards to these, and I’m gonna say they’re mostly women, they’re doing everything for everybody else, but they’re go, go, go. They’re the fine silk iris women, they’re warrior women, you know. They’re always on the go, but they will not slow down. And they eventually start to, you see this arc, a descending arc of their energy, and hormones are changing and things like that. Can you change them? I’ve never been able to change these type of women. I have tried to get them to walk along beaches with their husband and the dog and things like that. But their base routine never changes.

Dan: There is a portion of people we can’t change, for sure. And, you know, sometimes you have to have those hard conversations, where it’s like, you know, either this stuff isn’t for you, or it’s not the right time, you know? It’s rare, but yeah, definitely. And men as well. In fact, probably more men than women.

Andrew: You do? Okay.

Dan: But to that sort of, you know, archetype of patient, obviously, once the peri, you know, hits in, and then full-blown menopause, there’s such a critical place for hormones. And I say this openly. I’m not against hormone replacement therapy done right. Done wrong can be terrible, you know. But done right, with the right doctor, and with the right guidance, I’m all for it. Because if you get that baseline corrected, you know, and you stabilize things, they’re gonna feel everything else we’re giving them a lot more, and they’re gonna see the benefit of it a lot more. But it’s hard to appreciate all of those things you’re doing when there’s just a plain old deficit of progesterone and DHEA, testosterone, you know. And estrogen. Yeah.

Andrew: I love your work. Can I ask, as a final question, this is gonna be a piece of string, right? It’s basically to recap what we’ve spoken about today. So, which sort of things would you go first as a generality? Would it be polyphenols, and then fibers, and then bacteria? I know that you’ve been speaking about fit the patient. I get that. But what would be your generalized go-tos be?

Dan: I start with diet. So, we have to start with the diet, and get some leverage there. It’s tricky to say, Andrew, because I often think of a lot of patients where I do use a combination of all of these things, where we might combine two or three of them. And again, I’ve said it already, but an example might be the pomegranate extract, the golden kiwi fruit extract, and the resistant starch. Yep. So, it’s a combination of things. And the way I work is, gut is a big part of what I do, but there’s also a lot of other interventions that I do as well. So it can be a little bit tricky to say, you know, what I do mostly, or what I see, you know, gives us the most bang for buck. But I will say that most patients, I’d say 9 out of 10 of my patients, regardless of what they come in for, will start with stool metagenomics.

Andrew: Right.

Dan: Straight off the bat. Yep.

Andrew: Gotcha.

Dan: And that one is hard to rationalize sometimes, A, because it’s expensive. And if a patient’s coming in and saying, “But I don’t have any gut symptoms,” but I’ve got all this going over here, to convince them that we still need to look in the gut, because we’re gonna get our most purchase on that, is tricky sometimes. But as I say, it’d be probably a good 90% of patients will do a baseline stool work-up, and work off that. And a big area that springs to mind is metabolic health, you know. So, where one patient might go straight in with the berberines, the myo-inositols, the seleniums, or whatever it might be, I still do all that. But it’s gonna be very, very gut and bile acid, you know, and hepatics involved, with weight loss and metabolic health in particular, to start with. And then, obviously, gut cases, where we’re going in with those as no-brainers. So, I don’t know if I answered your question, but…

Andrew: No, no. You did. But I said this is gonna be my last question, but it isn’t.

Dan: Keep them comin’.

Andrew: I’m gonna have you online for four hours. So, can I ask, then, you mentioned berberine there, and this is something that still commonly comes up. If, let’s say, a woman is using berberine and myo-inositol for polycystic ovarian health, how do you balance that, using berberine as a longer-term supplement with aberrations in keystone species, like Akkermansia? And a secondary question, sorry to follow on here, is, is there a case where, let’s say, too much Akkermansia, or Faecalibacterium prausnitzii, might be detrimental?

Dan: Yeah. I don’t know as much about an overabundance of Faecalibacterium, probably, honestly, Andrew, because I’m used to just seeing it low, if anything.

Andrew: Mm-hmm. Yep.

Dan: I’m used to seeing that, you know. Akkermansia, sure, I’ve seen that high in multiple sclerosis, many times. Yep. And being a mucusoa end feeder, we’ve gotta strike the balance of Akkermansia. So, too little, no good. Too much, no good. We need that sweet spot, where the turnover is, you know, adequate, and there’s enough protection from that lining. So, and the first part of the question, with the berberine, you know, I think a good intervention to do alongside that, coming back to that’s where you might use supplemental butyrate, to guard against that.

Andrew: Right.

Dan: No? Yeah.

Andrew: Gotcha.

Dan: It’s knocking out those keystone species, potentially, so we’re gonna see short-chain fatty acids drop. So, you’re still giving the colonocytes direct fuel. Yep. And we’re offsetting…and again, like, if you can, and if the patient is going to tolerate it, in a prebiotic fiber in there as well, just to keep some feeding going on as you’re knocking them out, or there’s some collateral damage. With berberine, though, I do, always, regardless, cycle it. So, we might do three months on, one month off. You know, or two months on, two months off. Yeah.

Andrew: I love your work. I love your mind, how you’ve always got the patient’s health in the foremost, but you’re working around, trying to juggle things, to suit how best to intervene, while getting, obviously, the gut hallmark, and, you know, these keystone bacteria that we’ve spoken about, but you’re working around it, to sort of make it not just pragmatic, but also beneficial in the long term. I love your mind.

Dan: Oh, cheers. I appreciate that. And I think it’s, this is where, you know, a classic example of how what we do has to be scientific, because I have to keep those things in mind as I’m sitting there talking to the patient in simple terms. I have to be thinking about these keystone species, and what their, you know, butyrate production is like, and, you know, what tools are gonna best match them. So, it’s a cool space to be in, and I like that we can do the before-and-after testing, and clinically validate what we’re doing as well, so it’s not just all guesswork.

Andrew: Love your mind. Dan Sipple, thank you so much for joining us today on “Wellness by Designs.” Brilliant speaking with you.

Dan: Pleasure. Good on you, mate. Cheers.

Andrew: And thank you, everyone, for joining us today. Remember, you can catch up on the show notes for this. We’re gonna be putting up a heck of a lot in here, but also the other podcasts, on the Designs for Health website. I’m Andrew Whitfield-Book. This is “Wellness by Designs.”