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Intestinal Inflammation: Clinical Definition, Testing and Treatment with Dr. Brad Leech and Lisa Costa-Bir

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Intestinal Inflammation: Clinical Definition, Testing & Treatment w/ Dr. Brad Leech & Lisa Costa-Bir

Join Dr. Brad Leech and ambassador Lisa Costa-Bir on her inaugural podcast on all things Gut Inflammation. Brad breaks down the importance of functional testing for assessing inflammation, with a detailed discussion on interpreting the four major tests: calprotectin, lactoferrin, occult blood and Secretory IgA. Learn about the importance of personalising treatment for patients with gut inflammation and how to effectively use (and dose) key anti-inflammatory herbs and nutrients for optimal efficacy.  Clinical take-homes for use in your practice will also include dietary recommendations and an interesting discussion on colon cleansing!    

Covered in this episode

[00:50] Welcoming Dr. Brad Leech
[02:02] Intestinal inflammation vs intestinal permeability
[03:39] Signs and symptoms of intestinal inflammation
[06:40] Functional assessments for intestinal inflammation: calprotectin, lactoferrin, faecal occult blood, and secretory IgA
[23:23] How the microbiome influences intestinal inflammation
[34:01] When should we test our patients?
[38:07] When to refer
[40:07] Treatment options for combating intestinal inflammation: curcumin, omega-3s, GOS
[44:32] Which diets improve intestinal inflammation and why?
[46:50] Colon cleansing: do or don’t?
[49:48] Thanking Brad and key takeaways

Key takeaways 

  • Intestinal inflammation is a response from injury due to stimuli resulting in intestinal inflammation anywhere along the GI tract. Inflammatory mediators interleukins, cytokines, and prostaglandins are released resulting in cellular dysfunction. 
  • GI tract Si and Sx of intestinal inflammation include:
    • bloating
    • abdominal pain
    • cramping
    • diarrhoea
    • changes in bowel movements
    • excess flatulence
    • urgency
    • blood or mucus in stools
    • mouth ulcers
    • nausea
    • reduced appetite 
  • Systemic Si and Sx of intestinal inflammation include:
    • fatigue
    • weight loss
    • fever
    • anaemia  
  • Four key functional markers of intestinal inflammation:  
    • Faecal calprotectin 
      • A cheap, stable and efficient functional test to help determine acute inflammation, and can assist in differentiating between IBD and IBS.
      • A person with IBD will present with >150 faecal calprotectin whereas IBS patients rarely have high calprotectin.
      • Calprotectin is also a good tracking marker to assess patient’s risk of relapse. Also associated with autoimmune conditions. 
      • NSAIDS drastically impact increased levels of faecal calprotectin.
    • Lactoferrin 
      • Measures inflammation produced from neutrophils.
      • Can indicator IBD activity (high when there’s high disease activity) and useful for predicting relapse.
      • Most useful for assessing treatment efficacy. 
    • Faecal occult blood 
      • Highly researched and accurate marker.
      • Indicates damage to the GIT.
      • Presence of occult blood associated with increased risk of colorectal cancer
      • Positive results for occult blood without any diagnosis requires referral for further investigations.
      • Useful for identifying IBD.  
    • Secretory IgA 
      • Request stool S IgA as the preferred assessing intestinal S IgA (not saliva!).
      • Assess alongside calprotectin.
      • High S IgA correlates with IBS type D, lupus, intestinal permeability.
      • Low S IgA associated with glucose metabolism disorders 
  • Testing every 6 to 12 months helps to monitor for risk of relapse, improvements, and treatment efficacy. 
  • Levels of these markers are usually inconsistent in infants due to developmental processes and lacking research in developing reference ranging for this population. 
  • Ulcerative colitis and Crohns disease commonly present together due to their autoimmune nature and the risk of developing multiple GIT issues can be reduced by addressing aggravating factors and inflammation. 
  • Microbiome meta-genomics allows us to test for the 6000 commonly present species in the human gut (out of a possible 28,000) of which healthy populations will have 150-200 species present. 
  • Understanding that there are a diverse range of metabolites being produced helps clinicians assess the overall pro or anti inflammatory landscape. Linking species to the metabolites being produced such as the LPS family or SCFA’s can help us conclude what aspects of the microbiome we need to treat. 
  • Hexa-LPS: a marker of intestinal inflammation released by activation of immune receptors from bacterial interactions. This particular subgroup of LPS is highly proinflammatory. 
  • Fungal presence in the gut is relative to the overall microbial environment and therefore gut health. A healthy gut microbiome regulates fungal overgrowth and reduces risk of intestinal inflammation. 
  • When to refer:
    • High lactoferrin without any diagnosis 
    • Calprotectin >200 
    • Occult blood without diagnosis 
  • Treatments include:  
    • Anti-inflamatory agents such as curcumin, S. boulardi, fish oil, and aloe vera 
    • For Hexa-LPS reduction: Start slow and titrate up to 3/g daily GOS for five weeks.  
    • Dietary components: reduce saturated fats and increase omega 3’s. Remove suspected food sensitivities. 
    • Colon cleansing and enemas WILL change the gut microbiome and can be beneficial in some cases, however the risk is becoming dependant on them and the underlying causes aren’t being addressed.

Resources Discussed and Further Reading

Dr. Brad Leech

Dr. Brad Leech's website
Learn more about the microbiome with Co-Biome
Brad’s courses for practitioners
Brad's Brainiacs Facebook mentoring group
Clinical Mastery - Increased Intestinal Permeability with Brad Leech
Research: ‘The Subjective Well-being and Health-Related Quality of Life of Australian Adults with Increased Intestinal Permeability and Associations with Treatment Interventions.’ J Altern Complement Med, 2021
Research: ‘Risk factors associated with intestinal permeability in an adult population: A systematic review’ Int J Clin Pract, 2019
Research: ‘Treatment Interventions for the Management of Intestinal Permeability: A Cross-Sectional Survey of Complementary and Integrative Medicine Practitioners.’ J Altern Complement Med, 2019

Faecal Calprotectin

Research: 'A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy.' Gastroenterology. 2005

Faecal Lactoferrin 

Research: ‘Fecal lactoferrin accurately reflects mucosal inflammation in inflammatory bowel disease.’ World J Gastrointest Pathophysiol, 2019

Secretory IgA 

Research: ‘Secretory IgA in Intestinal Mucosal Secretions as an Adaptive Barrier against Microbial Cells.’ Int J Mol Sci., 2020

Fungus and Intestinal Inflammation

Research: ‘Fungal Dysbiosis and Intestinal Inflammation in Children with Beta-Cell Autoimmunity.’ Front. Immunol., 2020

Curcumin and Intestinal Inflammation

Research: ‘Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection.’ Int J Mol Sci. 2019
Research: ‘Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin.’  Nutrients, 2020

Omega 3’s and Intestinal Inflammation

Research: ‘Omega Fatty Acids and Inflammatory Bowel Diseases: An Overview.’ Int J Mol Sci. 2019
Research: ‘Impact of Omega-3 Fatty Acids on the Gut Microbiota.’ Int. J. Mol. Sci. 2017


Lisa: Hi. I'm Lisa Costa Bir, and welcome to FX Medicine, where we bring you the latest in evidence-based integrative, functional, and complementary medicine. 

FX Medicine acknowledges the traditional custodians of country throughout Australia where we live and work, and their connections to land, sea, and community. We pay our respect to their elders, past and present, and extend that respect to all Aboriginal and Torres Strait Islander peoples today. 

Joining us on the line today is Dr. Brad Leech, an internationally recognised integrative medicine practitioner. Brad has taught and developed subjects in the fields of integrative gastroenterology, naturopathic medicine, nutritional and dietetic medicine, and public health. Brad is also the lead clinical educator and co-creator of Co-Biome. In addition to being a researcher and working with patients, Brad offers practitioner support through his mentoring program, Brad's Brainiacs. He's also just completed his PhD developing a guideline for intestinal permeability. 

Hi, Brad. It's great to have you here today.

Brad: Lisa, it's fantastic to be chatting with you on this podcast.

Lisa: I'm really excited to have you on too. 

So, today, I really wanted to focus on intestinal inflammation with you, as you're an expert in this area, and it's an underlying driver of so many of the conditions that we see in clinic that are not limited to the gut. And I feel like intestinal permeability gets a lot of discussion, but intestinal inflammation, not so much. So, I'm excited to talk about what intestinal inflammation is, how we can use tests as clinicians to then best-inform our clinical practice. So, I guess my first question for you is, when we're talking about intestinal inflammation, what are we talking about when we use that term? How is it different from intestinal permeability?

Brad: Sometimes it's best to start actually just defining what is intestinal inflammation. So, intestinal inflammation, it's a complex biological response to injury as a result of stimuli such as pathogens, damage to cells, or even irritants. And it involves inflammation anywhere within the gastrointestinal system, from mouth all the way to anus. In technical terms, intestinal inflammation involves an increased reduction of inflammatory interleukins, cytokines, and prostaglandins. Now, this causes intestinal cells to become inflamed, and as a result, they don't actually function how they should. The last thing I'll probably mention here is that inflammation can be acute in patients with, let's say, inflammatory bowel disease going through a flare, or low grade in patients with mild gastrointestinal symptoms.

Lisa: I'm really interested that you said that it can occur right from the top in the oral microbiome or the oral cavity. So, could we be looking at someone's tongue and saying yes or no with regards to intestinal inflammation?

Brad: Oh, that's a great question. My research hat says there is no peer reviewed research to confirm that. But my traditional Aveda hat says, "Oh, yes, it's a rule of three." If there's three things that can indicate that there is inflammation, then there possibly is. But we’ve now come to a point in, let's say, technology and understanding that we've actually got a lot of very validated methods. And sometimes we don't necessarily just need to rely on clinical symptoms.

Lisa: So, what symptoms could a client have that might point us to the fact that they have intestinal inflammation if we can't actually see the intestines?

Brad: There's a number of symptoms, both within the gastrointestinal tract, but then also systemically. So, some of these gastrointestinal symptoms could be as simple as bloating, abdominal pain, diarrhoea, cramping. Patients might even present with a change in bowel habits, constipation. They may report excessive flatulence and urgency to go to the bathroom. I have patients saying, "I'm cautious from going outside because I might need a bathroom at a drop of a hatch." You might even have blood or mucus in the stool. 

Interesting you mentioned tongue. A clinical symptom could even be mouth ulcers. So, if there's mouth ulcers, could be indicating that there's some form of intestinal inflammation. Other things like nausea, reduced appetite are some of the main gastrointestinal symptoms. But someone with intestinal inflammation or someone where you'd want to assess them for intestinal inflammation may also present with fatigue, weight loss, fever, and even anaemia, just to name a few.

Lisa: Yes. Okay, wow. So, there's quite an extensive list there. Do you think a client could be asymptomatic and still have intestinal inflammation?

Brad: They could be heading down that avenue of developing intestinal inflammation. But from my experience, if someone actually has quite acute or measurable intestinal inflammation, there will actually be some form of clinical sign or other related health conditions that they may be presenting with.

Lisa: Okay. And I guess from a clinician's perspective, we can often say, "Oh, well, they would be symptomatic, it's just the client may not actually realise that these are symptoms of intestinal inflammation." Right? Because I have clients that have low ion or IBS symptoms and they don't necessarily consider those to be manifestations of intestinal inflammation.

Brad: No, that's 100% right. We've go to look at the whole patient when we consider whether or not we should be assessing them or evaluating them for intestinal inflammation.

Lisa: So, how would you generally assess someone for intestinal inflammation?

Brad: So, there are multiple different markers that we can use to evaluate someone for intestinal inflammation. Now, from my clinical experience and from what I've been reading in the literature, there's four main, let's say, functional markers. And these are calprotectin, lactoferrin, occult blood, and secretory IgA. Would you like me to discuss these in a little more depth?

Lisa: I would love you to, yes.

Brad: All right. Hold on to your horses.

Lisa: Which one are you going to start off with?

Brad: We'll start off with calprotectin.

Lisa: Okay.

Brad: So, calprotectin, it is well-researched and a very validated marker for intestinal inflammation. From a very practical point of view, faecal calprotectin, it's cheap, it's fast. It's patient-friendly. We don't need to go and prescribe an endoscopic procedure to evaluate intestinal inflammation, we can do a very simple stool test. Now, the other beauty thing about calprotectin is, it's stable for about a week at room temperature, meaning that we can get it to the lab and get a very accurate result in a very timely manner.

Lisa: Wow.

Brad: Now, calprotectin, it's a marker for acute inflammation, and it can actually establish the degree of gastrointestinal inflammation. It can be used to monitor inflammatory bowel disease, and most importantly, can actually differentiate between IBD and IBS. 

So, we've got organic gastrointestinal disorders, and we've also got functional gastrointestinal disorders. Organic as, of course, are your inflammatory bowel disease such as Crohn's disease, ulcerative colitis, colon cancers, and so forth. And then you've got your functional bowel disease such as IBS. Now, if somebody has an elevated level of faecal calprotectin, generally above 100-150, then you'd be more thinking, "Well, this patient actually has an inflammatory bowel disease or an organic-based reason to explain this elevation." It's very rare to have a patient with IBS that has high calprotectin.

Lisa: Okay.

Brad: So, calprotectin can be used to identify patients at risk of relapse with the research actually showing that patients that are asymptomatic with inflammatory bowel disease, so they've already had their diagnosis, but they're managing it quite well with a nutritionist or a naturopath. If they have a high calprotectin level, then there's an 80% chance that they're actually going to relapse in the next six months.

Lisa: Oh, my goodness.

Brad: So, actually testing on a regular basis means, as a clinician, I can go, "Oh, this patient's at risk of a relapse. Let's start our relapse prevention protocol now to actually prevent them going down that avenue." Something to note here is that faecal calprotectin is better correlated with relapses of ulcerative colitis compared with relapses with Crohn's disease. So, it will be high in Crohn's disease, but it's more indicative of ulcerative colitis.

Lisa: Okay. That's really interesting. Because I've got a patient, she thinks she's got both. She's been diagnosed with actually both, which I didn't know could happen, but apparently, it's a thing.

Brad: It is quite common to actually have both ulcerative colitis and Crohn's disease. I put this down to, as they're both autoimmune disease, and we know the stats of once you develop one autoimmune disease, you are three times more likely to develop another one unless you're actually addressing the risk factors for autoimmune disease, which are your intestinal permeability, your inflammation, your immune dysregulation, and your dysbiosis. So, it's so common to have this clustering effect. I had a patient just the other day that had seven autoimmune conditions.

Lisa: Oh, my goodness.

Brad: And it comes down to, well, they're not actually addressing the cause, they're just addressing those individual autoimmune conditions.

Lisa: Oh, it's one of my favourite topics.

Brad: So, faecal calprotectin, it's very useful in autoimmune conditions. It's also elevated in things like lupus, celiac disease, ankylosing spondylitis. But it can also be high in a number of other conditions such as acute bacterial diarrhoea. Okay? And it can actually distinguish whether or not someone has acute bacterial diarrhoea verse viral diarrhoea.

Lisa: Okay.

Brad: The other one to mention here is medication. Now, I'm sure you know what medication I'm going to mention here...

Lisa: I don't.

Brad: But there was a recent study with 40 healthy individuals. And it actually showed that 75% of these individuals, they had no health conditions. But after taking NSAIDs for two weeks, 75% of them developed elevated faecal calprotectin.

Lisa: Oh, my gosh.

Brad: Yes. Wow. So, it's a very useful marker to evaluate intestinal inflammation. And another, let's say, as useful marker, would be lactoferrin. So, less known, but still, it's got a lot of very similar characteristics to calprotectin. So, both are produced from neutrophils in the intestines, and both indicate inflammation. However, lactoferrin is more indicative of things like inflammatory bowel disease activity. So, rather than just predicting relapse, it can actually determine the activity of the inflammatory bowel disease. It can be used to also predict relapse. But this is the one that I really like, is that it can be used in clinical practice to see how treatment is going.

So, the thing lactoferrin is it's not like a marker, like secretory IgA, where we're trying to either increase it or decrease it, it's almost a biomarker where it's like, okay, this is indicating that there's inflammation. We don't necessarily want to target the lactoferrin, we actually want to take a step back and go, "Well, lactoferrin will be high when there's high disease activity," and we'll actually want to treat the patient's disease or underlying condition to bring down the disease activity. And then what you'll find is the lactoferrin will actually come down.

Lisa: So treating the cause and just using it as a biomarker for disease activity?

Brad: Exactly. Exactly. So, if someone actually has high lactoferrin, then they're more likely to have high calprotectin too. Yet, if someone has high calprotectin, they won't necessarily have high lactoferrin. So, it's one of these interesting ones. So, really, if someone has both these markers of inflammation high, then, first and foremost, you're thinking inflammatory bowel disease. But if only lactoferrin was high, yes, you'd be thinking inflammatory bowel disease, but you could also be thinking things like a C. diff infection as well. So, these markers for intestinal inflammation, they provide a lot of information. But there's others that are, let's say, a little less research that might actually give us some indication as to why there is inflammation. And these include the faecal occult blood and secretory IgA.

So, firstly, the faecal occult blood, it's well-known, and it has so much research. When I first started diving into this topic, I was almost blown away because there was systematic reviews of of systematic reviews of occult blood, which is the highest level of evidence. And there's so much research that I humanly could not read all the research on occult blood. But if you read the meta-analysis, you get a good understanding of how it can be used in clinical practice.

Now, most patients over the age of 50 will actually be well aware of this test already because it's the test that the government will actually send out to do a screening for bowel cancer. The presence of faecal occult blood in the stool, it's associated with gastrointestinal disorders and indicates that there is damage, aka, inflammation, somewhere within the gastrointestinal tract. Now, a positive occult blood is predictive of an increased risk of colorectal cancers, hence, why the government will utilise this as a screening.

The beauty here is if we can actually identify this early, then there's a significant reduction in the risk of serious colorectal cancers if we can actually find it early. Apart from colorectal cancers, it can also be used to identify inflammatory bowel disease. And what I find interesting from a clinician's perspective is if somebody has ulcerative colitis and it comes back negative, it can actually indicate that there's mucosal healing happening, which is a great way to evaluate how treatment is going.

Lisa: Wow. I'd never thought about it like that.

Brad: Unfortunately, there isn't a scale for faecal occult blood. It's, you're either positive or negative. So, when we measure occult blood in a lab, the process is actually very similar to a COVID RAT test. Okay? So, what you'll do is you'll dip a stick into the sample and you'll mix it up with a solution, and then you'll add three drops into the test, and then two or one line will appear. Now, if there's one line, it's negative. If there's two lines, it's positive. It's very simple, but very accurate. And so it can actually indicate, well, yes, this person does or doesn't have occult blood in the stool. 

Something I really want to stress here is, if a patient has a positive result and the cause is unknown, so they don't have inflammatory bowel disease or they don't know that they have colorectal cancer, then we need to refer, and we need to refer immediately because we need to do further investigation. We need to understand, well, what is happening here?

Lisa: Absolutely. And this would occur, I'm guessing, if the patient has done the test through us, they've done a CDSA or something like that, right?

Brad: Yes, if they've done any good quality gut test, generally, they will measure for occult blood. And if it's positive, we really need to go, "Okay, let's refer in this instance if we don't know what the cause is."

Lisa: Absolutely.

Brad: And that generally involves a letter to their primary healthcare professional to say, "X patient has done this test and it has come back positive for occult blood. Further testing is required." They might do calprotectin, they might do an endoscopy or a colonoscopy. It really depends on their clinical symptoms.

Lisa: Sure.

Brad: The last, let's say, functional test that I'll use in clinical practice is secretory IgA. And I really feel that this is a test that a lot of naturopaths and nutritionists are utilising in clinical practice. I'm almost going to break a few hearts here, but there's actually a lot of misconception when it comes around to secretory IgA. You see a lot of the research, when you go into PubMed and other research databases and you search for secretory IgA, the vast majority of the research is actually done on saliva.

Lisa: I was going to ask you.

Brad: Secretory IgA?

Lisa: Mm-hmm.

Brad: Yes.

Lisa: So, we need to be asking for stool.

Brad: Stool. We need to ensure because, unfortunately, there isn't any study to confirm that salivary secretory IgA correlates with stool secretory IgA. So, we really need to rely on stool-based studies. The other caveat here is a lot of the stool-based studies are actually done in infants. And we know from things like zonulin and calprotectin, especially in that first couple of years of life, these markers, they're all over the page. And we can't actually rely on them to be reflective of an adult population.

Lisa: Why are they all over the place? Is it just because we're developing our systems and our immune system?

Brad: Infants are developing. So, generally, what you'll see is much higher levels of calprotectin, zonulin, and secretory IgA in infants. That's not to say it's a bad thing, it's just, well, there isn't enough research to validate the reference ranges in that population group. And the other thing to consider is, well, they're developing, and so it does change.

Lisa: And so can you just outline... I've just had a thought that sometimes there are students listening. What exactly is secretory IgA? What does it do?

Brad: So, secretory IgA, it can be considered a marker for intestinal inflammation because it's strongly correlated with faecal calprotectin, a very validated marker for intestinal inflammation. Now, if someone has high faecal secretory IgA, generally, the patients would present with IBS type D, lupus, intestinal permeability. But if someone had low levels — now, this is where it gets really interesting — if they have low levels, the research actually indicates that the patient might have some form of glucose metabolism disorder, which is very surprising and very unusual. I put this down because there's some early research that suggests that secretory IgA could actually play a protective role when it comes around to intestinal inflammation by limiting the inflammatory response. So, quite interesting.

Now, I have a theory, and this is based on my clinical experience utilising secretory IgA in clinical practice. So, there isn't any published evidence to back up this statement. But I like to think of secretory IgA like cortisol. So, as clinicians, we're well-versed in cortisol. I'll give an example here. So, if someone's very stressed, then their cortisol levels will generally be quite high. But if someone has prolonged stress to that point of...now, don't shoot me for using this term, but adrenal fatigue or adrenal insufficiency, then what will happen is their cortisol will bottom out. Now, what the research is actually showing is that its high levels of secretory IgA, which is associated with intestinal permeability, and inflammation, and autoimmune disease. But in my practice, I'm seeing patients presenting with low levels of secretory IgA.

So, my theory is initially patients will have an increase in their secretory IgA. But when there's prolonged inflammation and there’s prolonged immune dysregulation and disease, what will eventually happen is their secretory IgA will either the body will run out of the ability to produce it, and it will just bottom out, and that's when you'll get low levels of secretory IgA. So, that's just my theory when it comes around to secretory IgA, but I'm seeing it in clinical practice.

Lisa: I used to test the salivary cortisol all the time in a different clinic that I worked at, and we'd also test secretory IgA, but I think that was salivary. So, I'm not really sure then, if this kind of matches up with intestinal. But definitely, I can say that the people that had that ongoing chronic stress definitely had low secretory IgA, that lower end, and they were more prone to gut infections and parasites and things like that. I know there is some research in mice showing that prolonged stress, they do horrible things, they tie them up, and so on, and it does lead to changes in their secretory IgA, depending on whether it's prolonged stress or short bursts. But again, I think that's salivary rather than gut.

Brad: And that's exactly right. That could be very applicable to salivary secretory IgA. But when we're actually measuring stool secretory IgA and intestinal inflammation, we don't have any research to confirm whether or not the two are correlated. 

So, really, those four markers, the calprotectin, the lactoferrin, the occult blood, the secretory IgA, they are my functional markers I like to use in clinical practice. But as a lot of the listeners will be almost putting their hands up and almost be yelling at me, there is still a missing piece to the puzzle, and that is, of course, the microbiome.

So, the microbiome can provide so much information as to the driving factors for why our patients might be presenting with intestinal inflammation. Actually, looking at the microbiome, we can better understand whether or not our patients are at risk for intestinal inflammation and also determine how well they'll respond to treatment based on their microbiome. So, it's fascinating when you dive into the microbiome.

And when we measure the whole microbiome, a complete microbiome with meta-genomics, we actually have the capacity to look at over 28,000 species of bacteria in the gut, which is absolutely incredible. Now, from these 28,000 species, we generally see around 6,000 found in people's guts, not in one individual's gut, but across, let's say, a large community of people, there's generally about 6,000 more species. Looking at more of an individual level, you are looking at around 150 to 200 species of bacteria found in individuals' guts. Now, these bacteria, they can actually produce beneficial compounds such as butyrates or other short-chain fatty acids, but they can also produce bad metabolites such as LPS.

Lisa: Yes.

Brad: So, one of my favourite markers for intestinal inflammation in regards to the microbiome is something called Hexa-LPS. Now, Hexa-LPS stands for Hexa-acetylated lipopolysaccharides. Now, a bit of a mouthful, hence, why we can refer to it as Hexa-LPS. And basically, it's a pro-inflammatory compound that's found on species of bacteria within the Gammaproteobacteria phylum. So, there's a particular phylum of bacteria where these Hexa-LPS bacteria are generally found. What we know from early research is that Hexa-LPS can promote intestinal inflammation through activating particular immune receptors.

Lisa: Interesting.

Brad: Yes. Most clinicians would be well aware of LPS.

Lisa: Yes, because they are indicated with endometriosis, right, as an example?

Brad: That's correct. That's correct. But there's actually different subgroups of LPS. Now, what the research — now this is early, early research — but what the research appears is the subgroup of Hexa-LPS is the most pro-inflammatory, and then, thereby, something that we as clinicians will actually want to consider. I'll give you an example. I had a patient, couple of years ago now, he presented with Crohn's disease and had a long history of antibiotic use. I measured his microbiome and I actually found that he only had 22 species of bacteria in his gut.

Now, remember, as I mentioned just before, you usually find between that 150 to 200, okay? So, he only had a very few species in the gut. But if you actually look at these species and what they actually do in the gut, a good 80% of them are producers of Hexa-LPS. Meaning this patient's gut is just going to be so inflamed and the microbiome is just going to be contributing and contributing to the patient's inflammatory status because they're going to be producing this pro-inflammatory compound.

Lisa: Okay. So you are saying that there's a test, the HEXA test?

Brad: Yes, you can do a stool test to measure Hexa-LPS in the stool, and looking at particular bacteria. So, an example of that is E. coli. So, E. coli is a Hexa-LPS-producing species. So, you can actually look at the bacteria in the gut and understand their function. I'm not sure about you, but when I was at college, and even when I was teaching at college, my understanding of the microbiome was you have Lactobacillus and Bifidobacterium. And I'm sure there's clinicians listening going, "Yes, that's my understanding." But as I said, there's 6,000 species of bacteria in the gut.

There's so much more than just Bifidobacterium and Lactobacillus. Yes, they are beneficial genus probiotics, but when you actually look into the gut, there's different species of bacteria. And the way I like to look at it is rather than trying to understand how each and every species of bacteria functions in the gut, I like to look at them and go, "Well, what is this bacteria actually producing? What is its function in the gut?" If you understand its function, you understand whether or not it's good, bad, or somewhere in the middle.

Lisa: Yes. I just find it incredible when I think about the bacteria and what they do. I didn't learn it at uni either, but it was only five, six years ago that I learnt that our bacteria actually produce GABA, serotonin, dopamine, and so on. It's just incredible to think that they're so complex in what they do.

Brad: Yes. And they can produce that, but then they can also consume it. So, you've got bacteria that can actually consume GABA, that can consume dopamine. So, it's looking at it from a very comprehensive level and looking at all the species in the gut.

Lisa: And what about fungi as well? Because we focus a lot on bacteria, but there's viruses, there's fungi within us too. Do any of these tests focus on those?

Brad: You can look at fungi. But the thing that, and I was writing a blog probably about a year ago now, and I probably spent a good month or so just diving in and understanding fungi in the gut. There's a lot of confusion in the literature in relation to how much fungi should we have in the gut, what level of different fungi should we be having in the gut? 

My conclusion when it comes around to fungi in the gut is it's about the environment. We really need to have a good environment in the gut, taking out excessive sugars to have a gut that's not going to be irritated and then result in inflammation. And then it's also about ensuring that there's bacteria that are going to be beneficial. So, if we can actually increase beneficial bacteria, then it generally balances out these fungi in the gut.

Lisa: Okay. Interesting.

Brad: Yes. So, other, let's say, beneficial bacteria, are ones that can actually produce your short-chain fatty acids, right? So, your short-chain fatty acids include your butyrate, your acetate, your propionate, and low levels of these bacteria that produce these short-chain fatty acids has actually been linked with intestinal inflammation, right? So, butyrate can reduce intestinal inflammation through promoting the development of anti-inflammatory Treg cells by inhibiting the activation of NF kappa beta, inflammatory pathways, and actually modulating these pro and anti-inflammatory molecules.

Lisa: So, is that one of the biggest causes of intestinal inflammation that you typically come across in clinic, dysbiosis?

Brad: It's a driving factor. I can't say it's the complete factor because, at the end of the day, you could have the wrong diet, you could have H. pylori, you could have stress, you could have the diagnosis of a disease based on epigenetics and genetic factors. But the microbiome is a driving factor for disease, and it can also be something that protects us from intestinal inflammation. So, if you've actually got low levels of these short-chain fatty acids, that will actually increase that risk of intestinal inflammation. So, I don't think we can put down that it's solely the cause, but it's definitely a factor that we need to evaluate in every patient that has intestinal inflammation to understand, "Well, do we need to treat the microbiome? And then what aspect of the microbiome do we actually need to treat?"

Lisa: I do like that a lot, what aspect do we need to treat? Because... I know I'm coming back to the fungi, again, but I was really interested in reading a paper on children with type I diabetes. And they actually found that fungal dysbiosis, not just bacterial, was an initiator of intestinal inflammation in those children, which then led to that autoimmune disease activating. I feel like fungal dysbiosis is a big driver as well for individuals, not just bacterial, but I guess that comes down to immunity and stress because those are the things that can often increase that fungal overgrowth diet, as you mentioned, also a contributor.

Brad: And it comes down to inflammation. We understand as a core principle of modern disease and autoimmune disease that inflammation is a driving factor. I mean, how many times do you sit down with a patient, and you almost in your mind map, you write down ‘inflammation’ and you circle it, you go, "Okay, this is something I want to be addressing with my patient?" And actually understanding and measuring intestinal inflammation correctly and getting the whole picture can actually provide us with so much more inflammation than just going, "Okay, yes, the patient has gastrointestinal symptoms. I think it's intestinal inflammation, I'm going to prescribe curcumin."

Lisa: Yes.

Brad: Now, yes, of course, curcumin's going to help bring down intestinal inflammation, but it's going to help to bring down inflammation as a result of elevations in calprotectin, but would it necessarily bring down inflammation where there is the wrong bacteria in the gut or no bacteria in the gut that produce short-chain fatty acids? Probably not.

Lisa: So, when should clinicians then test their patients for intestinal inflammation?

Brad: That's a great question. And it almost comes down to three major components. They were your clinical symptoms, the patient's health condition, and then, in particular, let's say clinical situations. So, we mentioned at the beginning of the podcast clinical symptoms, so I won't dive into that in too much details. But if the patient presents with gastrointestinal-related symptoms, you would be thinking, "Oh, what's the cause here? Could there be intestinal inflammation?" That's one component. 

The other component that would almost ignite a clinician's thought pattern onto when they should measure a patient for intestinal inflammation is in particular health conditions. Of course, what we mentioned before, your inflammatory bowel disease, lupus, your ankylosing spondylitis, and then I think, most importantly, in undiagnosed IBS, to really determine, is this IBS or is this something more serious? Okay? So, there's particular clinical situations.

So, I'll give the example. A patient will present with loose stools, bloating, and cramping. Sounds like every second patient that walks in my front door. These symptoms, yes, of course, indicate IBS, but they could actually also indicate IBD. Now, the only way we're actually going to know is if we actually evaluate intestinal inflammation. If there's no intestinal inflammation, then it's going to be more likely to be IBS. But if there is intestinal inflammation, it's more likely to be inflammatory bowel disease.

Lisa: Yes, I agree. I think doing that more extensive testing is really important because often patients are just told they've got IBS and put on a low FODMAP diet, but maybe we are missing a lot when we don’t test.

Brad: Exactly. And that's the last thing you want, is to actually miss something more serious. In my practice, I like to go, "Okay, let's start with the most serious, colorectal cancer, work my way down, and rule out the most serious conditions." And if it is dysbiosis, then, fantastic. I can treat that, no problems at all. 

Other clinical situations you might think about measuring a patient for intestinal inflammation is actually monitoring disease. So, if you have a patient that already comes with a diagnosis of inflammatory bowel disease, I actually like to measure my patient's status of intestinal inflammation every 6 to 12 months. Because it's monitoring. It's to use, "Oh, are you at risk of a relapse? Are you heading down a disbiosis state? Can we get a better understanding of what is your normal when it comes around to these markers?" And really, the last one I like to do is almost, depending on the patient and depending how severe their intestinal inflammation is, is to actually do a retest to see whether or not the treatment I've actually prescribed has worked.

Lisa: Yes. I really agree on that one because I lose count of the number of clients that just say, "Oh, I've felt better and I didn't retest to check if my parasite or whatever was still there." I think it's really, really important that we are testing frequently to see, to get an understanding of what we're doing well, and if it's gone and the inflammation is down, and so on. Yes.

Brad: And the other thing I love about retesting is — I’m putting on my research hat here — is case studies. We have some great conferences here in Australia and globally that clinicians can actually present case studies where they have a patient, they come in with these conditions, they test, and then they treat, and then they retest. And they can actually present this at a conference and advance our understanding and actually talk about their treatment protocol, why they did it, and what improved and what didn't improve, and actually help educate other clinicians in our profession.

Lisa: So, talking about treatment, what are your favourite, what are your best kind of treatments for managing an intestinal inflammation?

Brad: I don't think I could blankly say “This is my protocol,” because it's such a personalised approach. It comes down to what are their clinical symptoms, what health condition have they been diagnosed with, which markers of intestinal inflammation are elevated? One of the biggest mistakes I see newly graduated healthcare practitioners doing is just going, "Oh, there's intestinal inflammation based on inaccurate or one test, or one marker inflammation, let's do a treatment. Away you go.” Exactly what we've just been saying. But I give the example, well, what if the patient had undiagnosed inflammatory bowel disease? You wouldn't actually know unless you actually did a very comprehensive assessment.

So, when you have a comprehensive assessment, you can evaluate, first and foremost, before you do any treatment, do you need to refer? Okay? I just want to highlight when you should refer before I dive into treatment. I like to refer on three different occasions. When there's high lactoferrin. If someone presents with high lactoferrin and they haven't been diagnosed with an inflammatory bowel disease, I'm writing a referral letter and I'm sending them off to their GP for further investigation straight away.

Lisa: Sure.

Brad: Calprotectin. Now, if calprotectin is suboptimal, I probably wouldn't refer. If calprotectin is between 50 and 100, I would take it based on their clinical symptoms. If calprotectin was over 200, I would say this has a very high degree of being accurate to identify something's going on, I need to refer, right? The last one I do for referrals is anytime that there's an unknown reason why there's occult blood in the stool.

Lisa: Of course. Yes.

Brad: So, once you've ruled those out, then you can dive into, all right, let's get down to the treatment. Some of the main treatments I like to consider, and these have been shown to bring down calprotectin, is things like...now, this is going to be ground-breaking: curcumin!

Lisa: I knew you were going to say that.

Brad: Got to start with my favourite. Curcumin, it actually has a substantial level of evidence to show that it brings down intestinal inflammation.

Lisa: Okay. And what sort of dosing are we looking at there?

Brad: This is interesting because when it comes around to the dosage, do you want it to stay in the gastrointestinal tract or do you want it to be absorbed? I'm in two arms about it. Sometimes I like it to be absorbed relatively effectively. The key thing here about dosage is you want to ensure that you're taking it twice a day, just from that half-life component of curcumin.

Lisa: Okay.

Brad: Other, let's say, known, we'll start off with a few more known interventions. You've got your omega-3. We can't forget about omega-3. Good quality fish oil can go a long way at bringing down intestinal inflammation. Your aloe vera can bring down intestinal inflammation.

Lisa: Do you find aloe vera, because it does have laxative properties too, how do you find that goes with intestinal inflammation if there's already looser stools?

Brad: You see, that's the interesting component. When a patient presents with intestinal inflammation and loose stools, why does the patient have loose stools? Because of the inflammation.

Lisa: Oh, very good.

Brad: If it's mild… so that the research here is, it's there, but it's still not high-level low risk of bias. If there is mild inflammation, I'd be thinking of aloe vera. If there's quite severe levels of inflammation, then possibly not. I'd be more going down the root of curcumin and even your SB as well. 

The other one to consider in relation to the microbiome. So, if someone has high levels of Hexa-LPS in their stool, so if their microbiome is driving their intestinal inflammation like that patient I described just before, there's a number of ways we can actually bring down LPS. So, your good old GOS. There's been research to show that three grams of GOS for five weeks can bring down Hexa-LPS producing bacteria.

Lisa: Okay. And what does GOS stands for?

Brad: Oh, God, I should know this. Oligosaccharide, fermentable carbohydrates. Okay.

Lisa: So, five grams has been shown to decrease Hexa-LPS?

Brad: LPS.

Lisa: Wow.

Brad: So that was three grams.

Lisa: Three grams.

Brad: The trick here is you want to start low and go slow. If you come in with five grams and someone's got elevation in Hexa-LPS, they're not going to be your friend, they're probably not going to come back.

Lisa: What's going to happen? What happens?

Brad: You'll have bloating, you’ll have change in bowel motions, you could have abdominal cramping. It's quite common to have mild gastrointestinal adverse events when doing high-dose prebiotics.

Lisa: Yes.

Brad: So, start low and go slow.

Lisa: Yes, I've definitely found that. 

Brad: The beauty of GOS is it actually reduces the bacteria that produce LPS. So, it's not just reducing the end product, it's actually reducing the bacteria known to produce LPs, which is absolutely incredible. 
The other very important component here when it comes around to LPS and intestinal and also systemic inflammation is the amount of fat in the diet. So, when we have high levels of, especially saturated fats, it can actually bind onto Hexa-LPS and bring it into circulation, going through the liver and resulting in systemic inflammation. So, a treatment recommendation I like to recommend my patients is to actually ensure that they're not having too much saturated fats and actually increase their omega-3. And who knows, actually increasing their omega-3 might bring down their intestinal inflammation.

Lisa: That's really interesting because I wanted to ask you actually about something like the carnivore diet and even the ketogenic diet. How do they impact the microbiome? Because a lot of people that follow the carnivore diet love it, they swear it's helped their gut complaints.

Brad: I don't know if it's just me or if other clinicians can relate. But I've had a number of patients where they basically just eat a beef, they just eat meat. They just eat bacon, eggs, and beef. And I'm looking at their food diary, I'm like, "No, this can't be right." But that's their food diary. At the end of the day, short-term, that's going to be beneficial in some individuals because we know that, let's say a cause of intestinal inflammation in clinical practice can be food sensitivities. Now, if you actually take out a large number of different food groups, different prebiotic fibres and allergenic foods like peanuts and eggs and so forth, and just eat a very ketogenic or carnivore diet, then your body's not going to be producing an immune response, and then, thereby, there will be less inflammation. And, yes, you will feel better. 

But at the end of the day, we've got this balance between arachidonic acid and omega-3. And if there's too much arachidonic acid, that's actually just going to result in a greater degree of inflammation later on. So, yes, short-term, the carnivore diet, you'll see some beneficial results. But long-term, it's actually going to be harder to get the patient back onto a balanced diet and actually address the root cause of the inflammation. I'm not promoting veganism, I'm not promoting the carnivore diet. I'm promoting balance. And if someone's reacting to food, we shouldn't be taking out that food group completely. We should be going, "Okay, why are you reacting to it?" And going about trying to amend the problem. So then the patient can have a very easy-to-follow balanced diet and it's not skewed to one macronutrient or the other.

Lisa: Yes, I agree. I definitely agree. And there's usually underlying dysbiosis that is the driver for those reactions. Okay.

Brad: Exactly.

Lisa: Now, big question. A lot of my clients ask me about colon cleansing, and enemas, and things like that, and they swear by them for their intestinal inflammation. But I'm really interested in your thoughts as an expert in this area because I have read some studies on colonoscopies — not that I would ever want someone not to have a colonoscopy — but that they can change faecal microbial diversity and composition. So, what are your thoughts here around colon cleansing, and enemas, and so on?

Brad: So, to touch on the colonoscopy, first and foremost, it's a risk-to-benefit ratio. The risk of not getting a diagnosis and the risk of reducing diversity in the gut verse the benefit of actually getting the right diagnosis to get the right treatment. So, I will say that someone who actually needs a colonoscopy, there's no question about it. Yes, it will change your microbiome. Yes, I've seen it in patients where we're doing so well, then they go for the colonoscopy, and then it takes three months just to get them back. I understand that, but it's such a vital and important component for screening. 

When it comes around to enemas, enemas and hydrotherapy, this is a really interesting component. So, as I mentioned earlier, our microbiome have got the ability to produce metabolites. Whether it's Hexa-LPS, or butyrate, or even beta-glucuronidase. Now, if, for some reason, there was a high level of these metabolites in our gut and we actually wash them out, yes, there would be a reduction in clinical symptoms. I give an example of, we've got a number of bacteria in our gut that can produce beta-glucuronidase, that can actually reactivate oestrogen and particular medication. And I've had patients who've got quite severe, whether or not it's endometriosis, or migraines, or hormonal problems. Now, their gut is actually contributing to that overall hormonal load. And actually doing an enema fortnight, actually kind of resets them and brings it back down to, okay, great, there's none of these metabolites floating around causing a problem. The problem here is you can become reliant on it. And I've had a patient before where they go, "Oh, yes, I do an enema every single day.

Lisa: Oh, my God.

Brad: "If I don't do an enema every day, then I have all these problems.” And it's like, "Oh, let's bring that back to maybe once a fortnight when needed and let's actually start supporting the gut." So, in some patients where they're quite serious and their microbiome are producing quite detrimental metabolites, I've used enemas in clinic practice. But as unsupervised form of treatment, I wouldn't recommend it.

Lisa: Excellent. All right. Well, my brain is bursting. There's so much good information that you have given us. Thank you so much for joining us, Brad. I could talk to you all day, I think, about the gut.

Brad: Lisa, it's been an absolute pleasure. You're a delight to talk to. And I look forward to listening to your podcasts here on FX Medicine.

Lisa: Oh, thank you, Brad. So, I think the three, I think about the main things I've taken away from today are that there are a range of different testings that we can use as practitioners to assist us with understanding and identifying intestinal inflammation that can often do, some of them are quite cost-effective through the GP, or we can order them ourselves. 
And then that fantastic three grams of GOS for reducing the bacteria that produce the Hexa-LPS. Hopefully, I've got that right. And the bloating. And then aloe vera, who would've known, great four reducing loose stools that are caused by intestinal inflammation.

Brad: That's right. They are three fantastic points to take away from this podcast.

Lisa: Thank you, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the FX Medicine website. I'm Lisa Costa Bir, and thanks for joining us. We'll see you next time.

About Dr. Brad Leech

Dr. Brad Leech is an internationally recognised Integrative Medicine Practitioner. After entering the functional medicine profession in 2008, Brad has taught and developed subjects at leading academic institutions in Integrative Gastroenterology, Naturopathic Medicine, Nutritional and Dietetic Medicine and Public Health Research. Brad is the Lead Clinical Educator and cocreator of Co-Biome. His expertise in integrative gastrointestinal healthcare enables him to translate the latest science on the gut microbiome into practical clinical applications. In addition to his research, and working with patients, Brad offers practitioner support through his mentoring program Brad’s Brainiacs. 

Connect with Brad

Website: www.drbradleech.com
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