Today I am joined by PhD-qualified clinical nutritionist Dr. Brad Leech. We talk about everything from the factors that reduce microbiome diversity to a user-friendly approach to the microbiome. Join us in this insightful conversation as Dr. Leech shares about the impact of HEXA-LPS, the importance of eating a diverse diet, if “leaky gut” is real, and a new way to look at “good and bad” gut bacteria. This conversation is packed full of information that everyone can benefit from.

Who is Dr. Brad Leech?

Dr. Brad Leech is a PhD-qualified clinical nutritionist with a background in Ayurvedic herbal medicine and nutrition. He has worked with supplement and pathology companies and currently works in a clinical practice seeing patients in the area of gut health and microbiome. He focuses on how we can improve gut health through the microbiome and improving the environment within the gut.

He has also developed different courses alongside universities and he is currently the lead clinical educator at “Microba” where his role involves educating practitioners and consumers on how we can understand and improve the microbiome from a very evidence-based but practical perspective. For example: instead of suggesting that someone should eat 60 grams a fibre a day, we can aim for 30 so the individual can tolerate it without bloating or sacrificing other macronutrients in their diet.

What Fostered Your Passion For The Microbiome?

In traditional Ayurvedic medicine, they have a large emphasis on your digestive system because they believe that disease begins in the gut. My initial education was very much focused on supporting digestive health. I started to venture into autoimmune conditions and as I ventured into my honors and PhD, I wanted to find the cure. My supervisors reminded me that I could not find the cure for all autoimmune conditions in a PhD so they had me focus on a tiny element when it came to autoimmune disease.

At this point, I stumbled across a paper by Dr. Pisano (who discovered the protein Zonulin), and he found that it contributed to increased intestinal permeability. He theorized that we could stop an autoimmune disease development by modulating the release of Zonulin and stopping this intestinal permeability. This led me down the track of gut health and intestinal permeability. I did a whole Ph.D. on that and I concluded that it is not just about barrier integrity, it is about everything that goes on within the gut.

This is when I realized that as clinicians, we have a basic understanding of what a healthy gut may be but as you dive into the research, you realize it is a lot more complicated and that there is a lot to improving the microbiome.

What is The Microbiome?

We have a microbiome on our skin, in our lungs, vaginally, and in our gut. The gut microbiome includes our mouths, stomach, small intestine, and the large intestine. The large intestine is where the vast majority of the microbiome is because this is where fermentation occurs. We can currently measure and sequence over 28,000 different species of bacteria. 10-15 years ago we were only looking at a few celebrities of the gut in the genus species and now that we have a broader understanding, we know that there are so many more.

From an individual perspective, we can generally see around 174 different species within the gut. We could sequence from 4000-6000 different species but if you had that many species you’d either be superman or very ill. To put this into a more realistic perspective, I work with ill patients with inflammatory bowel disease, who have only 20 species in their gut (and they are mostly detrimental). Then when you look at my gut, someone who has been a vegetarian, never taken antibiotics, never taken NSAIDs, was born vaginally, grew up on a farm, and all these key things that we're we're looking for, I have around 250 species.

If we take a step back outside of the Western world and look at other microbiomes, we can see that other cultures have a lot more species. I came across a paper that stated that tribes in Africa, on average, had 750 species in their microbiome.

The Factors That Are Driving Down The Reduction of Gut Diversity

There are a few things that really drive down the diversity of the gut:

Alcohol: I believe that in 10-15 years we will view alcohol the same way as we view smoking as a contributing factor to chronic disease. It increases our risk of cancer and impacts our microbiome. When we have large quantities of alcohol, it reduces the diversity in our microbiome and impacts our gut integrity and the environment within our gut.
Antibiotics, NSAIDs, and even antimicrobial herbs can impact microbiome diversity.
A low-fibre diet: When we don't have sufficient fiber in our diet, our microbiomes are starving. They need fibre for the fermentation of microbial metabolites and to produce beneficial compounds. When there's insufficient fiber, they start to die off or start to utilize mucin with that mucus layer within the gut.
Herbal urbanization: We are taking a step away from being in rural communities where there are cattle and other wild animals. I spent 5 years in Sydney in a small apartment and I know that my microbiome suffered because of that. Not getting out in nature can impact you. When my patients have low diversity, I tell them to get out in nature, garden, and get their hands dirty. This can also lower stress. Stress triggers our fight or flight response which impacts the release of digestive enzymes and that is going to reduce the ecosystem in our microbiome.
Chemicals in our food: Glyphosate is a highly prevalent herbicide that is sprayed onto crops and in local gardens. Small levels of these chemicals are damaging the microbiome diversity and impact certain species.
Antibiotics in our food: Meat is commonly pumped full of antibiotics to increase the muscle mass and weight of the animal.
Artificial sweeteners and preservatives: These are highly damaging to the gut microbiome. Our great-grandparents would never been exposed to these chemicals in our food supply.
Chemicals in our cleaning products: We are swimming in chemicals from our cleaning products, shampoo, and personal health products.

The Importance of Eating a Diverse Range of Plant Foods

We know that each plant product has its unique makeup of different prebiotic and dietary fibres Different species in our microbiome will utilize different prebiotic fibres as a fuel source. If we meet our daily fibre intake but it is from the same food every day, that is going to reduce microbial diversity. We have inulin, beta-glucans, GOS, FOS, and a variety more in all different types of plant foods. We should be consuming 30 different fruits, vegetables, nuts, seeds, and grains every single week.

Polyphenols are also important. We can get these from different coffee, tea, juice, herbs, and spices. So if you consider these as part of your weekly 30, it is not as difficult to meet. -Kriben Govender

Make sure that you are eating the rainbow. Eat every single color and every single part of the plant. Each part of the plant has different polyphenols, and prebiotic fibres which will support microbial diversity and the number of species found within your microbiome.

How to Work With a Patient with Digestive Issues

I’ve dived deep into the research and have also learned by trial and error. I have been seeing patients since 2008 and have been reminded to go slow with treatments. For example: if someone can't tolerate oats or a particular type of legume, we need to get a better understanding of why. Is it a SIBO-type picture? And if it is, can we support it with our own microbiome and gut capability to produce antimicrobial compounds to balance out the gut?

Then the trick is to start at a very low dose. Once I realize they can tolerate it, I tell them to add in a teaspoon of very well-cooked canned legumes. Wash them good and then the first week, start with a teaspoon every few days and then work your way up to one teaspoon a day. Then the second week, do 2 teaspoons every single day. If you had an intolerance to legumes before doing this and you added a bunch in at a time, you would end up bloating with diarrhea or constipation. This is why it is important to go low and slow.

Treating The Microbiome and Gut Integrity

When treating the microbiome and gut integrity, I use a synergistic approach where I treat multiple avenues at the same time. We know that gut integrity is influenced by the microbiome and vice versa, so if we just treat one element or ailment it is not going to have the best outcome. We remove the triggers from the diet, slowly incorporate dietary fibres, and then we can use targeted therapies to support leaky gut or increased intestinal permeability (if there's evidence for it.)

15-20 years ago there was an uproar about everyone having leaky gut syndrome. But I want to clarify, there is no such thing. A syndrome alludes to the fact that there's a group of clinical symptoms that can diagnose the syndrome, when in fact, my research has shown that there isn't a group of clinical symptoms to say that there is leaky gut syndrome. Leaky gut (increased intestinal permeability) is a reaction that happens within the small intestines. So it's really important to address that at the same time as the microbiome because they can impact one another.

HEXA-LPS

LPS (lipo polysaccharides) are a component of some bacteria. Some bacteria will have this on the outer layer of their cell membrane. We can look at something referred to as HEXA-LPS, which is a subgroup of LPS that is more inflammatory and linked with chronic disease. This is why we focus on HEXA-LPS.

We can have an increase in HEXA-LPS being absorbed within the gut, which can contribute to systemic inflammation. However, within the gut, HEXA-LPS can induce intestinal inflammation and permeability through the TR4 receptors. HEXA-LPS within itself is linked with intestinal permeability but also with different types of gut inflammation.

From a clinical perspective, we want to reduce this microbial metabolite and production from the microbiome. It is linked to health conditions like inflammatory bowel disease and people who have that condition have a higher abundance of HEXA-LPS-producing species in their microbiome. If we can reduce this, it can translate into an improvement in clinical symptoms.

Gut inflammation, systemic inflammation, and clinical symptoms, such as pain, bloating, and cramping at all signs of gut inflammation. When there's gut inflammation, the microbiome is not happy and good species cannot thrive in an inflamed gut.

What Species is The Key Driver of HEXA-LPS?

There are a lot of different species that can produce HEXA-LPS such as: E. coli and Klebsiella, there are a least 40-60 species that can produce it. It is not just understanding specific species but also collectively, how much HEXA-LPS is your microbiome producing? Because the species on their own may not produce that much but when there are a lot of them together, that is where there is an abundance of HEXA-LPS.

Is HEXA-LPS a Concern in a Healthy Gut?

This depends on how high it is. If it is elevated above what we see in a healthy cohort, then it can cause gut inflammation, systemic inflammation, increased intestinal permeability, and been linked with several different chronic health conditions. There are so many different microbial metabolites, you can view such as: branched-chain amino acids, IPA, and TMA, which are all part of our microbiome. But HEXA-LPS is one of the main markers that I look for.

HEXA-LPS

How to Tackle HEXA-LPS

In the past, we would have thought “Okay, there is E. coli, we are going to give an antimicrobial herb, a high dose of berberine, oregano oil, or any other herb to kill it.” Within the last two years, research has come out which shows the impact of taking antimicrobial herbs on the whole microbiome. I came across 2 research papers that showed those who took Berberine supplementation of 1000 milligrams for three months, had a reduction in butyrate-producing bacteria and an increase in HEXA-LPS-producing species.

Taking anti-microbials is not going to be the most appropriate course of action when it comes to HEXA-LPS. So I thought about this and asked myself “What other interventions can we use?” We can have a more balanced fat ratio and consume less saturated fats, consume more omegas threes, which is going to reduce the absorption of HEXA-LPS from the gut into systemic circulation. But there's still going to be HEXA-LPS within the gut.

Then I came across a study that used Galacto-oligosaccharides (GOS) supplementation to reduce HEXA-LPS-producing species including e.coli. This study involved older individuals taking 4 grams of GOS for three months. They found that there was a reduction in HEXA-LPS-producing species. So rather than looking at LPS from a “we need to kill it” standpoint, I consider it a “we need to feed the microbiome” approach. When we nurture the gut web, we are supporting those species that are already there to nurture them to bring them up and then the detrimental bacteria can die off and you have a more diverse, healthy, and balanced microbiome.

When prescribing GOS for my patients, the vast majority of them have been sensitive. They have a variety of different health conditions going on so starting at a low dose is key. I normally start at one gram a day and work my way up. I might do one gram for a week then increase that to one gram twice a day for the next week. Or I would do one gram for three days and increase it by one gram for three days. Adding a lot at first will cause bloating if you do not have a healthy microbiome.

The Benefits of Different Types of GOS

Beta GOS has proven effective in clinical settings based on studies. Some recommended prebiotics in the market include sunfiber partially hydrolyzed guar gum. The choice of prebiotic fibre should be based on an individual's microbiome.

Partially hydrolyzed guar gum is beneficial for supporting the production of certain traits and alleviating clinical symptoms, especially for constipation. It is gentle on the gut and aids in bulking the stool and supporting peristalsis and motility. The suggested dosage for constipated patients is around 10 grams at night. I incorporate small amounts into daily smoothies for diversity, along with GOS and HMOs to feed a variety of different species. It's important to start slowly with pHGG, as it is FODMAP-friendly and suitable for those with sensitivities!

The Technology Around Microbiome Testing

There are so many different ways we can measure the microbiome: through culture, 16s, qPCR, and metagenomics. In Australia, the vast majority of ways we can measure the microbiome is culture qPCR and metagenomic and in the UK and US, 16S is more readily used.

Culture: The reason why I'm not utilizing culturing in clinical practice is because it's only able to measure about 5% of the microbiome. This is because it's exposed to oxygen and we know that there is no oxygen in our large intestine. So if we take a stool sample out and expose it to oxygen, then we end up growing things like Candida and it gives us false information.

qPCR: If you want to look for Akkermansia muciniphila or streptococcus genus. It's very accurate in giving you how much is there but it is not telling you what else could be there. There are only around 100 different “probes” to use in qPCR technology but in most microbiome reports you generally see 20-30 different species. For example, if we compare qPCR to metagenomics it's like using a flashlight in a room versus turning the switch on and seeing everything.

Metagenomics: This looks at the DNA of the bacteria and then we can identify it but also see what it uses as a fuel source, what metabolites it produces, and their function. With metagenomics, we can see all of the different HEXA-LPS-producing species and combine them based on the genetic profile to say, “This person's microbiome can produce a lot of HEXA-LPS.” There's a variety of other microbial metabolites that we can look at using metagenomic sequencing including: HEXA-LPS, branched-chain amino acids, IPA, TMA, methane, and hydrogen sulfide. We can look at the function of the microbiome instead of just who is there.

A User-Friendly Way to Look at the Microbiome

If you were to get a list of the 184 species that are in your gut you would end up thinking “What am I supposed to do with this information?” But if I provide you with the function of your microbiome, then you can take a step back and ask yourself “How do I reduce or increase xyz?” This is more of a user-friendly approach so you do not get overwhelmed. I have been studying the microbiome for 15 years and I still do not know every species. It is not humanly possible to know the function and treatment of every single one.

In every report I look at, some species have never been documented in the scientific literature. But we can look at the DNA and function of it and say “Okay it is producing short-chained fatty acids so it could be beneficial.” This is such a more clinically useful way of looking at the microbiome.

When I look at patient's stool profiles and certain disease elements are present, it is useful to have an understanding of where the deficiencies are. It is great to start with wins and then talk about the deficiencies and make dietary or supplement recommendations. This also highlights things like the microbiome creating B vitamins so you can save some money if you are worried about your levels. -Kriben Govender

We know that the microbiome can produce a number of different B vitamins, including folate, but the research out there on whether or not they're absorbed systemically, and whether we can utilize it not, is still not understood.

The Impact of Antimicrobials on The Microbiome and Functional Dysbiosis

I am passionate about two different areas at the moment: The impact of antimicrobials on the microbiome and functional dysbiosis

For many years, clinicians have been saying “You have disbiosis” to their patients. I want to change how we refer to dysbiosis and say that you have functional dysbiosis. And that comes down to the function of the microbiome. So if I were to say “You have a functional dysbiosis with a low potential to produce butyrate”, that provides you as a clinician with a lot more information rather than just saying “dysbiosis” with no other explanation.

And then the other area I'm quite interested in at the moment is pathogens and pathobionts and how we can go about treating the balance of them within our microbiome. For many years, we had this understanding of pathogens in our gut where we would look at a particular species or genus and say, “I have a pathogen, I have to kill it.” But a true pathogen is a pathogenic strain, NOT a species.

Pathogenic strains need medical referral. When someone has a pathogenic strain such as E. coli strain 01597, where it's causing acute diarrhea. I'm not going to be playing around with prebiotic fibres to support the microbiome. I'm going to write a referral and send it to the GP to get antibiotics to kill that pathogenic strain.

But there's this concept of pathobionts. A pathobiont is a microbial species associated with a negative health outcome. In metagenomic research, we are seeing certain species statically higher in those with chronic disease. They are not a pathogen and we are not trying to kill them but we can see through cross-sectional data that it is a pathobiont. We cannot treat a pathobiont the same as a pathogen, you just need to support and nourish the microbiome. If somebody came to me and in their microbiome report had a variety of different pathobionts, I'm going to be looking at the abundance of them and see if they are causing a problem. Then I would understand the different causes of the problem and treat the cause.

For example: The genus Streptococcus can have oral base species. Now when there's a higher abundance of oral base species, these are pathobionts. They are species found in your oral cavities, nose, throat, and mouth, and then they are identified in your stool. But how can species of bacteria in your mouth survive this whole transit down to your anus? This would be because there is a lack of stomach acid. As a clinician, I use that in my tool belt to say “Rather than trying to kill this potential streptococcus saliva species, I'm going to support them with their stomach acid production.” I might do so with bitter herbs, apple cider vinegar, digestive enzymes, hydrochloric acid, or zinc, to support stomach acid production. Then oral species won’t be found in the intestinal microbiome.

The other factor when it comes to pathobionts management is feeding up the other beneficial bacteria. So incorporating beta-glucans (found in oats) and fermented foods (such as fermented vegetables, milk kefir, or kombucha) into your diet, are key strategies to feed the microbiome so that these pathobionts won’t take up as much space in our gut.

I love this new approach because the old way was that you nuke the gut and start again from scratch. When you look at it like in any ecosystem, if we went to a wild rainforest, nuked the whole thing, and tried to start again from scratch, it's highly unlikely that it's going to grow back into a vibrant rainforest. There's so much complexity and things we do not understand. - Kriben Govender

Blastocystis and Dientamoeba Fragilis Parasites

Before we had this more advanced understanding of the gut microbiome, we wanted to treat blastocystis with antimicrobials so we could treat and kill it. I believe this did more harm than good. Now with the change in understanding the microbiome, we can actually view blastocystis and D fragilis as part of the ecosystem. An issue only occurs when the environment in the gut is compromised and under an impact. Just because they are there does not mean that there is an issue. I have D fragilis and no gut issues at all.

I know some patients who are still concerned over their blastocystis but we need to take step back and see what else is happening in the gut: are they stressed? Are they having regular bowel movements? Let’s not try and pinpoint blastocystis as the cause because from my experience, trying to kill it is very difficult, going to compromise the microbiome, and when you do kill it, there's not a change in clinical symptoms.

I now look at microbes as genetics and a form of an organ with different genes that produce metabolites. At the end of the day, the actual benefits are exerted either from the metabolites that they're producing or they're the succession of different bacteria, yeast, fungi, and microbes, to an end metabolite. So that particular pathogen, parasite, or pathobionts might be being kept in check by other organisms or they might be part of a succession where one is feeding off the other. We often try and paint a good guy and a bad guy but I think that the good guys can be bad, and the bad guys can be good. - Kriben Govender

Why is Microba Stool Testing Useful in a Clinical Setting?

Functional testing needs to inform treatment direction. We need to be able to say “The results of this test are going to change how I treat my patient.” That's why I utilize microbiome testing in my clinical practice because I need to know what is happening in the gut. I do not want to just guess and give you something, I want to base it on the report and give you personalized medicine based on what your microbiome is doing.

Rob Knights 16S Translation to WGS

16S was the predecessor for whole genome sequencing, It was a cheap, very fast, and effective test looking at RNA as a marker. But now Rob has done some work where they can look at older studies and match them with whole genome sequencing. I previously thought that all of the 16S ones we going to be rubbish and outdated but now with this new data available, it helps to bring these studies together in a more unified way. Whole genome sequencing is the gold standard and any modern company should be utilizing that technology. I am excited to see how that space evolves. -Kriben Govender

It also depends on the database they utilize. Sometimes researchers can use 16S or metagenomics but their database is so small and is not going to provide you with enough information. You have to dive deep into the research to understand what database they are using and that will provide you with a more robust understanding if it is surface-level metagenomics or deep metagenomics.

Make sure to connect with Dr. Brad Leech through his website and share this with a friend who could benefit from this information!