How to Build a Resilient Microbiome

Have you ever wondered why people worry about gut health? Did you know that gut health is directly correlated with many chronic diseases? I had the pleasure of speaking with Kiran Krishnan. He is one of the founders of Microbiome Labs and they have created an amazing product that will help you rebuild your gut health. Read on to learn about why type two diabetes is affecting us at a younger age, how you can heal from leaky gut fast, why a spore-based probiotic is above your conventional probiotic, and why your gut health is key in avoiding chronic illness.

What is Your Background and How Did You Get Into Science?

I always say that I am a simple kid from the villages of India with a high degree of curiosity for the world around me. I was never one to take for granted how things worked. When I came to the states for the first time and there were so many things that people used that were commonplace that to me were completely foreign, like the microwave. A lot of my friends knew how to work one but they didn’t realize exactly what was happening. That was the curiosity that I had. I never wanted to not understand the world around me. 

Watching my mother work at her medical clinics is what steered me towards science but Hollywood is why I specialized in microbiology. In the first week of college at my dorm, I saw a movie called “Outbreak”. It was about a virus that came in on a monkey and caused a massive outbreak of a terrible disease. Underneath all of the action, there was a group of scientists that were running around trying to find an antidote. That is what triggered me to do what I am doing. The very next day I enrolled in the school of microbiology and that is how I started.

How Would You Describe Your Gut Health, and What Does Great Gut Health Look Like?

The way I would describe my gut health is with one word…. Resilient. I think that should be the goal for most people and their gut health. As a species, humans are omnivores. Some people are vegan, paleo, or carnivores but for the vast majority of human existence, we have been omnivores. We are lucky because we can eat many different things. We can eat all along the spectrum of biological abundance around the world including:

Nuts

Seeds

Roots

Insects

Animals

Plants

We can survive on all of these through many different conditions and that is VERY important. When you look at the course of human evolution there were many instances that we could move up the food chain because of:

1. Our intelligence
2. Our ability to eat a diverse diet.

For Example: If you think about a lion, they are carnivores. A lion cannot eat plants, it would get sick and die. A lion is extremely dependent on the population of wildebeest and mammals that are walking around in the savanna. If there is a drought and the herbivores food source gets hampered then the lion’s food source will as well. For humans, if there is a drought we can go eat termites, weird roots, and so many other things to survive. The reason for this is that we had gut resilience. Now we have so many people that are so sensitive to big groupings of foods. I know many people that can't eat eggs, dairy, wheat, grains, nightshades, and soy. They can't eat these because they would have a negative adverse effect on them. Also, their guts tend to be sensitive to even minor changes in their work or environment like:

-Stress

-Traveling

All of these things create an impact on their gut health which then impacts their overall health. My focus has been to build resilience in my gut. I want to be able to eat anything. Imagine going to a restaurant and having to quiz the waiter on the chances that your dish would touch gluten in the kitchen. This is the reality for many people. There are too many people that live with low resistance in their gut and are very sensitive to any changes outside of a narrow range.

Having resilience and being able to eat all food groups is the most ancestral way to exist. We should always make the right food choices…. Don't eat burgers and fries all of the time but you also shouldn't suffer for a week if you have croutons in a salad. You need to build resistance and live. If you have to be overly diligent on what you eat it dampers your quality of life. 

Just having a resilient gut would give many benefits to people around the world because gut health is such a huge area of dysfunction around the planet, especially in the western world.

Why Are Our Guts No Longer Resilient and What is The Best Way to Build a Resilient Gut?

An analogy I always give people is that we are a Holobiome. This is defined as a:

Superorganism: an organism that is made up of a grouping of thousands of other organisms. 

They work together to perpetuate the health of the entire ecology. We are a walking, talking, rainforest. We have all of these microecologies in different parts of the body that have to communicate and support one another. Metabolites that are produced in the gut: feed the bacteria in the vaginal canal, the eyes, and the blood. All of these areas that we thought were sterile we now know they are all colonised by:

-Fungi

-Bacteria

-Viruses

There is nothing sterile in the human body, we are a microbial construct. Then you take these colonies and put them in an antimicrobial world. Everything around us kills bacteria…..

-The chlorine and fluoride in our drinking water

-The round-up and pesticides on our food

-Antibiotics

-Personal care

-Preservatives in foods

All of these are designed to kill microbes…. and WE are made up of microbes. Because of that, we diminish our resilience. We bring down populations of really important, healthy bacteria that add to the resilience of our ecology. 

These are three tips to build a resilient microbiome:

1. Minimize your exposure to things that harm the microbial ecology in the body. If you can, choose organic food because it will have fewer pesticides. Try to filter your drinking water. If you don't have to take antibiotics, don’t, because more than likely the sinus infection that you have is a viral infection, not a bacterial infection. Be wary of your personal care products because they are full of crazy antimicrobials that have not been tested on humans. You can't eliminate your exposure but you can minimize it so it has less of an impact.
   
   
2. Maximize your exposure to microbes in the outside world. I try to get as much exposure as I can. I try to be outside as much as I can. If I go for a hike on a trail and I am going to be eating a sandwich I won't be using hand sanitizer. You want some of the dirt from your environment on your hands and in your system. Here’s an example called The Finnish Allergy Study: There are two towns, one in Finland and one in Russia. They are about 100km apart and the geography in the region is very similar. But in the Finnish town, they have high rates of allergies and asthma. In the Russian Town, they have far less allergies and asthma. What is causing the difference?  
   
   When they looked at 100’s of people, their homes, families, they found one difference between these two towns that could be impacting their health. In the Russian town they kept their doors and windows open more often, this means that the microbiome could come in and they didn't sterilize their home. They didn't clean their home with antibacterial cleaners that said “kills 99% of bacteria” on the bottle. This means that their home had a good abundance of bacteria that come in from the outside all the time. That exposure to bacteria all of the time curbs their development of allergies and asthma. 
   
   In the Finnish town, they kept their windows and doors closed far more often. Less fresh air and bacteria came in and they cleaned their surfaces all of the time because the culture in Finland is that everything should be sterile and smell like cleaners. They believe that this represents cleanliness but it represents illness. The lack of exposure to microbes causes that problem.
   
   
3. Eat a diverse diet! You don't have to follow any particular diet because our ancestors didn't follow these diets. They ate what they could gather, forage, and what they could hunt. Anthropological studies show that humans consumed as many as 600 different types of foods annually. If we look at a current western diet we consume around 20 different types of foods annually! That is an astronomical difference. Increasing the diversity in your diet will increase the resilience and diversity of your microbiome.

Minimizing exposure to antimicrobials, increasing your exposure to microbes, and eating a diverse diet will allow you to develop a more resilient system. Spend more time outside, increase the diversity of your diet, and bring in probiotics.

What is Metabolic Endotoxemia and Why Is It An Issue?

When I speak about it at functional medicine shows I often ask doctors “how many of you have brought a patient in, done a full history, blood work, and then written down the diagnosis of endotoxemia?” I always get a laugh because no one has ever done that. BUT if you look at the signs it is the major driver of 90% of chronic illness. It is so prevalent that the American Diabetes Institute and the American Heart Association are all studying metabolic endotoxemia because it is such a driver in chronic illness. It is a fancy term for leaky gut and the most prevalent type of leaky gut. Let's break it down:

Metabolic: The process of breaking down food, converting food to energy. The process of eating

Endotoxemia: Endotoxin is a toxin derived from within, not a toxin that we are exposed to from the outside like a mold toxin. And the emia part means that it is in the blood. The toxin is generated through the metabolic process and now ends up in the blood. That is how you would define it.

When your gut is leaky and you have metabolic endotoxemia, every time you eat you get a massive influx of a toxin called LPS (Lipopolysaccharide) This is a toxin that is found on the cell membrane structures of gram-negative bacteria….Every bacteria is either a gram-negative or gram-positive. One way of studying bacteria is to take them and stain them with red gram stains and look at them under a microscope:

-If they are gram-negative then the red won’t take= no additional cell wall structure

-If they are gram-positive then the stain will take and the bacteria look red= additional cell wall structure

What happens with gram negative bacteria (the ones that don't have a cell wall so the stain will not take) they have a compound in their cell membrane structure called LPS. It is a fatty acid with sugar on top and it's a transmembrane compound which means it sticks in the membrane of the bacteria. They use it for:

-Signaling to other bacteria

-Communicating with the immune system

-Binding with the mucus layer in the gut

When it is in the bacteria it doesn't cause any issues. BUT when the bacteria die, the cell breaks and it releases LPS to be free, it becomes a very potent toxin.. When our immune system sees this toxin floating around by itself it freaks out! This is because it indicates to the immune system that there is a bacterial invasion coming into the body. The immune system is not supposed to see high levels of this endotoxin in the blood. If they see it in the blood that means there is this bacteria in your blood, they are multiplying, and that is what is going to make you sick.

Many people have heard of “Sepsis” and how dangerous it is. You can go from being perfectly healthy, walking, and talking to being on death's doorstep in 24 hours. This is the same thing as metabolic endotoxemia, just a far more pronounced version of it. The blood infection is when LPS gets propagated and produced at too high of a level in the blood. What is happening is that there is LPS in the lining of the gut. There is a bunch of gram-negative bacteria in the ileum of the gut which is the tube that goes to your intestines. About 70% of the bacteria that live in your gut are gram-negative! 

During the digestion process, when you eat food, the bacteria will die. That is a normal process because of bile and digestive enzymes. When they die they will release the LPS. When this is released in the gut it is perfectly fine because:

-It is neutralized in the gut

-Bacteria will break it down

-You will poop it out a few hours later

-It won't cause any issues

BUT when your gut is leaky, the process of digestion releases LPS and the tight junctions, which is the space in between your intestinal cell lining are too porous. They open up and the LPS leaks through into your circulation. And it leaks through at a very high level. LPS Endotoxemia is defined as a 5-6 fold increase in the level of this endotoxemia in your blood within 5 hours of eating a meal. The problem with this is that it sets your body up with really potent long term CHRONIC inflammation. Because every time you eat food you are having a little bit of sepsis and it can:

-Concentrate in your knees as rheumatoid arthritis

-Concentrate in your brain where it causes Alzheimer's, Parkinsons, dementia, anxiety, and/or depression

It has many impacts all over your body and it happens when you eat. If your gut is leaky the only way to prevent it is to not eat and that is not a solution as a human! The most normal common thing as we all do as a human becomes the most toxic thing. It's more toxic than any other behavior because it sets you up for chronic disease…..

What is the Link Between Type 2 Diabetes and LPS?

In general, LPS in the gut that is allowed to translocate into the circulatory system because of a leaky gut lining is going to cause chronic inflammation which becomes the foundation for most chronic illnesses. The American Diabetes Association has published a dozen studies that show that LPS Endotoxemia is the primary thing that leads to diabetes. For example: There was a study that took 462 people that had a high risk in developing diabetes (they didn't have it yet!) They were obese, had a family history, and high cholesterol. They followed them for 60 months. They were measuring all of the different markers to figure out which markers had the best predictors of the development of diabetes. 

What they found is that there was only 1 marker including everything the doctor would test you for that accurately predicted 100% of the time that the individual was going to develop diabetes and that was the amount of LPS in their circulation. The more LPS in your circulation the higher the risk of diabetes. The paper suggested that using LPS levels in the blood as a primary predictor of the development of type 2 diabetes. Type 2 diabetes has been said to be the biggest pandemic that we are going to face as a health issue. 700 million people across the world are diabetic and they estimate that 4x that amount are prediabetic. At some point in the next couple of decades, we are going to have 5 billion people in the world that are diabetic. When you are diabetic it quadruples your risk for many other chronic illnesses like cancer, dementia, and Parkinsons. A dysfunctional gut becomes an underlying threat to humanity.

Is There a Mechanism That Leads to LPS Driving Diabetes in the Body?

There are a few mechanisms. Once LPS is in your system it can go through your blood, cross the blood-brain barrier and enter your brain. It will go into the hypothalamus and cause inflammation. This makes your brain dysfunctional in terms of reading your blood sugar levels. Your brain is supposed to tell your body what your blood sugar level is and release insulin in response to it. That causes something called central insulin resistance. Most people know insulin resistance as being an issue with your pancreas. That does happen but it is secondary! Part of the problem is that your brain can no longer communicate with the rest of your body. It cannot read your blood sugar levels correctly and then your pancreas starts producing insulin a lot of the time because of these crazy spikes in blood sugar levels. Your brain cannot control it. 

The LPS targets the islet cells in your pancreas. Those are the cells that produce insulin and the LPS starts killing off those cells through inflammation. It is a two-prong approach in causing diabetes. In the USA, we are seeing more cases of young people aged 18, coming into doctors offices that are not obese who don’t have metabolic syndrome but they have type two diabetes. Central insulin resistance (starts in the brain) does not have to do with your body weight. You can be lean but your gut is leaky and the LPS is getting in and causing the central insulin resistance.

Why is Diabetes Impacting Us At a Younger Age?

This is impacting us at a younger age for a few reasons:

1. We are finding out that the mode of birth will have a major impact. Over the last 25 years, we have pushed more people towards a cesarean section as an elective method of birth. There are a lot of people that have to do it for medical reasons but up to 33% of births are now cesarean sections. A good number of those are elective because it's easier and more convenient. Cesarean section babies tend to have higher dysfunctional gut microbiomes compared to vaginally birthed babies because they are not getting that important inoculate from their mothers’ vaginal canal. Right off the bat, cesarean section babies have an increased risk for:

-Immune dysfunctions

-Hormone dysfunctions

-Metabolic dysfunctions

 Because they aren't getting the full microbiome from the birthing process.

2. There is excessive use of antibiotics, especially with kids. The center of disease control in the USA gave an estimate that up to 50% of antibiotic prescriptions are unnecessary. They are being used for VIRAL infections. I talked to many doctors about this in places like urgent care centers where people come in for a cold or flu…. They are looking for a pill to make them better because they don't want to miss work. They are pressuring doctors to give them something. Even though the doctor knows they have a viral cold, they still give them antibiotics even though it won't help them. They know that if they don’t give them it then the patient won't come back to that urgent care center. 
   
   With children, the doctors feel pressured from the parents to give antibiotics when their child is sick. You can't blame the parents for wanting to relieve their pain but the parents do not like to hear the doctor say it is viral and it will run its course in a few days. Those unnecessary antibiotics can have a long term impact on the microbiota including leaky gut and building foundations for chronic illnesses. We are seeing kids from an earlier age having significant dysfunctions in their microbiome. When you look at things like Ulcerative Colitis, allergies, asthma, and Crohn's prevalence rates in young kids, they are all tied to gut dysfunction…..It comes down to metabolic endotoxemia.

What is a Probiotic?

“A live microorganisms when administered in adequate amounts confers a health benefit to the host.” There are a few things that are important in that definition:

1. It has to be a live microorganism that can get through the gastric system alive and enter into the digestive tract and function as a live bacteria.
2. There is a dose-response to it. If you dose it at this amount it will have this health outcome. 

It is a good bacteria that can give you a health benefit and it has to be alive.

How Are Probiotics Made and Where Are The Bacteria Derived From?

A lot of the conventional probiotics at your health food store or online are made up of lactobacillus and bifidobacteria and have 5-15 strains in the billion CFU dosage. The vast majority of those are derived from fermented dairy products, some of them are derived from healthy human volunteers, and all of them are produced by fermentation.

A few decades ago, when we were starting to understand that there are beneficial bacteria, a lot of labs in Universities were sampling different people. They were looking for microbes that lived naturally in different parts of the body. In some cases, they found certain microbes were having great effects within that person. Then they tried to take that same microbiome, grow it in fermentation, and then administer it in other people to see if it had a similar effect. 

The spores in our product, Megaspores, were isolated from healthy human volunteers a decade ago. We work with a University that looked for native bacillus spores that were natural colonizers of the human gut. They tried to isolate this bacteria from the volunteers fecal samples looking for human-derived functional bacteria. A lot of companies market their products as human-derived. This means that the bacteria was isolated from a human specimen at some point. If it is not human-derived then it is lacto-derived, from dairy.

What Is a Spore Based Probiotic?

They are a unique set of bacteria. You find them in the dirt, dust, vegetation, and streams. They are also in the human gut. They are colonized in the gut and also live in the outside world which is amazing! When you look at a bacteria that does that, it speaks to a unique feature and function of that bacteria. It would be equivalent to a human that could live on land and could also live 5000 feet below the ocean's surface...We know how different those two are. If you could live in both you would be a superhuman.

These are essentially super bacteria. They can live in the outside world where there is:

-UV Radiation

-Desiccation

-Oxygen-rich environment

They can also live inside the gut with:

-No Oxygen

-No Light

-Liquid and food moving through

-An Immune system

-Trillions of other bacteria

Another great thing about them is their ability to pass through the gastric system. This system is a gauntlet for bacteria because there are so many steps in the process of swallowing something that is designed to kill microbes….

1. Our stomach acid is very strong. If you have normal stomach acid you have a pH of 1.3. To understand what this means, if you had hydrochloric acid in a cup and it was at the pH of stomach acid and you stuck your finger in it it would burn off your skin. If you poured it on metal it would eat through it. That is called the gastric barrier because it kills the majority of the bacteria that are trying to get through your system. 
2. If the bacteria makes it past that there is something called bile salts. They are released in the small bowel and they are a strong antimicrobial that kills bacteria as well.
3. Then you have pancreatic enzymes that are there to break up food. They can kill bacteria as well. 

Bacteria have to survive through a lot to make it to the large intestine alive. We were looking for a bacteria that had a natural capability of surviving through this amazing gauntlet. That is where the spores come in…. They are called spores because when they are outside of the body or they are under stress they cover themselves in a thick protein classified armor. That armor allows them to survive through the stomach acid, bile salts, and the pancreatic enzymes and then get to the intestines completely alive where they can function as a live probiotic cell. We started testing conventional probiotics and we found that the vast majority that we tested were not surviving this gauntlet. We were looking for natural bacteria that had the ability to make it through and that is how we found and identified the spores.

Short-Chain Fatty Acids and Metformin?

There are prebiotics, probiotics, and postbiotics. Short-chain fatty acids are Postbiotics. Postbiotics are compounds or nutrients that are made by the microbiome and are essential to ourselves. The microbiome makes thousands of these because we need them to function as a human. We can't get these from anywhere else. Short-chain fatty acids are a great example of this, especially butyrate. 

Butyrate is one of the main short-chain fatty acids that has an impact on metabolism. You need adequate amounts of certain types of bacteria in your large bowel for them to turn carbohydrates into short-chain fatty acids like butyrate. Butyrate improves insulin sensitivity. If you have enough butyrate, your body can now detect insulin levels with more accuracy. It also stimulates all of these cells outside of your gut to use fat for fuel and burn off sugar. It is an important orchestrator of your metabolism. 

There is a compound called Metformin (which is the number one used prescription drug for people who are diabetic!) A couple of years ago it was discovered that the way metformin works is by increasing butyrate production in the gut. It is the butyrate that is produced by your microbiome that is resolving the insulin issue. 

The problem with the drug is that there are side effects and the effectiveness of it decreases over time so people have to increase their dose of the product. We did a study to see if we could naturally improve butyrate production with our spore-based probiotic and a prebiotic. We increased butyrate production by over 150% in 3 weeks! That has a huge impact on your metabolic health, inflammation, and is the best thing for leaky gut.

In a recent study, we also saw that it has an incredible impact on your skin. We just completed an acne study where we saw a significant reduction in acne lesions when you take the probiotics. One of the mechanisms is the increase in short chain fatty acids. We were able to see that people with acne had lower levels of certain short chain fatty acids and people with no acne had high levels of them. When we add in the spore probiotic the level of that short-chain fatty acid went up and that reduces acne!

For the prebiotics, we used a combination of Oligosaccharides. They are resistant to digestion in the upper part of the GI Tract and we don't get an insulin spike from having them. They go into the large bowel and they feed certain types of important bacteria especially the butyrate producing bacteria. The Oligosaccharides that we used were:

-FOS (Fructooligosaccharides) Derived from the pulps of Kiwi Fruit  in New Zealand

-GOS (Galactooligosaccharides) Derived from Milk

-XOS (Xylooligosaccharides) Derived from the cobs of corn 

We saw all types of amazing benefits including a 40% increase in diversity in the microbiome! Which is one of the most important measures of how resilient and healthy your microbiome is. We saw an increase in keystone bacteria that exist in the large bowel that are highly protective against chronic illness. That was all with the combination of the probiotic and the prebiotic. You can buy amazing prebiotics HERE to help rebuild your gut health!

What Bacteria Do These Prebiotics and Probiotics Have an Impact On?

The most important ones are:

Akkermansia: It is correlated with everything under the metabolic syndrome spectrum. Including 60 different diseases and you can also reverse type 2 diabetes with it. We saw an 100 fold increase of Akkermansia in the gut in 3 weeks of adding in the prebiotic and probiotics. 

Faecalibacterium: It protects against inflammatory conditions in the bowel including IBD, Crohns, and even Cancer. 

Bifidobacteria: Helps against Chronic Disease.

Ruminococcus: This is correlated with inflammation in the skin including acne. 

These are important and you won't typically find them in probiotics on the shelf. They have to live in the gut and the moment they are exposed to oxygen they die. You can't grow them outside of the gut in a factory and then reintroduce them. We have to find natural ways of increasing them (including taking our spores!)

What Are Your Thoughts on Dead Bacteria and Akkermansia?

Dead bacteria can have a benefit. They don't fit the scientific definition of a probiotic so they have a different name, Metabolic Response Modifiers or Biological Response Modifiers. Some are very well studied such as Lactobacillus Rhamnosus GG. This bacteria works better in terms of modulating an immune response in the body when it is dead. 

Another one is BLP1, it improves metabolic response in the body which can be useful for weight control. They don't sell it as a probiotic but it has an important benefit. There is something on the outer cell wall or membrane that binds to immune receptors and stimulates an immune response within the body. Here are some theories of why dead bacteria help:

Microvesicles: Bacteria have tiny nano capsules that they can put peptides and neurotransmitters in so that they can release into the environment. Those nano particles go to different parts of the body. These particular ones have an impact when they are dead compared to when they are alive. 

Micro RNA: They are fragments of RNA that can enter your cells and change your gene expression. That is also one of the ways in which plants can impact our health. It's not just that the plant is healthy but the plant contains numerous types of MicroRNA that can change some of our gene expressions. It is considered to be intra kingdom communication. If you remember your classification systems for all living things:

-Kingdom-

-Phylum-

-Class-

-Order-

-Family-

-Genus-

-Species-

The kingdom part separates all of the living organisms into larger groups: mammals and plants. Completely different biological entities. BUT MicroRNA is a way for these different biological entities to communicate and influence one another. 

The limitation of dead bacteria is:

1. It is really strain specific. The Rhamnosus GG strain has this effect but if you use normal Rhamnosus it won't have the same effect. If you are looking for a product to benefit from the Rhamnosus GG effects then you need to look at the species level identification.
2. It only has an effect as the bacteria and the components are passing through your system. The moment you stop taking the bacteria the benefit will be gone. 

Akkermansia in dead form is interesting because a lot of the metabolic studies show that you need live Akkermansia and the dead form does not give you the same benefit. BUT why would you need dead Akkermansia if you can just grow your own Akkermansia within your gut with the right prebiotics and probiotics?

If There Was One Thing You Can Do For Your Gut Health, What Would it Be?

Take the Megaspores! We did a study on people with an inflammatory form of leaky gut and they didn’t do anything different while they were taking it. They didn't change their diet or behaviours and just by taking the spores for 30 days, it completely resolved the leaky gut and all of the inflammatory effects that came along with it! We also did a triglyceride study with people that had elevated triglycerides levels. They took the spores for 90 days and their triglycerides fell far more than they would with any fish oil or prescription product. It is not a miracle product but it affects the diversity and the production of certain post biotics in the microbiome. It speaks to the power of the microbiome to heal. If your microbiome is diverse, resilient, and doing the things it's supposed to do for human health and wellness then you will be fine! If your microbiome is hurt (most peoples are because of our toxic environment!) then we will be more prone to disease. 

Having a sensitive gut can lead to a plethora of different diseases. It is the driver in many chronic illnesses including diabetes, Alzheimers, inflammatory conditions, and more. The most important thing you can do for your health is to build a resilient gut. We have adapted as humans throughout time because we had resistant guts and could eat almost anything. Build up your gut health to reap those benefits once again. Remember to get some spores into your system! Share this with a friend that could benefit from this knowledge.