Mitochondria and the Gut Health Connection

Did you know that your mitochondria have a massive impact on the health of your gut microbiome? I had the pleasure of speaking with Roland Pankewich. He is the CEO of Health Optimization Practice Canada and has a passion for Mitochondrial health. Read on to learn about the connection between Mitochondrial health and your gut microbiome, 5 tips on how you can improve Mitochondrial function, and why we have recently seen so much dysfunction inside of the gut.

How Did You Get Interested in Mitochondrial Function and Gut Health?

My mentor, Ted Achacoso, said to me that the most valuable thing in the world that someone can share with you is perspective. I would like to be someone that shares perspective with people. I have always been interested in health and wellness. I was a high-level martial arts athlete, I had a background in exercise mechanics for many years, and I used to fix broken people from a physical perspective. When I would help people with exercise, they would ask me for advice on nutrition. This is when I started down that path.. 

Once I graduated school, I knew I wanted to see more of the clinical side. I studied functional medicine and I started podcasting and started interviewing people with great perspectives. I learned a lot and then I had an interview with the owner of Health Optimization Practice. He said I was going to bring it to Canada. Which is what I did in 2017.

We are the sum of our inputs. If you imagine the human body as a robot and it has all of these inputs most of them external and some internal. The sum of our inputs should be harmonious. The tone of that harmony should be the tone of health. The output is the manifestation of health. How you see it, how you live it, when you look at someone and you think “I want to know what it is that they do.” That is the health and wellness addiction I want to put out to everyone.

What Are Mitochondria?

There is one thing that everyone knows when they hear mitochondria, the powerhouse of the cell. Since 1957, this is the main thing that one associates with Mitochondria. To break that down further:

-It is the organelle, it's a structure inside of the human cell that takes the proteins, carbohydrates, and fats that we eat and converts it into the cellular energy currency (ATP) through a series of enzymatic steps (both with and without oxygen.)-

Imagine you are eating a sweet potato... once you start eating it and the digestive process has been facilitated, those compounds are being transferred to the cells. This is because energy is needed to function at an optimal level. Without this energy, the cell cannot do what it needs to do as a cell...It cannot divide, output various compounds, and it can't operate in its specialised nature. The mitochondria are the thing that power-up the cell. It also has other functions such as:

-It senses any external threat to the cell (the cell danger response) For Example: When a pathogen or virus is trying to get access to the resources of our cells, it’s the mitochondria that sense it and turn a switch inside of the cell to make it inhospitable for that pathogen to survive

-They regulate cell life span via autophagy

-They regulate calcium metabolism inside the cell

-Factor in Epigenetic control

The health of a cell is down to the health of the Mitochondria. The health of all future mitochondria is directly correlated to what you do to them or subject them to based on:

-Your lifestyle

-Diet

-Activity factor

-Thoughts and Emotions

Overall, they are in charge of making sure the cell can function optimally!

 

What Are Your Thoughts on Mitochondria and the Production of Matrix Water?

The mitochondria can differentiate between deuterium and normal hydrogen. We have been producing our own deuterium depleted water long before they knew that there was another way. If you want to optimise the process, then optimise the inputs so your mitochondrial function can function optimally vs too many free radicals. For extra help, you can also buy deuterium depleted water HERE to help optimise mitochondrial function. 

Heat and Mitochondria

If you look at people that have chronic low body temperature such as people with:

-Thyroid Issues-

-Chronic fatigue syndrome-

There is always a Mitochondrial connection. If there is mitochondrial dysfunction, then the electron transport chain does not flow efficiently. The uncoupling proteins are what detach electrons from that gradient that increases heat production; it doesn't work so well. This means that fat metabolism will be compromised because the only way you can burn fat for energy is through mitochondrial function. That is why it is important to figure out the root cause of these issues. 

How Does The Defense Mechanism Work In The Mitochondria?

The mitochondria are always speaking back and forth with the nucleus of the cell to check-in. This is something that makes major calls in terms of changing the internal status of the cell:

-Do they make it more oxidised?

-Or more reduced?

Reducing agents are attractive to things like viruses and pathogens because they want to utilize the resources inside the cell to replicate their own DNA. A virus will insert its DNA into the nuclear DNA of our cells and it will use the resources to sustain itself. That is not health-promoting to us. This danger response initiates from binding mechanisms. There are two main Pattern Recognition Receptors that get triggered.

Damage Associated Molecular Patterns (DAMPS)

Pattern Associated Molecular Patterns (PAMPS)

Bacterial antigens can bind to these receptors inside the cell and this binding is also initiating a response. If the cell is sensing a threat and the threat is going to have the resources of the cell be consumed for something else’s benefit, the mitochondria will start spitting out reactive oxygen species. It will oxidise the cell which will take energy away from the cell to build compounds that those viral or bacterial factors could then use for their own resources. It is responding to an external threat.

Imagine a movie...You are inside an army camp and there are cameras and motion detectors on the exterior. When something trips them, the alarm goes off and all of the troops are going to their positions. 

This is the same pattern that is existing inside of the cell. The mitochondria are responsible for changing the internal status of the cell. If a cell is more oxidised, it is a more inhospitable environment for anything to live in. The cell will either 1. choke out the virus or pathogen or 2. the cell will commit suicide via apoptosis to prevent the spread of the viral pathogen into other neighboring cells. It will communicate with other neighboring cells and they will initiate the same program as well.

When you think about the body, it’s a story of microbes. You have the mitochondria, which are a colony of archaea (ancient microbes) that are living in the cell. And they have now become organelles within the cell. Then you have the microbiome that is full of microbes as well. -Kriben Govender

The mitochondria also change the activity inside of the cell... The ribosomes are going to be building protein. Some structures are being built and the mitochondria will oxidise the cell enough to have those broken down so the cell will go catabolic. It stops the growth process, initiates the breakdown process, and as a result, it will attract immune cells that will go to the site of that infection and “help gobble up” some of the damage. 

A lot of the immune cells have their own mitochondria as well. If the danger response is being initiated, then it is changing the default state of the immune system to be more reactive. They may be raising:

-TH1-

-TH2-

-TH17-

This will direct certain immune cells to make higher levels of cytokines (inflammatory signal molecules.) This will put your body on high alert. It is a specific and nonspecific response and it is what is happening with an autoimmune disorder or any type of inflammation. Just imagine if this inflammation is localised to an organ….. This organ is going to become dysfunctional to a degree because an organ is nothing more than a collection of specialised cells.

What Are Reactive Oxygen Species (ROS)?

Reactive Oxygen Species is a fancy way of saying it has an unpaired electron, also known as a “free radical.” These electrons are unpredictable in their behavior. Because they crave an electron, anything they touch they steal an electron from it and leave that thing with an unpaired electron. Another way of thinking of a free radical is a compound that is a signaling molecule. The signal or message promoted is oxidation. 

One of the main concepts inside of the cell is called REDOX (Reduction and Oxidation balance). In a healthy cell, they can oxidise and reduce at will because it is always going to be making reactive oxygen species via mitochondrial existence. The main purpose of reactive oxygen species is signaling molecules. If there are too many of them and the cell has enough antioxidants, then it will try to bring it back into balance. 

In some cases, the mitochondria and series of them (there are up to 1,000 in a cell and muscle, liver, and brain cells have the highest concentrations of mitochondria in their cells!) will overly oxidise in response to a threat of its internal environment. This will happen if something causes the cell to not be able to function. That cell will oxidise to destroy whatever is trying to inhabit it OR it will try to kill the cell to contain what is in there via apoptosis. 

There are two ways of cell death:

-Apoptosis- which says “initiate self destruct but don't damage anything peripheral”

-Necrosis- is the opposite, it will affect all of the other cells next to it and may cause them to become overly oxidised as a result

The free radicals have a double edge sword. They are great signaling molecules, this is how the mitochondria communicate with the nucleus to correlate energy status in the cell….. BUT in high quantities, it overly oxidises the cell….

Think of a car that starts to rust: If it rusts on the surface it is just a little cosmetic. But if the rust enters deeper, then the integrity of the car becomes compromised because the metal is now weakened. If you get into an accident the car will fold in half. This is the same thing that happens in the body. You can buff a little bit of rust here and there. But if it goes in deeper, then you know that the tissue is becoming damaged because the health span of that tissue is shrinking.

The Mitochondria and ATPase?

The mitochondria's goal is the ability to create energy to promote cell optimisation of all of the functions. It does this through a gradient. It is the difference between a positive and negative charge and it's the energy potential of the gradient. This means that if the inside of the matrix is negatively charged, and just outside of it is positively charged, it is the protons rushing through this motor that initiate the spin. That is what is powering it. This spin is doing nothing more than combining:

ADP + Organic Phosphate

It smashes these things together then spits them out….It throws them into the cell to be utilized by anything that requires energy to do work. The motor is being turned to generate currency for the cell. That currency is being gobbled up by the cell to perform work.

We focus on the process of aerobic respiration because this is what mitochondria are meant to do. You have cytochrome proteins including:

1st Cytochrome

Complex 2

Coenzyme Q10

3rd complex

Cytochrome c oxidase

5th complex ATPase

The electrons that come in from the Krebs Cycle are being passed across these cytochrome proteins. For every electron that comes in, a proton gets pumped out because the body likes balance. The whole goal is to get the energy potential to spin the little rotary engine to get ATP. Most people know aerobic respiration via glucose…. When the body does this you make 38 ATP. If you look at the other side of it, your body can also burn fatty acids which yield about 109 ATP! It is a lot more energy efficient to be burning fat for energy predominantly instead of carbohydrates.

To a degree, your body doesn’t care what it turns into energy. Fat and carbohydrates both get turned into the same molecule that enters the Krebs cycle. That spits out electrons which run the electron transport chain in the mitochondria. The goal is to make this process run very efficiently. Free radicals get formed when electrons don't go down the gradient. They leak out at specific cytochrome sites (most commonly the first cytochrome.) The problem is, when this electron leaks out and combines with the molecule of oxygen, you get a reactive oxygen species. That thing can go around and oxidise whatever it is touching.

If someone is experiencing high levels of ROS, it just means that the gradient in their mitochondria is very inefficient. There may be a:

-Protein assemble issue

-The membrane itself is too porous

There is a spinning motor inside of the mitochondria that produces an energy currency that the body uses. If this whole process is not functioning properly, we are going to see dysfunction in mitochondria which are present in all cells except for red blood cells. -Kriben Govender.

What About The Gut Microbiome?

The gut is the last line of the body. Every cell in the gut has a high concentration of mitochondria. Because those cells are important for:

-Absorption-

-Mucosal production-

-Creation of Immune Cells-

The mitochondria in the GI system, the cells themselves, are the direct interface with the rainforest that is our microbiome. Those mitochondria can influence the mitochondria systemically through the activation of different genetic transcription factors such as:

-PGC 1Alpha-

-AMPK-

-SIRTUINS-

What happens locally, affects the body systemically. Nothing is truly separate even though medicine separates into different sections of the body, what affects one thing affects everything!

 

Why Do We See So Much Dysfunction Showing Up In the Gut?

“All disease begins in the gut.” It is the last interface with the outside world. If something from the outside world is becoming a problem via an input signal, or if the microbiota has become unbalanced, then that will drive an inflammatory response or a disharmony inside of the gut. This will then affect everything else in the body….because there is a paradox of the GI system. If it were meant to be a rigid barrier it wouldn't be constructed as it was. It is meant to be an absorptive system first and a barrier second. 

If you look at how the gut is constructed, you will see that there is only one layer of cells that is between the absorptive surface (lymphatic system and the bloodstream) and then the gut itself (the tube). The reason that we see things show up early in the gut and later on downstream, is that the result of the inflammatory response in the gut got through the poorly constructed barrier and got into the general circulation.

When something gets into your bloodstream it goes systemically. This is why leaky gut can be the tipping point to a lot of other diseases because it involves the immune system. This prebiotic is a great way to help improve leaky gut! The purpose of the immune system is to either hurt or heal. It is the only system in our body that can do both. When we make our gut mad we make our immune system mad because most of the immune cells reside in the GI system (because of how big it is!) If you took the GI system and flattened it out it would be a couple of tennis courts worth of surface area.

This also requires a lot of policing because the immune cells reside there and they have a lot of ground to cover. This is why we see something show up in the gut before it shows up somewhere else. That can be said for a lot of diseases.

The gut is like a massive interface to the outside world, it is a barrier that is trying to absorb nutrients but then trying to keep out things that can harm the body. -Kriben Govender

The gut cells are bound together with proteins. These proteins are porous; they are meant to let nutrients through. But if these tight junction proteins, due to an inflammatory state, start to become compromised they will:

-Start to not construct themselves properly

-The really tight space starts to let other things fall through the gap

-Which goes to the bloodstream and initiates an immune response, because it was likely something that was never meant to get through the tube. 

We have an ecosystem that is a postnatal organ. We are inoculated when we go through the birth canal. Our microbiome develops on the exposures to things we put in our mouth and nasal cavity. Then the development of that is dynamic based on different factors. The whole goal of gut health- microbiota development is that you want to create a microbiota that helps create a symbiotic relationship with the host and the mitochondria that live in the cells. That wheel of us, the microbiota, and the mitochondria determines if the body is in a healthy state vs an inflamed state.

It is that harmony between these microbiotic cultures that are living in our bodies. The mitochondria within the cell and then the gut microbiota which is a diverse range of bacteria, protozoa, fungi, yeast, archaea and viruses. It is this harmony between these two but then also hopefully protecting the host because that promotes their own survival agenda. -Kriben Govender

For example: When you are creating a space you want it to have well balanced energy that you would want to spend time in. A microbe wants the same thing. It wants to live in an environment that it can adhere to, get enough food and that it has a harmonious environment with the other microbes that live there. The problem we are running into is that people with healthy guts are unicorns. We have to capture them, study them, and see what it is they do because the vast majority of people come to me for gut-related issues which leads me to test to see if they have: 

-Bacterial infections-

-Yeast Overgrowth-

-Inflammatory Protein Upregulation-

-Digestive insufficiencies-

There may be other things that show up as well that let me see an unbalanced gut. People see all of the commercials for the antacids, GI issues and they take them. That is a sign that something is wrong! You need to figure out what is wrong and how to remove it in the first place.

How Does The Gut Microbiome And The Mitochondria Communicate With Each Other?

They can communicate bidirectionally. The Gut Microbiota creates these metabolites that can affect the health of the cells. For example:

-They can create lactic acid, that can be converted into something that the mitochondria can use for fuel. 

-They can create short-chain fatty acids (butyrate, acetate) that can directly enter the colonocytes

-They can create things called Urolithins which improve the ability for the mitochondria to stimulate the biogenesis process. This increases the concentration of mitochondria OR the health and wellbeing of them

As a result of the microbiota producing these compounds, they can influence the healing of the gut barrier. They can also influence how robustly the mitochondria take the food inside of your cells and turn it into energy. Then this can influence the body to make it better at turning food into energy and less adept at turning the food into body fat. 

Mitochondria can affect the gut barrier function and can influence the health of the gut microbiota by:

-Spitting out things like reactive oxygen species

-Changing gut barrier function

-Creating a scenario where an inflammatory response or a dysbiosis can show up because of the dysfunctional gut barrier itself.

They have back and forth cross talk. The status of the cell will affect the gut barrier and ultimately influence the microbiota and the dynamics between them. 

How Do the Gut Cells and the Bacteria Benefit From One Another?

If the bacteria in your microbiome are breaking down adequate amounts of soluble fibres that come through diet, then they are creating short-chain fatty acid compounds that can diffuse the mucosal layer. They will then go directly into those enterocytes and feed them. The bacteria living in our gut, providing that we create an optimal environment, will then produce food for the colon itself. The bacteria will break down these fibres and it will use the creation of those fibres to improve the environment to foster healthy gut bacteria. 

An acidic environment is an environment that yeast does not grow in very well. So the colon should be an acidic, oxygen-free environment, so we have a lot of diverse anaerobic bacteria. That is also dependent on the gut cells making a nice physical barrier. In the colon for example, we have a submucosal layer:

A thick layer of mucous

The cells

A watery layer of mucous

The bacteria 

The goblet cells are secreting mucus constantly and they require strong mitochondrial function for that mucus to be constantly synthesized.

Other specialised cells influence the turn-over of those enterocytes. Your digestive cells turn over every 3-5 days. You want to have this innate stem cell that needs to be powered up to differentiate the different cells. It requires the mitochondria to be fed a direct stream of the short-chain fatty acids (Or glucose coming in from your diet!) They can't do this without each other. The bacteria have to be there to power up the colonocytes to maintain the gut barrier function, and the enterocytes have to be there to create an environment for the microbiota to live in. We are all trying to strive for balance and symbiosis.

How Do We Improve The Function Of The Mitochondria?

I can’t measure a lot of these pathways but I can assume things based on how the pathway is activated. For Example: If someone is looking at how to optimise mitochondrial function through diet, you know that metabolic flexibility (the ability to burn carbohydrates or fats) is a big thing. Someone who has metabolic dysregulation, such as Type 2 Diabetes, you know that there is something that is not functioning or flowing smoothly. From the food choice, to the digestion, to the absorption, to the utilization process. Here are 5 ways that you can help improve the Mitochondrial function:

1. Restricting the time feeding window that you give yourself. When you do this, you force your body to turn over to stored energy (fat cells) This can then shift the body back into a state where it can burn fat as a predominant source of fuel. Not only do we regulate the hunger signal by tapping into it, there are some elements of that that become anti inflammatory. Constantly feeding the body is like constantly shoving food into a kitchen… There is only so much food that can be cooked before the stove is full or you run out of power. 

2. Look at what cofactors are needed to create energy via the mitochondrial oxidation process. 

To turn carbohydrates into energy, you need:

-Vitamin B1

-Magnesium 

-Vitamin B2

To turn fats into energy you need:

-Vitamin B5

When it comes to this cycle you need all of these cofactors: vitamin B1, B2, iron, sulfur, and manganese. If you aren't getting them from your diet you may have all of this energy coming in the form of macronutrients but your micronutrients are deficient. Eating a more micronutrient dense, energy sparse diet, is going to make sure you have the right balance of both nutrients for that process to be taken care of.

3. When you look at disposal, certain things cause the mitochondria to uplevel their process such as:

-Walking outside on a nice day

And you are using fat as an energy source (if your blood sugar is balanced). If you really want to push your mitochondria you can do:

-Resistance Training

-Interval Training

-Short Duration Sprints

These all activate your anaerobic system which starts your aerobic system to power up those energy stores so you can do it again and again. You are looking at the input and the output levels and you want to see how you can optimise them through diet, lifestyle, sleep, and activity.

4. When it comes to the GI system, it all starts with the digestive process. If you don't:

-Chew your food enough

-You're not relaxed enough to activate the parasympathetic nervous system

-You aren't making enough stomach acid

-You aren't making enough enzymes or bile (you can buy enzymes HERE)

Then that food is not going to get properly digested. Then it won't be properly absorbed. If you dig a layer deeper, you have to look at the food choices themselves. high starch low fibre, high sugar foods are great at supporting the overgrowth of yeast and pathogens(not good!) Especially if someone has a history of antibiotics. 

5. You have to make sure that you get adequate amino acids. The mucosal layer, and where the bacteria live, is very amino acid rich. Choose different kinds of plant foods that vary the types of fibre, phytonutrients, the starches that feed the bacteria. You can also buy this Collagen Peptide powder which is full of amino acids!

For Example: When I go to a restaurant, in my head I have an instant analysis of the items on the menu wondering “what micronutrients are in here, what fibre, what will it do to my blood sugar?” I make my choices based on this. Next time you are out, try to see how many different foods you can eat! We don’t know what food bacteria eat but if you eat various fibre and micronutrients, you are likely going to be better off than the majority of people out there that just eat for convenience.

What Is Hormesis?

Hormesis is what stimulates the body to be more dynamic and its ability to thrive under certain conditions and scenarios. 

A specific example of this is: Intermittent Fasting. You are subjecting your body to a stressful condition in which the response to that stress will yield a positive solution. Fasting is a way of coming off of the energy input assembly. No energy is coming in but the body still needs the same amount of energy to sustain itself. It changes the influence of how your cells have to perform. If we are not ingesting food, then we know that we have stored energy that is sitting on our tissues (body fat!) for the body to use.

The hormetic stress of fasting is going to upregulate the enzymes and the endocrine system to be better at:

Breaking fat down from storage

Delivering that fat to the cells

Metabolizing that fat for energy

You restore metabolic flexibility from fasting via hormesis of fasting itself. 

Another example is cold exposure, or heat shock via a sauna. Exercise is hormesis BUT as with anything, you want to make sure that it is an appropriate stress for you. For example, if someone who is hypoglycemic wants to do a 24 hour fast… this might not be a good idea. You might want to start with something like 8 or 12 hours. Or for someone who has chronic fatigue syndrome might not want to do cold exposure or go into the sauna. 

It is choosing a sensible stressor to challenge the body and elicit metabolic flexibility  -Kriben Govender

Antioxidants are hormetic stress to the cell because they cause a reduction stress that forces a cell to balance out the reduction of oxidation. An antioxidant is a very mild stress that improves the antioxidant defenses of the cell. By eating colored vegetables you are technically doing hormesis. They influence the change in microbial diversity. 

Mitophagy vs Mitochondrial Biogenesis?

Mitophagy is mitochondria specific autophagy. Which is a process of the recycling of old worn-out material to repurpose for building new material. It is a way for the cell to reuse resources that may be old and worn out and under-performing. For mitochondria, they can go through mitophagy and it may involve clearing out old dysfunctional mitochondria that might have too many reactive oxygen species. They then divide, fuse together, and they birth new mitochondria. Mitophagy can also donate materials to Mitochondria Biogenesis which is the creation of new mitochondria to suit the increased energy requirements of the cell. 

An Example: you can engage in Mitochondria Biogenesis through exercise. That is why endurance athletes are so good at aerobic exercise because they have a lot of mitochondrial density in their muscle cells. The constant (good!) stress of the body makes them more adaptive to this. They will increase the number of mitochondria in the muscle cell via mitochondrial biogenesis. The body will break down old worn-out mitochondria via mitophagy so you don't have dysfunctional energy organelles in the cell.

If you keep telling your body, through exercise, that you need to be able to produce a lot of energy, then the body is going to respond by making you better at producing energy. It is an adaptive mechanism within us to better suit our environment. 

What Was A Challenging Client Issue You’ve Gone Through And How Did You Go About Helping Them?

1. I was working with a colleague and one of her clients that we were working with was experiencing distress. It was a combination of GI distress and the inability to metabolize energy properly from a body composition and an energy metabolism perspective. I ran some testing and we saw that there was:

-Yeast overgrowth

-Dysbiotic bacteria

-The inability to burn fat for energy effectively

We then combined: supporting energy metabolism, supporting GI health (managing the dysbiosis) and helping to build a better microbiome through removing specific foods and supplementation. In a matter of 11-12 days they dropped 11-12 pounds. This changed how they looked, how they felt, and their energy levels. 

2. I have a client who had a combination of chronic anxiety and fear that enabled her to  leave the house without knowing where every bathroom was within a square kilometer radius of where they were going. She is now at the point where she goes to the gym and this reset totally changed her mindset, her career, and she said she got her life back. Before we helped improve what was wrong she had:

-Mitochondrial dysfunction 

-Inability to regulate energy metabolism

-Overgrowth of yeast

First, you balance out things in the system and then you restore the body's ability to optimise its function and maintain health. Your body doesn’t know how to disease itself, it's what we do to it that does it. 

I am a firm believer that it all comes back to nature. We are all trying to understand the mechanisms of how these things work then adjust it but it always seems to go back to the body's innate intelligence and how we naturally evolved.-Kriben Govender

A lot of the things that we implement to get someone in better health, is mimicking what the body is optimised to do. The sun, the circadian rhythm, and stress management all play a massive role in maintaining our health long term.

If There Was One Thing You Could Do For Your Gut Health What Would It Be?

Eating in a relaxed environment! Focusing on being mindful in the process of eating and chewing thoroughly is the easiest thing that you can do to optimise that experience. Make your mealtimes a sacred time. Your body will digest the food how it is supposed to and the downstream effects of everything will yield a better outcome. 

Make sure that you have enough fibre in your diet, make your gut health a priority, and follow the 5 tips on how to improve your Mitochondrial function today. Even reducing stress can have a massive impact on how your body handles day to day life. Share this with a friend or family member that could benefit from this information!