Kiran Krishnan: Gut Health Secrets for a Stronger Immune System & Better Skin
Today we are joined by Kiran Krishnan, founder of Microbiome Labs for a fascinating conversation. Kiran shares his insights on a wide range of topics, including the interaction between the microbiome and the immune system, the impact of antibiotics on gut health, the gut-brain interaction, and the connection between gut health and skin health.
Who is Kiran Krishnan?
I have been obsessed with science, math, and understanding the world around me since I was a little kid. My parents have a nice mix because my dad was an engineer and my mom's a medical doctor. So I grew up with both sides of the world of science. I parlayed that mix of having a little bit of both of them into the world of microbes. I got into microbes because I have always been fascinated about the unseen world whether that was exploring dark matter and all kinds of subatomic particles or subcellular life.
I gravitated towards microbiology and as I was coming out of academic research and looking for where my area of interest lay, the Human Microbiome Project started kicking off. It became clear to me that that was an area that was very much pioneering in health, wellness, and how we function as humans. I dove into the world of the microbiome and a few years later I created Microbiome Labs as a way of rethinking and retooling a lot of our old ideas around gut health, probiotics, and prebiotics.
I also support practitioners and health-minded people with tools to effectuate the microbiome and gain health. Teaching and education is another area of interest for me and the one skill I have is explaining complicated things to people in a way that they can understand. That is a big part of what I do on a day-to-day basis.
How Do The Microbiome and Immune System Interact?
So how do the microbiome, the gut, and the immune system work together to keep us healthy? This is an important topic because not only does it protect us from disease, but it is also equally as important from the perspective of tolerance. We want an immune system that reacts to the right things. More often than not, we have immune systems that are attacking things they shouldn’t and that is where things like allergies, asthma, food intolerances, and autoimmune conditions come from.
The simplest way to explain the relationship between the immune system and the microbiome is that it is two parts of the same system. The microbiome acts as the eyes and the ears of the immune system. So imagine that your immune system is a military that was created in your system with all of the equipment necessary to defend the system. You have the T cells, B cells, and other tools to defend the body. The problem is that it doesn't have a general and has no information about who the enemy is. The reason why the immune system is born naive is because we're constantly producing new immune cells. Humans are adapted to live in many different environments and each environment is going to impact the immune system differently.
If the immune system had a fixed code telling it exactly what to attack and what to ignore, it would lose its ability to adapt to changes in the environment. And that adaptability is exactly what we need. If I come to visit you in Australia, I want my immune system to adjust to what’s happening in your environment instead of just operating based on what it knows from Chicago. That’s a key function of the immune system that people need to understand - it’s constantly learning, assessing its surroundings, and determining what’s a threat and what’s not.
But at the same time, the immune system doesn’t have an outward-facing component. We don’t have immune tissue on the surface of our body actively sensing the environment and the microbes we come into contact with. So the immune system has to get its information from somewhere. As it turns out, it gets this information from the microbiome.
So why does it get the information from the microbiome? It is because the microbiome is loaded in all areas of the body where we gain the most exposure to the outside environment. For example, the digestive tract is where we expose ourselves to the outside environment from everything we eat, drink, and breathe in. When you take a breath, all the particulate matter gets caught in the mucus in your upper and lower respiratory tract and is then moved up through the respiratory tract through the mucociliary elevator. These are hair-like structures that move the mucus up and then you end up swallowing it.
Everything that drains from your ears and eyes then drains to the back of your throat through the eustachian tube and then you swallow it. This means that everything you're encountering ends up in the digestive tract. Things also can go in the urogenital tract and through the skin but no matter what it is entering into a mucosal surface and most of the mucosal surface in your body is loaded with microorganisms. And these are the commensal microorganisms, assuming you have a healthy microbiome.
The microorganisms have the capability of dealing with many of these things that you encounter on their own - even if it is a toxic, virus, or bacteria. At the same time, the microbiome then sends signals to the immune system to recruit it and show what it has encountered. The reason why the microbiome has to recruit the immune system is because the immune system is outnumbered by microbes 200,000:1. For every immune cell that we have roaming around and monitoring the system there are 200,000 microbes.
Keep in mind that a set of things that the immune system is supposed to protect you from are microbes so being outnumbered is a very difficult task for the immune system. The only way it accomplishes that is because most of the other microbes are working with the immune system to alert it when something is off. So imagine an immune system where there isn’t a microbiome - it would either not react to anything or react to everything it sees including the host tissue. Those are the two extremes of what happens with immune systems that don't have a companion in a working microbiome.
When you think about the cold and flu that tends to show up in the winter months, it’s crucial to understand what happens when you breathe in the influenza virus. The virus enters your respiratory tract and targets your lung cells, beginning its infection there. The microbes in your lungs are the first to notice this invasion. They recognize that something is off and start responding by releasing compounds like interferons (like interferon gamma) to slow down the virus’s replication in that area. At the same time, they send out signals to recruit the immune system to the site of infection.
If the microbiome can keep the infection in check while calling in the immune system, you might feel a bit tired or under the weather for a day or so but then you’re fine. But for individuals with a compromised microbiome that isn’t supporting the immune system, the response is different. The virus enters, starts replicating unchecked in the tissue, and the body struggles to mount an effective defense. Your microbiome looks at it and goes “Eh I don’t really care. I am not here to work with the host” and then the virus keeps replicating. Then the infection gets bigger and bigger and once the immune system notices it then it has a much bigger problem to deal with. This is when you start to feel really under the weather and have symptoms like:
- A high fever
- Fatigue
- Body aches and pains
This is all the response of the immune system to a larger-scale infection. But when the microbiome isn’t functioning properly, it fails to bring in the adaptive immune response, the more powerful line of defense. As a result, that response is delayed, leaving you feeling sicker for longer. It takes much longer for the adaptive immune system to finally step in, start controlling the virus, and produce antibodies against it. Recovery can drag out for about 10 days.
On the other hand, someone with a healthy, well-balanced microbiome might feel slightly under the weather for a day or two before bouncing back to normal. Whereas an individual with a compromised microbiome will start feeling significantly worse after three or four days, deal with severe symptoms for six to seven days, and then take another three or four days to fully recover. The key difference between these two individuals is the presence of the right types of microbes in their system.
When the microbiome is already dysfunctional, it becomes much harder for the body to handle infections. This was especially evident during COVID-19. For example, a 48-year-old with diabetes had a tenfold higher risk of dying from COVID-19 compared to a 48-year-old without diabetes. The underlying issue? Dysbiosis - an imbalance in the microbiome that not only contributed to diabetes but also weakened the immune response.
How Does The Microbiome Identify Friend and Foe?
The most common way in which the microbes in a given local area signal the immune system is by using inflammatory cytokines like:
- Interleukin-6
- NF-kappa B
- Interferons
And they shoot those off in the local area which becomes the alarm for the immune system to go quickly to that spot. But people with chronic conditions or underlying co-factors like diabetes, obesity, heart disease, and autoimmune conditions, are all hallmarked by having chronic low-grade inflammation. These individuals tend to be inflamed throughout their body all the time, which means that when the microbes shoot off the inflammatory cytokines for the immune system's attention, it is more difficult to notice those cytokines because there's inflammation throughout the body already.
This is another way the immune system becomes compromised - signals from local microbes trying to recruit the immune system to the infection site get drowned out by the inflammation already present in the body. Leaky gut is also one of the most common drivers of chronic low-grade inflammation. When someone has a leaky gut and widespread inflammation, it becomes much harder for the immune system to focus on the right target, making it less effective at responding to new infections or infections in general.
Is it Better to Expel Phlegm or Swallow?
When we have this mucosal reaction pushing up phlegm, trapping bacteria, typically what happens is we get told to take medicine to expel this phlegm and mucus out of the body. And then typically what happens is you cough, you expel the phlegm, and then you spit it out. So is it better to swallow it so it gets down into the heart of the immune system, which is the gut, to train the body, or is it better to spit it out? -Kriben Govender
This highly depends on the amount of mucus because you can certainly swallow enough that it upsets your gut. People who have chronic sinusitis build up so much mucus and constantly have post-nasal drip. This can cause diarrhea because there are enough bacteria and immune factors and all go into the gut which disrupts the gut microbiome's function.
So you certainly want to swallow some of that but if you have something like bronchitis or a bad lung infection, you will want to expectorate as much of that out as you can. Some of it will inevitably be swallowed - it’s in your mouth, and just the act of coughing ensures that happens. If you think about coughing, there’s a chaotic cloud of microbes being expelled, but not all of it leaves your body. A lot of it hits the walls of your mouth and stays there, eventually getting swallowed along with your saliva.
This process of sampling in the gut is crucial. About 80% of your immune system’s sampling tissue is located in the gut, making it a key site for detecting and learning about potential threats. As these microbes pass through, the immune system starts assessing what you’re being exposed to, while the microbiome helps determine whether these are things to attack or ignore.
Training The Immune System
Tolerance is very important because we do not want the immune system to overreact but we do not want it to underreact. So how does this get regulated? Well, we have a T cell called the T regulatory cell (Treg) which roams the system and looks for aberrant immune responses (responses that your body does not want or need). The moment those immune cells start to respond, the Treg cell sees it and it suppresses that immune response. As a result of suppressing, it helps teach the immune system that this is not something we need to attack. This helps build tolerance. However, the expression of the Treg cell is dependent on microbes. So when you have a healthy and diverse microbiome, the microbiome triggers the proliferation of Treg cells to help regulate all the immune responses. The microbiome can also tag things for tolerance's sake.
So imagine then you have a compromised microbiome with chronic low-grade inflammation throughout the body. If a virus or something enters into an area of dysbiosis, your microbiome in that area is not necessarily helping because they're mostly opportunistic pathogens - so they don't want to bring the attention of the immune system to that area either because they're doing some questionable things themselves. So then your immune system is not alerted and the infection gets worse and worse. Then your own cells start to shoot off cytokines that are getting infected and dying. Lastly, the immune system may see it in this milieu of inflammation so it might end up seeing it at some point but it's going to be delayed and the infection is going to be bigger.
Now your immune system comes along and the innate part of the immune system is the fast-acting early responders but they are not specific for whatever is causing the problem. They just show up to the region and start bombarding everything. It is like they are trying to kill a mosquito with the blowtorch. Yes, you’re going to kill the mosquito but you'll probably burn the wall a little bit behind the mosquito as well. This results in damage to your tissues and cells because they are a bystander in this war that's happening.
Then the adaptive immune system comes along to try to figure out what is causing the problem and what is the specific tool for that one offender. The adaptive immune system shows up as a result of antigen-presenting cells that present the potential culprit to the adaptive immune system - these macrophages and dendritic cells. They show up right after the innate immune system, they look at the debris, and they start gobbling up parts of all the stuff that's out there. Then they keep presenting it to the T-cells and B-cells and say “This might be the culprit”. Then the T-cells and B-cells have to mount antibody responses to all the things that it's showing.
Treg cells play a crucial role in preventing autoimmunity by recognizing when your own tissue is accidentally presented to the immune system. This can happen when there’s a high level of cellular debris in an area due to ongoing immune activity. In the process, macrophages may mistakenly pick up fragments of your own tissue and present them to the immune system. When this happens, a T-cell or B-cell might create an antibody against your own tissue, potentially leading to an autoimmune condition. This is usually prevented by Treg cells, which act as immune system monitors. They recognize when self-tissue is being mistakenly targeted and intervene, shutting down the faulty immune response. But for Treg cells to function properly and exist in sufficient numbers, a healthy microbiome is essential. Without that microbial support, the immune system loses an important safeguard against autoimmunity.
When the microbiome isn’t healthy, the immune system faces multiple challenges. The innate immune response becomes sluggish because there aren’t enough microbes signaling the immune system to the right location. At the same time, excessive inflammation leads to increased tissue damage. As a result, macrophages and dendritic cells start presenting fragments of your own tissue to the immune system. Without enough Treg cells to intervene, the risk increases that a T-cell or B-cell will mistakenly identify your own tissue as a threat and create antibodies against it. This breakdown in immune regulation is what ultimately leads to autoimmune conditions.
This is why people who are susceptible to autoimmune conditions (one of the key susceptibilities is having a very dysbiotic gut microbiome) may end up with lupus after a cold or flu. This is because the cold or flu triggered an autoimmune response and now your immune system is targeting your own tissue and you don't have the microbiome to prevent that from happening.
That is a brilliant explanation of the very complex workings of the immune system and how important a resilient microbiome is. And if you do end up with an infection, to fight it effectively. I certainly encourage audience members to go back to the previous blog with Kiran to explore how to build a robust, resilient microbiome. -Kriben Govender
The Effect of Taking an Antibiotic to Treat Infection
So what happens when we take an antibiotic to fight an infection? Antibiotics are very important, especially if you're suffering, but what happens to the microbiome when you take the antibiotic? Are there both negative and positive aspects of it? -Kriben Govender
So let's tackle viral infections first because this is where antibiotics are most often misused. In the USA the CDC estimates that at least 50% of the antibiotic scripts are unnecessarily written, and that's often for viral infections. And the thinking is twofold here. So if I start feeling run down and have the sniffles and all that, it's more than likely a virus, which means that it has to run its course.
But since we all have to go to work, we might go to our doctor or urgent care for help. An educated doctor or urgent care center will know in their mind that this is a virus and that there is nothing you can do but rest. But in the US we have a for-profit medical system and many of these doctors and clinics are competing with each other. So if I went to one of these clinics and they gave me nothing for it and just said, go home and rest, then I'm less inclined to go back to that clinic next time I feel sick.
Many of the clinics and doctors then feel pressured to write a script for something, even though they know that it is not going to help the patient. The way they rationalize it is sometimes when you have a viral infection, and if the viral infection goes on for a certain amount of time, you can get a secondary bacterial infection as a consequence. So in their mind, they think “Well, I know it's not going to help with this, but maybe it'll prevent a secondary infection so I'm just going to give it to them.” Doctors don't know the type of harm that an antibiotic can have if you don’t need it.
If you start taking an antibiotic for a viral infection, your response to fight the virus will slow down because you're decimating the microbiome. If it is a bacterial infection, the antibiotic will certainly help because it works directly on the bacteria. However, you could revert and get a second infection from that same bacteria because your immune system and microbiome are now compromised.
So there are absolutely times when you need an antibiotic for an infection and it'll save your life but if it is a fungal or viral issue and you are given an antibiotic, it is going to compromise your immune system's ability to deal with it. We now know how important the microbiome is for immune function and this was very beautifully shown in the area of immunotherapy for cancer. There are certain cancers like melanoma and non-small cell lung cancers, where immunotherapy works well. Immunotherapy is a way of getting your own T-cells to go after the cancer cell. Normally, we are all developing cancer-like cells all the time but we have our immune system that detects it and shuts it down (it's typically the T-cells within the immune system).
What they're figuring out is that there's a way of upregulating your T-cells ability to go after cancer tumors. What’s great about it when it works is that it's a very potent treatment against that tumor and there's no other collateral damage because the T-cell is so specific for the tumor. It's not like radiation or chemotherapy that just destroys lots of stuff. Then the re-emergence of the cancer is very low because now your immune system is trained on how to go after this particular cancer. So immunotherapy is great but it counts on the immune system functioning properly for it to work.
Studies show that immunotherapy is far less effective when an individual undergoes a course of antibiotics before starting immunotherapy. This happens because T-cells don’t function properly when the microbiome is disrupted. Research has also found that individuals with high levels of keystone species or greater microbial diversity respond much better to immunotherapy than those with an imbalanced or unhealthy microbiome.
This highlights just how crucial the microbiome is for proper immune function. If we’re going to use antibiotics - knowing they will significantly impact the microbiome, at least temporarily - it needs to be a deliberate decision made for a valid reason. It shouldn’t be a casual choice, like taking antibiotics just because you suspect a strep infection but aren’t sure, or because you’re feeling rundown and just want a quick fix. That kind of overuse is risky. There should always be confirmation that it’s a bacterial infection before reaching for antibiotics.
Strategies to Counter The Negative Impacts of Antibiotics
In 2020 we published a paper where we showed that using the spore-based probiotics (Megaspore) and then adding in the H258 (subtilis at high doses) negates a lot of the negative effects of the antibiotic. This is because the spores are constantly revamping the microbiome and the antibiotics will knock everything down in about two or three hours of ingestion of the antibiotic. So if you take the spores around this time they can revamp the system. They increase lactic acid production, short-chain fatty acids, and remodulate the microbiome from the damage that that dose of antibiotic did.
Once you're done with the let’s say 10-day antibiotic course, if you stick to that same regimen for prebiotics and probiotics (I always recommend three times longer than the antibiotics), so 30 days, you're going to reverse or negate the vast majority of damage that the antibiotic has done.
So if the antibiotic is indiscriminately destroying, especially keystone species, these microbes involved in signaling, then what we're trying to do is bring those levels back up and also introduce some more resilient spore-based organisms that could potentially be resilient to the impacts of the antibiotic. How about something like immunoglobulins, colostrum, or a direct butyrate supplementation? -Kriben Govender
All of these can be beneficial:
- Butyrate which modulates inflammation and supports some of the keystone species. A tributyrin type of product could be very beneficial.
- Probiotic yeast like Saccharomyces boulardii. This can provide a lot of support by producing lactic acid and then as a precursor to short-chain fatty acids.
If you had to go on a course of antibiotics (talk to your doctor and if that's the right decision), then you should throw whatever you can at your system to negate the negative effects of the antibiotics. If you have to be on it, that's fine, it's important, but it doesn't mean you have to suffer from the side effects.
The Impact of Antibiotics on People Around You
Let’s say you were given a course of antibiotics and you just take the antibiotics willy-nilly without doing much to try to support the microbiome. Not only are you impacting your microbiome but you're impacting the microbiome of the individuals that live in your household. There was a study out of Johns Hopkins in 2019 or 2020 where they took individuals who were given a course of antibiotics at the hospital and before starting the course of antibiotics, they did stool testing and mapped out their microbiome. Then they followed their microbiome during the antibiotic and up to six months after.
Now, at the same time, they also mapped out the microbiomes of individuals who lived in the same household as the individual on the antibiotic but those individuals were not on antibiotics. Researchers found that the disruptions in the microbiome of an individual taking antibiotics were also observed, almost identically, in those living with them, even if those individuals weren’t taking antibiotics themselves. This wasn’t limited to intimate partners it also applied to:
-Platonic roommates
-Siblings
-Parents
-Children
-Other household members
This highlights the fact that we exist within a shared home biome. We each carry a personal cloud of microbes, and the state of our microbiome influences the microbiomes of those around us - positively or negatively. That’s why it’s so important to consider microbiome health from a household perspective. It’s an ecosystem we all contribute to, and we all have a responsibility to maintain.
If one person in the household takes an antibiotic without much thought, assuming it’s no big deal because they’ve taken antibiotics before, that decision affects everyone else in the home. And for some, the impact is significant and measurable. This is especially relevant for parents who put effort into keeping their children healthy. If they neglect their own microbiome, they may be negatively affecting their child’s microbiome as well. A healthy household microbiome requires collective care because, at the end of the day, we all share a microbial environment within our homes.
I think a lot of light bulbs are going to be going off in households to be more cognizant of how we use antibiotics and especially how we negate some of the effects. - Kriben Govender
The Gut-Brain Interaction and Psychobiotics
We know that anxiety and depression are at epidemic levels, even in younger kids. I heard a statistic that said that the level of anxiety, psychosis, and cognitive dysfunction in the average high school child today is equivalent to what the average asylum patient was like in the 1960s. So if you imagine the high school kids today, the level of anxiety, depression, ADD, all of the things that they face regularly, those were asylum-level problems just a few decades ago.
Then the question becomes, “What's happening?” We know stimuli are different these days, our phones and social media give us too much access to information. We're certainly surrounded by negative stimuli much more than we ever were and it is hard to escape it. We are also bombarded with a lot of information and triggers nonstop. This all plays a role but I think our resilience in dealing with simple stressors has also gone down quite a bit and that is a factor of the gut-brain access.
If you think about the last few decades, every condition that has anything to do with how the gut microbiome influences the condition - every one of those conditions have gotten worse since we have gone on such as:
-Diabetes
-Obesity
-Autoimmune conditions
-Allergies
-Asthma
-Alzheimer's
-Dementia
All of these conditions can be traced back to some origins within the dysfunctional gut microbiome. They are all getting worse in terms of prevalence and severity because our gut microbiome continues to get decimated as we go along. Our diets and use of antibiotics drive dysfunction.
There are a few roles of the microbiome in this process of anxiety, depression, mood disorders, and cognitive function. The number one role of certain organisms within the microbiome is to stop HPA reactivation. HPA axis stands for the “hypothalamic pituitary adrenal” axis. This is the system that gets activated when we encounter a stressor. That system has not changed in the last 200,000 years and it is designed to trigger a fight or flight response. It’s been a very important thing for the evolution of humans because it's what gave us the smartness to identify dangers and either fight or flee from them.
The problem is that this same biochemistry functioning is now triggered by things like a text message or something we see online. We now have this kind of stimuli all the time and this response causes the HPA axis to release cortisol. Cortisol is a stress management hormone that does several things when it is released:
1. It increases respiratory rate and heart rate while triggering vasodilation to direct more blood to critical areas (primarily the heart, muscles, and brain). One key way the HPA axis facilitates this blood flow is by increasing inflammation. Macrophages and dendritic cells, key players in the innate immune system, are stimulated to release catecholamines which are chemical irritants that promote inflammation. When a part of the body is inflamed, it becomes red and warm due to increased circulation to the area. The same principle applies during a stress response - your body strategically upregulates inflammation in the brain, heart, and muscles to ensure they receive sufficient blood supply. Cortisol plays a crucial role in regulating this entire process.
2. It also gets dumped into the gut then in the gut, it gets metabolized by certain bacteria and the byproducts of the metabolization of cortisol end up in your kidneys. Then your kidneys turn on sodium and potassium pumps and flood your system with fluid. This increases blood pressure, perfusing the system even more. This is why chronic stress creates hypertension because stress is designed to increase blood pressure acutely to increase perfusion. So when you're in a fight or flight response, and if a predator is chasing you, you want inflammation in the brain, in the heart, and in the muscle. You also want elevated blood pressure because you need to be able to get away from the predator. But the last thing you need when you're reading an email or text is increased blood pressure and inflammation in the brain, heart, and muscles. We're not trying to survive anything but we still get that same physiological response.
The problem for us in the modern world is that with the fight or flight response, we’re meant to enter that heightened state when danger arises where cortisol levels spike and activate all the necessary processes. But once the danger subsides, we should be able to calm down and return to a baseline state. Our ancestors experienced this regularly. They would be walking through the grasslands when they spotted a rustling in the grass and their fight-or-flight response would be triggered.
Then they would run from danger, reach a safe spot, and sit down to breathe to get back to their normal state. That’s how it’s supposed to work but if your gut isn’t healthy and you don’t have the right organisms in your gut microbiome, you can’t properly come down from the fight-or-flight response. This is because the microbiome plays a crucial role in attenuating the activation of the HPA axis. When cortisol floods the gut, it creates leaky gut, and as a result, a compound called IL-6 increases. This compound can travel to the brain, reactivate the HPA axis, and put you right back into the same stress cycle, even without any new external stressor.
For the average modern person, it’s a constant cycle. You’re driving to work, running late, and someone cuts you off. That small trigger kicks off the HPA axis, sending you into a fight-or-flight response. Now you’re stressed, but you can’t come down from it because the leakiness in your gut keeps upregulating the stress response. So you get to work, and the first annoying thing that happens there heightens your stress even more. Your tolerance for irritants becomes so low that you’re triggered over and over throughout the day. You stay in a constant state of heightened anxiety or fight-or-flight for the entire day. It’s hard to shut it off because the off switches aren’t functioning properly, and those off switches depend on your microbiome.
This is where psychobiotics come into play. These are microbes that have been identified as commensal microbes with unique abilities to turn off HPA axis activation and bring the system back to its baseline. They produce compounds like peptidoglycans and complex carbohydrates on their cell membranes. When these complex carbohydrates are digested by macrophages, they’re released into circulation, where they help attenuate and stop the reactivation of the HPA axis, allowing the body to return to its basal state.
They provide you resilience but they do not act like a Prozac where they all of a sudden numb. Their function is to be taken every day and then in 30 days or so you'll see that your perception of stress in general is dramatically reduced. This is because it reduces the height of your cortisol curve and also allows you to taper off cortisol much faster. Then you are not constantly being reactivated with the HPA axis because it can shut down your HPA over action.
Psychobiotics play a crucial role in helping you manage stress and build resilience. While stress is an unavoidable part of life, how you handle it is what matters. Your body needs to go through the activation of the HPA axis, come back down from that heightened state, and then repair itself. If you can do that, you're in good shape. Everyone experiences bouts of stress, but the problem arises when you can't come back down from that heightened state. If you don’t reset at night, it affects your sleep, messes with your digestion, likely causes loose stools, and leads to weight gain. It becomes a snowball effect that just keeps spiraling downhill.
I think we can all resonate with what you said. I had a cheeky little smile on my face recounting some past experiences of being irritated and stressed. I think it's just a reality of modern living. Social media is not going anywhere and the level of stress is certainly not going to alleviate. It's just part of the lifestyle that we live in the modern era. But we can use tools like psychobiotics and Zenbiome is amazing. - Kriben Govender
Psychobiotics and Sleep
When you're in a fight or flight response, you are in the “sympathetic” activation. The neurological system has 2 states:
-The parasympathetic state which is the rest, digest, and repair system.
-The sympathetic which is the fight or flight system.
Your nervous system toggles between those two. If you are an average Westerner or modern person living in a city, the likelihood is that you toggle towards the sympathetic side most of the time. Then you have a lot of external stimuli that keep you in that sympathetic state. The problem with the sympathetic state is that it works against sleeping because your body is saying you are in danger. This leads your visual and auditory perceptions to be heightened. You cannot sleep in this state and you need to be able to shift back to the parasympathetic (by releasing things like GABA and melatonin), so your system can shut down.
You need to feel safe to be able to sleep and most people don't biologically feel safe, whether they know it logically or not. Psychobiotics can turn all of that off and bring you back to your basal state which will help induce sleep in individuals who are struggling with sleep.
Stress and sleep go hand in hand - if you are stressed you cannot sleep and if you are not sleeping enough, you will increase your stress. It's a vicious cycle for most people and this is where psychobiotics (like Zenbiome Sleep) can come in to help.
It's one of these force multiplier-type things because I think most people know now that sleep and stress management are foundational aspects of living the best version of yourself. Having something like psychobiotics and these formulas to help you in that is going to have dramatic impacts on your life. It certainly has in my life. -Kriben Govender
It creates resilience, which is really important because like we said we're going to always be exposed to stress and stressors and things like that. Life is stressful but your body has to be able to deal with it. Where we're failing right now is that we're not allowing the normal systems to deal with it appropriately because our microbiomes are messed up.
Leaky Gut, Leaky Brain, and Leaky Skin
I've always been focused on the body's barrier systems. Barriers play a crucial and dynamic role in how various systems function, acting as both protectors and regulators. For many years, my primary focus has been the gut, a unique and highly dynamic barrier.
There's this condition called leaky gut, where the barrier system of the gut becomes compromised as a result of changes in the microbial ecosystem. As the integrity of the gut lining breaks down, the mechanisms that maintain its function start to fail. This leads to chronic low-grade inflammation, which has been identified as a major risk factor for chronic disease. In the 2015 meta-analysis, it was shown that leaky gut is one of the most significant drivers of chronic disease and mortality worldwide.
My interest in barrier systems naturally led me to the brain. The blood-brain barrier is another critical protective layer, and research has revealed a strong connection between leaky gut and leaky brain. When the gut is compromised and inflammation becomes chronic, the brain barrier also weakens. This allows more toxins and harmful compounds to enter the brain, disrupting cognitive function and overall neurological health.
Rate of Skin Ageing As a Predictor For Chronic Disease
Another key barrier that most people are familiar with is the skin. Your skin serves as a crucial protective shield between your body and the outside world. Unlike the gut, which is highly dynamic (constantly allowing in nutrients while blocking harmful substances) the skin is primarily designed as a physical barrier. The skin has multiple layers, making it much thicker than the gut lining, which consists of just a single layer of cells. It also contains a lipid or fatty acid layer that helps reinforce its protective function, along with structural components like collagen and elastin that provide strength and flexibility.
It turns out that the barrier function of your skin can be compromised, leading to a condition known as "leaky skin." The significance of this was underscored by a fascinating series of studies called the Baltimore Longitudinal Study of Aging. This study was groundbreaking because it was the first to track individuals over 50 years, using each person as their own control. Researchers followed participants from their late 20s into their 80s, examining how their bodies aged based on factors like lifestyle choices, environmental exposures, and more to understand what was happening to the body during the aging process.
With most aging-related studies, the way they're done is they take a current older group. Let's say they take a bunch of 80-year-olds and then they compare them to a bunch of 30-year-olds. They look at many different functions to understand the difference. The problem with that kind of approach is these 80-year-olds went through very different things at 30 than the current 30-year-olds go through. It's not a good apples-to-apples comparison. These researchers negated that by saying, you know what, we're going to follow thousands of individuals.
Most aging-related studies are conducted by comparing a current older group, like a set of 80-year-olds, to a younger group, like 30-year-olds. Researchers examine various biological functions to highlight the differences between the two groups. The problem with this approach is that the 80-year-olds lived through very different circumstances at age 30 compared to today’s 30-year-olds. This makes it an unreliable comparison. These researchers negated that by saying, “We're going to follow thousands of individuals over their lifetime.”
When they were looking at what were some of the predictive features of aging that could predict chronic disease development and mortality, the best predictor they found was the condition of your skin. They called this “age skin” and the characteristics of it are:
-Fine lines
-Wrinkles
-Dryness
-Hyperpigmentation or discoloration of the pigment throughout the skin
-Redness
-Thinning of the skin
All of these things that none of us want cosmetically but they are also independent risk factors for chronic disease. Initially, it was assumed that skin problems were simply a reflection of an unhealthy internal state. The idea was that these individuals had internal dysfunction, which then manifested as skin issues, eventually leading to chronic conditions. However, that’s not the case. Skin dysfunction often appears before the corresponding pathology is detectable in the body. So what’s happening here? The skin dysfunction stems from changes in the skin microbiome. Just like changes to the gut microbiome or the brain, alterations to the skin microbiome affect the barrier function of the skin.
When the skin microbiome is disrupted, it compromises both the skin’s protective barrier and its overall function. This leads to the development of fine lines and wrinkles, a direct result of dysbiosis on the skin. As the skin becomes leaky, toxins, bacteria, and viruses can penetrate deeper layers where they normally wouldn’t be found. This triggers an immune response, causing inflammation in the affected area. The immune system tries to repair the damage, but in doing so, it worsens the disruption of the skin’s barrier. This process leads to more leakage and, in some cases, these harmful substances can enter the bloodstream, contributing to chronic low-grade inflammation.
For instance, a study showed that aged skin can be used as a predictor for conditions like osteoporosis, Alzheimer’s, and cardiovascular disease - all of which seem completely unrelated to the skin. Researchers found that they could assess aged skin to predict the onset, severity, or risk of these conditions.
Of course, it's no surprise that we're creating dysbiosis on our skin. We put on so many different personal care products with harsh preservatives and antimicrobials. We are constantly sterilizing our skin which causes our skin microbiome to become decimated over time. As a result of this, it's creating a barrier function and leakiness in our skin. Not only does that make our skin appear worse, but it also makes it appear aged, creates inflammation, or triggers things like eczema, psoriasis, and acne. It eventually causes leaky skin and creates a chronic disease risk. So just like how we have to maintain resilience in our gut and seal up the lining, we also have to do that on our skin because it's another independent risk factor.
There's almost this two-way aspect of it. It’s looking after your gut to make sure it's not leaky, to let all these nasties into the bloodstream, and to also look after the skin so that barrier integrity is maintained to stop any nasty bacteria from getting in that way. -Kriben Govender
Cutibacterium Acnes and Acne
So how's that dynamic of C. acnes playing out in the skin? This is a great example of an opportunistic organism that is overgrowing. It is not abnormal to find C. acnes on your skin, most of us have some degree of it. It may start to overgrow because:
-Your skin is too oily
-You are not cleansing enough
-You are driving inflammation from a dysfunctional gut in the bottom layers of the skin
-You are using too many antimicrobials
Then what happens is that C. acnesis can infect the pores in your skin. Then it will cause your sebaceous gland to release more sebum as a way to try to protect the barrier of the skin. Then this sebum enters and swells the pores and on top of that, the C. acnesis is creating an immune response. Then you have redness and swelling which becomes a pimple. Most people who are struggling with acne have an overabundance of C. acnesis.
We started with this approach because changing the skin microbiome produces such a clear and measurable effect. To test this, we focused on individuals with severe acne, particularly those with inflamed, red lesions. First, we performed skin swabs to analyze their C. acnes levels. Then, we applied a quorum-sensing bacteria to their skin (one that could compete with C. acnes and bring its levels down) to see if it would improve their skin condition.
Sure enough, in as little as two to four weeks, the results were dramatic. 90% of participants experienced an 80–90% reduction in inflamed lesions. Before-and-after swabs confirmed that C. acnes, which initially made up 60% of their skin microbiome, had dropped to just 13%. The transformation was remarkable, not just in the clarity and tone of their skin but also in the overall complexion and smoothness.
We’ve seen similar improvements in conditions like rosacea-like redness, eczema, dermatitis, fine lines, wrinkles, and even pore size. The moment you shift the skin microbiome toward a healthier balance, you start seeing visible changes. More importantly, you’re also reinforcing the skin barrier, preventing it from becoming leaky and vulnerable to inflammation.
Siv Biome, Serene Skin, and Gut Skin Axis
There are two different products we have developed for the skin: Siv Biome and SereneSkin. Serene Skin works through the gut-skin axis. When your immune system is dysfunctional (as a result of a dysfunctional gut), it's going to attack things with a much more serious inflammatory response. Imagine that you have a dysfunctional gut and an opportunistic microbe sitting on your skin, like Staph aureus. The Staph aureus microbe creates toxins that trigger the immune system. Since your gut is dysfunctional, the immune system is going to have an overt reaction and damage the skin in that area by this blow-torching response that we talked about earlier. This damages the lipid layer, the fatty acid layer, and the skin cells. This creates dry, patchy lesions in that area.
The same thing happens with acne. When you have a dysfunctional gut microbiome, the presence of Cutibacterium acnes in the pores will trigger a more profound immune response for those individuals to get red and bumpy lesions. That's the immune system reacting to it quite a bit as well. One of the benefits is being able to modulate the immune response from the gut so your immune system is not overreacting.
On top of this, if you can modulate what the skin microbiome looks like, you reduce the number of triggers that are on the skin. The worst-case scenario is you have a dysbiotic skin microbiome and a dysbiotic gut microbiome. This combination causes things like:
-Acne
-Eczema
-Rosacea
-Psoriasis
-Premature aging of the skin
What you want to do is manage the gut microbiome which is what SereneSkin does (in ways that are most important for the skin).
On the other end, Siv Biome is topically used and manages the skin microbiome by providing resilience. A healthy skin microbiome, like a healthy gut microbiome, allows your skin to encounter negative effects like too much UV radiation, irritants, toxins, and other environmental things. They won’t cause damage because it provides resilience in the same way that your gut microbiome can provide resilience to things that you consume that may not be that great for you.
So it's a two-pronged approach, one focusing on the gut, the other one topically applied onto the skin. Perhaps through modern living, we've nuked our skin with all these chemicals and applications of nasties, like chlorine and water. On the other hand, applying this spore-based, most likely soil-type organism, is like going back to old times and putting microbes back that were typically in the skin and environment. -Kriben Govender
When you look at the skin microbiome, what you start to realize is you have permanent residents on the skin that change based on the influence around it, but for the most part, you're encountering transient organisms in the skin. Transient organisms from the environment have a very positive effect on the permanent residents of your skin. These spores act as transient organisms that can modulate your permanent residents and certain features of the skin. It is similar to having a more holistic lifestyle and being exposed to nature and dirt rather than what we get exposed to on a modern level.
It works so simply and beautifully because you use one to two drops a day after you wash your face and put your moisturizer on. You can also mix it into your lotion and use it on your body to protect all of your skin microbiome. This makes a massive difference in the features and characteristics of your skin. If you're someone struggling with things like acne, eczema, or redness of the skin, you'll see a profound difference in a short amount of time.
H.pylori, Cancer, Pyloguard L Reuteri Postbiotic
Over 50% of the adult population has infectious levels of H. Pylori and often we just reinfect each other in the household. H. Pylori is a big issue because not only does it cause things like gastroesophageal reflux, ulcers, and gastritis - it can also cause autoimmune conditions and then cancer. It is classified as a class one carcinogen by the World Health Organization so it is very potent.
The conventional way of trying to go after it is by something called triple therapy, in which they use two broad-spectrum antibiotics and then PPIs, proton pump inhibitors. The proton pump inhibitors are there purely to try to stop some of the reflux-like symptomology, but it's not doing anything to go after H. Pylori. It's making things worse generally.
We discovered a fascinating bacterium which is a Lactobacillus Reuteri, and what makes it remarkable is its sole function - it binds to H. pylori and removes it from the system. The cell membrane of this bacterium has a strong affinity for H. pylori’s membrane, allowing it to surround the pathogen - even deep in the stomach’s mucosa. It grabs onto it and escorts it out of the body through defecation. It doesn’t touch or interfere with anything else and this is the sheer brilliance of microbes. No amount of money, research, or engineering could create a microbe that performs this task as perfectly as nature already has.
But here’s what’s even crazier - it doesn’t even have to be alive. This isn’t a living probiotic. The cell is dead, yet its outer membrane still retains a strong affinity for H. pylori, allowing it to bind, neutralize, and eliminate it from the system. It doesn’t need to colonize or perform any other functions - its job is simply to seek out H. pylori, bind to it, and remove it. It’s one of nature’s most elegant microbial defense systems. It's called co-aggregation, which is a well-documented way in which microbes can compete with each other.
I've thought a lot about why this bacterium might even exist. After all, it’s a naturally occurring microbe, not something we engineered or created. We simply have access to a vast library of bacteria that we can screen for specific functions. What makes this bacterium particularly intriguing is that it performs its function even when it's dead. That’s an important detail to consider. Imagine that some people naturally develop this bacterium in their GI tract. Bacteria emerge and evolve for many different reasons, and microbial ecosystems are constantly shifting in response to their environment.
Now, let’s say an individual had a unique distribution of Lactobacilli in their gut but also experienced an overgrowth of H. pylori. Over time, this Lactobacillus strain could have developed an affinity for binding to H. pylori, simply as a survival mechanism. Since microbes are highly competitive, it’s possible that through natural mutagenesis, this bacterium adapted to recognize and remove H. pylori because it was disrupting the balance of the system. And once it performed its job, it simply exited the body through defecation.
Over time, this bacterium developed the ability to perform its function even without being alive. Once it exits the body through defecation, it’s already dead by the time it reaches the outside environment. But considering that humans historically lived in close-knit communities, where exposure to soil, gut contents, and even trace amounts of fecal matter was common, people in those environments inadvertently consumed this bacterium, even in its dead form, through dirt or contaminated food.
As a result, those who were exposed to this bacterium gained protection against Helicobacter pylori. This gave them a survival advantage, improving their overall health and resilience. Over generations, this natural cycle of re-exposure helped sustain and spread the bacterium within human populations. It’s an incredible example of symbiotic evolution, showcasing how microbes can shape and support human health in ways we’re only beginning to understand. It is so important to take care of H. pylori if you suspect you have it and because PyloGuard is so gentle and the only thing it does is remove H. pylori, you can use it even if you just suspect you have it. It is important then to treat everybody in the household or you'll simply get re-infected.
H. pylori is a widespread issue, affecting so many people and significantly disrupting the gut ecosystem. It can alter gut pH levels, worsen dysbiosis, and create a cascade of gut health problems. That’s why having a tool like PyloGuard is truly a game-changer. If you or someone you know is struggling with H. pylori, I highly encourage PyloGuard. It has the potential to dramatically improve gut health and truly change your life. -Kriben Govender
Kiran's Top Gut and Skin Health Tips
Be conscious of what is happening in your system and what you're putting into it. This consciousness allows for the greatest advances in your health because it allows you to think about your choices on a day-to-day basis. You also have to be mindful of your microbiome.
You have an amazing ecosystem passed down from generation to generation for over 100,000 years from our earliest ancestors who have gone through hell to create this ecosystem and pass it down to future generations. We must try to preserve it and improve it so we can pass it down to future generations as well. Our microbiome accounts for more than 50%-60% of our functionality. If we destroy it, we're destroying our capabilities which leads us to pass down a dysfunctional biome to our future.
This compromises their ability to exist in the world. You can use probiotics, prebiotics, make good dietary choices, start fasting, manage stress, get quality sleep, remove processed foods, and so many other things - but start with being conscious of this ecosystem that you're so lucky to have and then know that you have to preserve it for future generations. Make sure to share this blog post with a friend who could benefit from this information!
