Microbiome with Kiran Krishnan: Rational Wellness Podcast 163

Kiran Kirshnan discusses The Microbiome with Dr. Ben Weitz and the Functional Medicine Discussion Group.

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Podcast Highlights

6:55  Among its other roles, the microbiome is responsible for the maturation and proliferation of immune cells like T cells, B cells, and macrophages, etc... Our bone marrow produces B cells and our thymus produces T cells, which is like producing 15 year olds to defend our country, but in order for them to succeed they must first go through basic training and learn how to fight and get their equipment, which is what the microbiome does. This has been studied in mice without a microbiota and you see very poor and complete attenuation of the development of their immune system. The microbiome also supplies the energetics, like butyrate, and the equipment for the natural killer cells, the macrophages, and the dendritic cells of the immune system that are continuously circulating around looking for pathogenic viruses and bacteria to attack or to use the compliment system to neutralize it. Everything inside our bodies is covered by a mucosa. This mucosal surface of the inside of our bodies are approximately 4,000 square feet, which would be a really large house to live in. It is in this mucosa where the viruses and bacteria interact with our microbiome and this is where all the sampling and action takes place. 70-80% of our immune system is centered around our gut and in such eubiotic mice, this never develops.

12:58  There is a Prevotella-to-Bacterides ratio that is reported on the Biome Fx stool test that Microbiome Labs is working with. When people consume a lot of meat and protein, you tend to start to lose prevotella and then you start to increase bacteroidetes. This imbalance tends to be associated with insulin resistance and the inability to be able to build glycogen storage, both part of prediabetes and metabolic syndrome. Such patients also tend to get lethargic and tired at some point during the day because they are struggling to produce energy.  Some of these people with lower levels of prevotella and higher levels of bacteroides will have blood sugar drops in the middle of the night and they may get awakened by this. Kiran mentioned a study that will be published soon that showed that by adminstering a prebiotic that raised levels of Akkermansia and bifidobacteria along with the spore probiotics, these obese patients exhibited 38% reduction in visceral fat mass along with improvements in blood sugar regulation.

18:47  Kiran is involved in a prediabetes study with UCLA using the prebiotics, the probiotic, and also berberine, which is a type of herbal bitters and could be looked at as a natural metformin.  Bitters like berberine can trigger peptides like YY and GLP-1, which are transducers that improve leptin response and increase fat burn by increasing something called cyclic AMP.  It stimulates all of the cells in your body to start burning fat for fuel, it improves gastric emptying and motility in the gut, and then it dramatically improves the insulin sensitivity as well. And prediabetes often results in diabetes in the next number of years and diabetes dramatically increases the risk of almost all chronic conditions.

23:42  In order to help with weight loss, the best thing to do is to do intermittent fasting.  You can start with 12 hours and build up to 14-15 hours. Intermittent fasting will cause Akkermansia and bifidobacteria levels to increase and the microbiome diversity will increase.  It’s complicated to explain, but this type of intermittent fasting can actually improve the microbiome and stimulate certain types of bacteria to grow and certain other species to become reduced. Also taking the right prebiotic or resistant starches will promote the formation of butyrate, which is important for metabolic health and which turns on the cyclic AMP process that causes all of your cells to burn fat. But taking oral supplements of butyrate does not work because it will get absorbed in the stomach or small intestine before it makes it to the colon. Butyrate enemas can work, because you are putting it into the large bowel, but even better when it is produced endogenously by having the right bacteria and feeding them the right prebiotics.


Kiran Krishnan is a Research Microbiologist and has been involved in the dietary supplement and nutrition market for the past 20 years, including hands on involvement in university research.  Kiran is a Co-Founder and the Chief Scientific Officer at Microbiome Labs, a leader in microbiome and probiotic research. He is a frequent lecturer on the Human Microbiome at Medical and Nutrition Conferences.  He is currently involved in over 18 novel human clinical trials on probiotics and the human microbiome. Kiran is also on the Scientific Advisory Board for 7 other companies in the industry. Kiran has published clinical trials in peer-reviewed, scientific journals and several global patents in his name.  The new stool test he has helped developed is the Biome FX

Dr. Ben Weitz is available for nutrition consultations, including remote consults via video or phone, specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111 or go to www.drweitz.com. Phone or video consulting with Dr. Weitz is available.


Podcast Transcript

Dr. Weitz:            Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talked to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates. And to learn more, check out my website, drweitz.com. Thanks for joining me and let’s jump into the podcast.

                                Hi there, this podcast is a recording of our monthly Functional Medicine discussion group meeting, and it’s similar to the normal podcasts, and that it’s basically an interview style, in this case it’s with Kiran Krishnan of Microbiome Labs who sponsored this podcast. And the topic was the microbiome, and we were having an amazing discussion and it went on for about 90 minutes.  Unfortunately, I didn’t hit the record until about 30 minutes in, so I’m going to try to set this up for you so that it’ll make some sense. So I’m going to give some a little introductory remarks to set up the topic, and then just keep in mind that it’ll start with the speaker speaking and I’ll try to help with what he was talking about. So let me set this up. So as I just mentioned, the topic for today is the microbiome, which as many of us know is of crucial importance for our overall health and it’s no accident that many of us in the Functional Medicine world tend to start by looking at the gut as the most important underlying factor or one of the most important underlying factors in many aspects of our health.  Just to be clear, the more than one trillion bacteria, fungi, protozoa, and viruses that live largely along our digestive track, especially in our colon, but also in our small intestines as Dr. Pimentel explained to us last month, but also on our skin, in the vagina, in our nearly every mucous membrane that the body is referred to as our microbiotaThe microbiome is the genetic material of all these microbes. Now, the bacteria and the microbiome are incredibly important for our health as all of us know and we’re starting to learn about some of the importance of the fungi, and there’s even been some interesting data looking at the benefits of parasites. But we’re going to focus on the bacteria today and these bacteria help us to digest our food, regulate our immune system, protect against other bacteria that cause disease, and produce various vitamins, amino acids, short chain fatty acids like propionate and butyrate, and neuro-transmitters among other important substances.

                                The father of Functional Medicine, Dr. Jeffrey Bland once said, “The relationship between our diet and the trillions of bacteria in our intestinal tract is one of the most important features that regulates the way our genes are expressed.”  We now know that the concept of trying to map out the microbiome so that we can determine which ideal set of specific microbes determines a healthy microbiome is no longer a practical definition.  What I mean by that is we thought at one point that if we simply figured out exactly which set of specific bacteria map out a healthy microbiome, then we could just try to duplicate that, and now we know that it’s way more complex than that. There’s a huge amount of diversity in what constitutes a healthy microbiome and that’s between people living in different countries over the course of their life, and many different factors.  So unfortunately that simple definition is not going to work for us. So given that what are some of the factors that can help us determine if a given patient has a healthy microbiome? Or if their microbiome may be contributing to their disease or symptoms or imbalances?  For example, there’s growing body of evidence showing that having a more diverse microbiome is associated with improved health, and then the lack of diversity is associated with obesity, inflammatory bowel disease, obesity, diabetes, and many other conditions.

So Kiran Krishnan is here to enlighten us on some of these topics. And he’s a research microbiologist who’s been involved in a dietary supplement and nutrition market for the past 20 years, including hands on involvement in university research.  Kiran is a co-founder and the chief scientific officer at Microbiome Labs, a leader in microbiome and probiotic research. He’s a frequent lecturer on the human microbiome at Medical and Nutrition Conferences. He’s currently involved in over 18 novel human clinical trials on probiotics in the human microbiome. And he’s on the scientific advisory board for seven other companies and he’s published clinical trials in peer reviewed scientific journals.  So Kiran, we started off the discussion by me asking Kiran about what are some of the most important components to a healthy microbiome. And he talked about one thing that’s important is that there are certain key stone, super important species. He talked about akkermansia muciniphila, he talked about faecalibacterium prausnitzii, and he also talked about some of the ratios like the Firmicutes to Bacteroidetes and the Prevotella-to-Bacteroides ratio.  And now as the discussion starts, he’s talking about how the microbiome positively affects the immune system and how these microorganisms actually help with the maturity of our immune cells?  So with no further ado, we’re going to go right into discussion with Kiran Krishnan speaking. And I hope you really enjoy this, even though we missed the beginning, there’s some amazing, interesting information that he’s sharing with us.

Kiran:                    Maturation and proliferation come from the microbiome predominantly, right? So we have certain amount of machinery to make immune cells but we’re making baby naive immune cells. And it’s the role of the microbiome to train and mature, and then proliferate those immune cells in order for them to actually do their job. The analogy I give is like, we can make children that are immature and small and tiny, and we can’t send our, 15-year-old without any equipment to war, right?  If we want them to go out and defend the country they have to go through basic training and all the training, get the equipment and all that to actually be able to go and fight. So what our bone marrow and what our thymus is doing is actually producing children essentially, which are ineffective at fighting for us. And then our microbiome trains those soldiers. So without the function of the microbiome, you would not get maturation of those T cells, B cells and macrophages and so on.  And this has been studied extensively in no biotic mice, for example, the germ free mice, right? When you rear a mouse germ-free meaning it has no microbiome, you see very poor and complete attenuation of the development of their immune system. In fact, the amount of immune tissue in the gut, which is where about 70, 80% of your immune tissue exists, that becomes attenuated dramatically. So you don’t even develop all of that immune tissue in the gut.

                                A second part to that first claim is a lot of the energetics that the roving immune system requires in order to continuously circulate through. And then when they find something, attack it, eat it up, use the compliment system to neutralize it or the natural killer cells and their ability to use nitric oxide and all the super oxides, all of that equipment and energetics come from the microbiome.  So the microbiome produces the equipment for our defense cells to kill off viruses, bacteria infected cells and they produce the energy, like butyrate is a really important energy source, macrophages and dendritic cells who are circulating around trying to protect us. So again, that relationship is so intimate and the immune system would cease to exist and function if it wasn’t for the microbiome. Then the claim about the neighborhood watch, I’ve been trying to eliminate the importance of the microbiome for people using what I think are sensible analogy.

                                So think about inside the body, everything is covered by a mucosa. So we used to say that the skin, the outer skin was the largest organ in the body, it’s a huge barrier, it’s protecting us, but the skin is only about two square meters in surface area. The mucosa on the inside is about 400 square meters. So it is way larger in terms of area than the skin. And most people here are from the US, so translation of 400 square meters is it’s close to 4,000 square feet.   So imagine an apartment or a house that’s 4,000 square feet, we’d be pretty happy in that space. All of that is packed in as our mucosa. So a virus or bacteria basically enters through a mucosal layer, whether they’re going into the eyes, nose, mouth, they’re going in through your genital tract or even through the skin, they’re going to enter the mucosa.  So that’s where all the sampling and action takes place. Now, in this mucosa, you’ve got about 40 trillion microbes that already lived there, right? So imagine you’ve got 40 trillion microbes covering the space where new pathogenic microbes enter and it’s a job of the immune system to somehow sift through all of the 40 trillion to find the one or two that might be causing you a problem.  And in fact, to survey those 40 trillion or so microbes that already live in your system, you’ve got about 200 million immune cells that do that job, right? So it’s a 200,000 to one ratio.

Dr. Weitz:            Wow.

Kiran:                    It’s an absolute mind-boggling feat when you think about it. The analogy I give is imagine you’re at a music festival and it’s good to imagine it because it’s never going to happen again, or at least not for another year or more. But imagine where like a really fun music festival and it’s in a pretty big field and there’s 200,000 attendees there. So that’s a lot of people, it’s a big event.  Among that 200,000 attendees, you get word that there may be five that are potentially egregious, that could be toxic and somehow hurt some of the other attendees could bring all kinds of paraphernalia and drugs and really kind of cause issues. And you are the lone security guard in that sea of 200,000 people and it’s your job to find those four or five potentially harmful attendees, it would be an impossible task.  The only way you could do it is if the other 199,995 attendees are also keeping eye for you being a neighborhood watch and can radio you, should they see anything suspicious? That’s the only way you can serve it, that’s what occurs in your body. The sea of microbes that predominate cells, all of the cells in your body, they are the neighborhood watch for their immune system when they sense a new pathogen entering a system, whether it’s in the lung with the along microbiome or your sinus cavities in your gut, anywhere else in the body, the microbiota, the resident microbiota in that space signals to the immune system that something is going on, here you got to come pay attention, right?  That’s the only way the immune system can survey this amazing surface area that is already covered with potentially harmful microbes.

Dr. Weitz:            Somebody asked the question, I guess you had mentioned a Prevotella-to-Bacteroides ratio, and maybe you could explain what that is and its importance.

Kiran:                    Sure. Yeah. And what’s interesting, another interesting thing we’re seeing prevotella and bacteroides are also two file up. And this is not bacteroidetes which is the one we were talking about with firmicutes, this is bacteroides, so it’s very close in name but slightly different. What we’re seeing is that when people consume lots of meat and protein, you tend to start to lose prevotella and then you start to increase bacteroidetes. And again, not to confuse me, but this is not the bacteroidetes we were talking about earlier, this is bacteroides.  And what we start to see in this pattern is the formation of insulin resistance. There’s two things that occur, one is the inability to balance blood sugar levels, and then the second thing is the inability to build glycogen storage. So people that tend to have really low prevotella and much higher bacteroidetes tend to have blood sugar dysfunction, and then also tend to have, like get really lethargic and tired at some points of the day they can’t produce the energy.  This is really profound because they’re seeing this more and more in the Western world. And when we do the biome effects test, this is another one of those functionalities that we measure. What’s interesting about when I’ve done a consult, so one of the things that we offer for all of you guys that you should know when you start getting the test done for either yourself or your patients, we offer consults with either our biome effects clinical director, Dr. Sam Molt or we’ve got groups within our learning and development team that will go over the test with you so you get familiar with it, right?   But for some practitioners who are friends of mine, I’ve done it myself and they’ll send me their patients test beforehand and I’ll tell them, “Don’t tell me anything about the patient,” in the first few minutes I’m talking to you, I want to guess what they’re coming in to see you about, just from looking at their tests. And so far, I think it’s been five out of five that I’ve been able to guess.  And the last three have been this same issue like, are they having glucose metabolism issues? Which they may not know because they’re not necessarily pricking their finger and testing the glucose levels because they’re not diabetic. But the way it cycles is it causes massive drops in blood sugar levels in the middle of the night. Some of these people awakened because of that, they get a panic response, during the day, they have real big swings in energy levels.  And then when you encourage them to do a 24-hour glucose and insulin cycle, you see these massive swings up and down throughout the day, and they’re not diabetic, their A1C is may be a little bit of elevated but they’re not completely diabetic. And all of them have this diminished prevotella and really high bacteroides.

                                So that’s another function that dictates like, and it doesn’t have to be obese, like the last two people I talked to about this one was 110 pounds, so she’s not in any way shape or form obese and never has been. But because of multiple rounds of antibiotics and because she has SIBO like condition, she’s basically completely eliminated plant-based foods and she’s very high on the protein and that starts to cause that dysfunction.  So that’s another one that we tend to look at what people in metabolic dysfunction is, how do we bring back that ratio, get that akkermansia up. Between those two things, you’ll start to see a big change, we have a study publishing just on that recently, I’m sorry to keep running on about this, but we have a study publishing recently where we took obese individuals, so these are people, the BMI of 30, 30 to 31 somewhere around there.  So they’re not morbidly obese but they’re overweight. And we did full DEXA scans, we were looking at visceral fat, subcutaneous fat, we were looking at a whole bunch of metabolic parameters. There was a 90-day study, right? And what we did is all we added into their system, and this was a placebo controlled study was a little bit of a prebiotic that we know increases Akkermansia and bifidobacteria as well and then the spores, the spores that stopped the LPS, the leaky gut.  It was a 90-day study, we told them not to change anything about their diet, don’t add any exercise in that they weren’t normally doing. So they’re continuing all of the behaviors they normally continued that kept them overweight and kept them gaining weight.  And what we saw in that 90-day period with no changes in diet, exercise or anything was in the group that was getting that probiotic, prebiotic combination. We saw a 38% reduction in visceral fat mass, and that’s a really dangerous fat around the organs. We saw some weight reduction as well but weight is just not a great measure of metabolic activity, but doing the DEXA scan we saw real fat being lost quite dramatically. And we also saw an inching up of their lean mass, so they were putting on some lean body mass, and then we saw all of these beneficial metabolic changes as well.  So that just goes to show without even diet and exercise and those other aspects of it, just shifting the microbiome we can start shifting their metabolic profile. And then if you add diet exercise and all that to it, the results can be quite profound.

Dr. Weitz:            That’s amazing. Can this be used as an adjunct to working with a patient with diabetes or prediabetes?

Kiran:                  Absolutely, yeah. In fact, we’re starting a diabetes, a prediabetes study with UCLA right now on the same principles but in this case, we’re going to have the probiotic, we’re going to have components of the prebiotic but we’re also adding in bitters, in fact berberine. And one of the important…

Dr. Weitz:            Natural Metformin.

Kiran:                  Exactly, completely natural Metformin. And one of the things that’s really interesting about it and the professors that we’re working with already have published on some of the mechanism of action of bitters, we have bitter receptors right in the upper part of our GI, right where the stomach dumps out, and then in the lower part of our intestines as well, those bitters trigger things called peptide YY GLP-1, these are transducers or transmitters that actually improve leptin response, increase fat burn by increasing something called cyclic AMP.  So it stimulates all of the cells in your body to start burning fat for fuel, it improves gastric emptying and motility in the gut, and then it dramatically improves the insulin sensitivity as well. So simple thing like that and we know that, you guys all know that prediabetes is going to be one of the biggest health pandemics in the next couple of decades because not only do we have so many diabetics right now in the world, we have four times as many prediabetics as we do diabetics and almost 80% of them are going to become diabetics over the next 10 years.   And when they all become diabetics, morbidity and mortality for all of the chronic conditions increased dramatically with diabetes, including COVID right? The mortality rate for diabetes with COVID is seven-fold, seven times higher than a non-diabetic. And that’s scary because in the US we have lots of adults and even some children who are diabetic.

Dr. Weitz:            Absolutely, get into discussion with somebody about COVID, they go, “Well, it’s only people who have these high risk factors.” And when you look at the American population you’re talking about obesity, we’ve got 70% of people are overweight read in the number of people with diabetes and heart disease and autoimmune or immunological compromise. And then you add some cardiovascular conditions, you’re talking about a huge percentage of our unhealthy population.

Kiran:                  Per CDC data, 60% of US adults have at least one of those chronic illnesses falls under the high risk category, right? Hypertension, diabetes, cardiovascular disease, obesity, 60% or more. So yeah, we have a tremendously high risk population in general which goes beyond just the age factor.

Dr. Weitz:            Right. This should be one of the messages we get out of this pandemic crisis we’re in is we have a really unhealthy society and we’ve got to get do something about improving our overall health.

Kiran:                    Yeah, absolutely. That to me was, I’ve done lots of interviews so far on COVID and the pathology and so on. One of the first interview I ever did, I said, my point was that there is a silver lining here because when you look at this virus it’s developed the capability of taking advantage of our vulnerabilities. And that vulnerabilities, the ACE2 receptor, the ACE2 receptors is expressed in cases of chronic low-grade inflammation, which is a epidemic in our society.  And this pathogen has figured out a way to take advantage of that vulnerability. What it tells us is that we should have resilience against these kind of things, and many people do but it’s really painting a picture of how vulnerable we are as a population. Because the thing is, we’ll get through this one and it’s not as bad as it could be as other viruses could be. It doesn’t have the mortality rate as MERS did or the first SARS did, or Ebola does, it doesn’t have 15, 16% mortality rate.  But somewhere around the corner, that’s another one of these coming around and it could be as infectious but 10 times the mortality rate. Again, taking advantage of our vulnerabilities, so to me that is really the silver lining in all of this is like, we should realize that as a population, we are ill equipped to handle something like this only because our systems are vulnerable. Our immune system can take care of this kind of virus very easily if we are allowing it to function in the right way.

Dr. Weitz:            So, bottom line for patients who are overweight, a couple of people asked questions about this, what can we do now to help in terms of the microbiome to make it easier to lose weight?

Kiran:                    Yeah, so really important practical things and this is exactly what I do too and I’ll go through swings with my own weight, and I actually just saw my sister the other day and she’s like, “How did you lose?” I leaned down over the last two and a half weeks because I was like, “Yeah, I’m getting a little too pandemic chubby. So I got to lean down.” So what do I focus on when I do that? And what I think will be really effective to start stoking people’s metabolism. Number one is the fasting, right? If you can add in some intermittent fasting and yes, it will be hard for certain people to go 14, 15, 16 hours right off the bat, but you could totally taper them up.  If they can go 12 hours without eating 8:00 PM to 8:00 AM for the first week, have them do that next week, go 8:00 PM to 9:00 AM, start pushing them, right? If they can get to that 14, 15 hour range metabolic changes already start to happen. Akkermansia levels will increase, the microbiome diversity will increase, bifidobacteria levels will start to increase. Those will be profound changes for their microbiome.

Dr. Weitz:            So why will our microbiome flourish when we don’t eat anything?

Kiran:                    Yeah, so that’s a really important question. So part of it is about food utilization. So if you think about it, every meal that you eat takes about depending on your system but it will take eight to 12 hours before you deprecate that part of the meal, right? It takes that long to go through your system. Now, the way the microbiome is organized is there are many community structures that feed off of one another, there are primary digesters of the macronutrients that you take in, and then they produce secondary metabolites.  And then those secondary metabolites metabolized by another group of bacteria that then produce tertiary metabolites. And then another group of bacteria can eat those and produce another set of metabolites. So that’s part of the reason it takes so long, especially when the food gets to the colon for it to start passing through and all of the digestion that occurs in the colon to happen, or at least a fermentation to happen.  And the thing is when you have primary digesters, let’s say bacteria A is a primary digester of the carbohydrates that enter in as food products, right? Bacteria A seize the carbohydrates, it becomes really active and it starts digesting those carbohydrates.  When it is active it suppresses the growth and the functionality of vector B, C, and D, right? So it starts metabolizing and then it produces all of these secondary metabolites, its primary food is gone so it becomes, it starts lowering its activity. Then bacteria B jumps on these metabolites and starts producing bacteria B gets to flourish to a certain degree. When its primary food source has gone it pushes goes down the row, bacteria C starts to flourish.

                                So when you give your body time to digest the food and ferment the food completely, you actually get to flourish lots of groups of bacteria. What tends to happen is that bacteria A is digesting its primary food, and then that food is gone then it kind of takes a metabolic risk, bacteria B starts to digest the metabolites. All of a sudden the primary food comes back in, then bacteria A start getting active again, which suppresses this next group of bacteria.   So it’s this staircase type of metabolic process, hopefully that’s… I know it’s a little abstract to think about but hopefully that is understandable. So when you give your gut time to actually process all of the food, you get complete fermentation and digestion, and that completeness in fermentation and digestion allows more and more microbes to flourish that utilize different parts of the meal and diet. So that’s a really important thing to understand.  So if we just continuously keep feeding, we’re really only supporting certain categories of bacteria, others get suppressed, they don’t ever have a chance to flourish.

Dr. Weitz:            Would it be even better to fast for three or five days?

Kiran:                  So there can be some diminishing returns if you go too far, and we need more studies on that. There’s a lot of great studies on intermittent fasting, there’s some pretty good studies on 24, 48 hour fastings, but there’s very few studies so far in longer fast, like six, seven, eight days.  I would think that there’s a point in most people’s microbiome where you start losing the benefit and start gaining some dysfunction from that longer fast. It’s probably less typical for us as a species to go that long without eating than it is to go 14, 15, 16 hours. Our ancestors routinely went that long without eating because they didn’t always have food at the ready, they would wait for the hunger pangs to kick in, to motivate them to go out and start looking for food.  So I would say you push that, the longest I’ve ever done is about 30 hours. And I could tell for me, and I intermittent fast every day, pretty much and have been for the last three, four years. That 30-hour period was kind of, I could feel was not really producing much more benefit for me. So then I had small food, small meals, I started feeling great.

                                So that intermittent fasting becomes really important, that’s one of the easiest things to implement. If you could start getting some prebiotics into them, the illegal saccharides particular, the ones that we use is in that Mega Pre, the fructooligosaccharides that come from Kiwi especially are really important for increasing akkermansia and increasing bifidobacteria. Bifidobacteria is another group of bacteria that are inversely correlated with metabolic dysfunction.   Now, the question is, if I take high doses of bifidobacteria, will I achieve the same thing? In fact, you don’t, you don’t see studies that show high dose of bifidobacteria having metabolic impact. There is one bifidobacteria strain called Blp1 I think that when it’s dead will actually help induce some metabolic improvements. That’s again, one of those special cases where there’s something within that bacteria strain that when it’s killed and it opens up will actually provide a metabolic benefit.  So the prebiotic will do a lot more to increasing your endogenous bifidobacteria, giving that metabolic support. Using the spores can be very powerful to megaspores because it stops that leaky gut. So you want to stop the leaky gut, you want to use a prebiotic to increase akkermansia and bifidobacteria, you want to add in a degree of fasting, and then if you can get them to take additional things like resistant starches, that’ll help because one of the really important metabolites in the microbiome that controls body weight controls metabolism are short chain fatty acids.  Like butyrate is so important for metabolic health, butyrate is one of the main signals that turns on the cyclic AMP process that causes all of your cells in your body to burn fat. Butyrate also helps with the leptin response and the satiety signaling, so they’re really, really important. If you can just increase short chain fatty acids, you’ll start to see changes in weight.

Dr. Weitz:            Is it beneficial to take supplements in butyrate and short chain fatty acids?

Kiran:                   Yeah, that’s an interesting component of butyrate therapy because what they found is that butyrate is really useful in things like colorectal cancer or really severe colitis when you have inflammation in the large bowel, but when you take it orally, it doesn’t seem to help. So what they’ve started doing in hospitals is they all still do butyrate enemas instead to get it into the large bowel, so it actually has that function. So there’s a big question of whether or not orally supplemented butyrate actually will get to the large bowel where it needs to be, or does it get dissipated and absorbed in the small intestine, or maybe even the stomach.  So that’s the part that’s unsure, increasing your endogenous butyrate is not hard at all. Our study that we published last year showed that when we added the prebiotic and the probiotic in, we increase butyrate production by 150%.

Dr. Weitz:            One of the tricky things about using prebiotics since a lot of us have patients with SIBO and they’re very sensitive to prebiotics and fiber, and it tends to flare them up.

Kiran:                    Yeah. That is problematic. So we say with the prebiotic that we use, which are highly specialized oligosaccharides designed to make it to the large bowel so they should not have a lot of bacteria in the small bowel that can ferment it to create the gas and distension, but we tell them to test it. They can go as little as like an eighth of a scoop, mix it into a jug of water, shake it up and kind of sip it throughout the day.  We’ve even had some people that go as far as not being able to take it in orally, so then they do prebiotic enema to get some oligosaccharides into the large intestine, which is where the bifidobacteria acclimates are all there, so you can do a retention enema with the prebiotic mix. So that’s one way to start getting it in there. If you can, because if we can’t do it this way, you might try the other way.

Dr. Weitz:            So it’s interesting as some of these probiotics that are dead are actually more beneficial, myself and I’m sure a lot of the practitioners who are listening probably have probiotics in our refrigerators at our office, which we’ve made a big deal out of making sure that they will refrigerated the whole time thinking that we’re providing an extra benefit, because if the temperature gets too high the bacteria will die and these are more potent. Are we really helping our patients?

Kiran:                    Yeah. No, all of that work to try to keep it alive in the room is really all for nothing because the moment they hit 98.6 degrees in the body and pH a one and a half or something going through the stomach, they just obliterated. And we’ve tested that, we’ve tested 40 or so of the top retail probiotics and even the probiotics in the health space and all of them die going through the gastric system.  So the key is then finding ones that have shown studies that the dead versions are actually beneficial. And that’s specialized. Like for example, with rhamnosus GG, when you kill it and you administer it, it has all of these benefits but regular rhamnosus, the generic version of rhamnosus wouldn’t have that same effect.  You kill it, it’s just dead and it’s not really doing anything, you’re going to poop it out 12 hours later. So the metabolic response modifiers, the types of strains that when dead can have specific metabolic effect are very specialized to those subspecies of the strain, it doesn’t translate to the wild type version of this strain.

Dr. Weitz:            With respect to intermittent fasting, somebody asked the question, do you think it’s more beneficial to skip breakfast or to skip dinner?

Kiran:                  Ah, great question.

Dr. Weitz:            What do you think it matters?

Kiran:                  So yes, there are at least two studies that came out that showed that if your fasting window is basically from the afternoon till the morning that, that actually has a bigger impact on weight loss than the overnight to the afternoon fast. So if you’re fast with somewhere around like 12:00 or 1:00 PM all the way until like 8:00 or 9:00 AM, that seems to have a more profound effect on weight loss and fat loss than the overnight to noon fast.  Now that being said, the overnight to noon fast also has benefit, right? The problem I have, and I can’t do the other way around just because dinner becomes such a big important social thing. Whether it’s business related, it’s family, it’s friends, so it becomes really hard to skip dinner, just from the social side of it.  And so that’s why for me, I’ve not been able to do that kind of routine, I can do the skip the breakfast very easily. Now, the other advantage for me in skipping breakfast is that I can do my workouts in the morning and doing your workout in a fasted state really amplifies your growth hormone levels, and that has a huge metabolic impact as well. If you can fast through the late afternoon and evening and then throw in a workout sometimes somewhere in that evening period, that’s fantastic but a lot of people find it very hard to skip dinner. There are too many social things surrounding dinner.

Dr. Weitz:            Yeah, actually for me it’s easier because a lot of times I’m busy with patients and I don’t really have time. And a lot of patients want to come in after work, and so rather than eat late, a lot of times I’ll just skip dinner just because it’s easier.

Kiran:                    Yeah, that actually has a bigger impact metabolically than skipping breakfast. But if you can’t skip dinner, then skipping breakfast will help as well.

Dr. Weitz:            Is there ever going to be a probiotic, protozoa or fungus?

Kiran:                    Oh, fungus yes, so we already have saccharomyces.

Dr. Weitz:            Yeah. That’s true. That’s true.

Kiran:                    Well established. We will have, yeah, I believe we will, we’ll have potentially things like amoebas, we’ll potentially have protozoas, we may have organisms that we don’t even know exist yet. When prions became a thing with mad cow disease 20 years ago I was actually still in university and it was so interesting to see my immunology, microbiology professors like losing their minds as to what the hell is this weird alien thing.  Because imagine viruses are really fascinating all themselves, because they’re not even living creatures, viruses are technically not alive because they cannot create any sort of metabolic effect on their own, they can’t reproduce on their own, they’re just like a fatty envelope with RNA or DNA sitting in it or protein envelope with RNA and DNA sitting in it and just floating around.  And it just has this mechanism that allows it to bind to certain things, inject its RNA or DNA and hijack the cell. So that in itself is fascinating, then you think about a prion which doesn’t even have that sophistication, it’s just a strand of protein. And this strand of protein, it just so happens the prions that we know of right now are really devastating that’s what created the mad cow disease. So it creates the encephalitis, so basically bus holes in your brain, but it’s this tiny little thing of protein and there’s like no functional way of killing it, that anyone knows it can withstand all kinds of heat, it can withstand all kinds of acid, it’s really mind boggling.

                                So we may find organisms that we don’t even know exists right now that are really important therapeutics within our system. I think the next one’s beyond bacteria and fungus are likely going to be in the parasite family, the parasitic family, just because there’s so much work being done with that already in a fringe world, the helmet therapy and all is considered by many to be like really weird. But the data’s good and they’re showing real progress in certain parts of the world in treating allergies.  And when something like allergies becomes more and more of an epidemic in our country, we’ll start having to go towards those types of therapies.

Dr. Weitz:            Don’t we know that societies where worms are endemic have much lower rates of allergies and asthma and autoimmune diseases?

Kiran:                    Yep, absolutely. And there’s a double edged sword that there are certainly some worms that will then create all kinds of other problems down the road, but absolutely. And I think in part, what that speaks to, to me is it speaks to our disconnect from the natural world. So we’ve evolved to have a pretty intimate relationship with all of these organisms in the natural world.  And the more we disconnect from them, then the more susceptible we become because we’re missing key links to our function and our phylogenetic tree. And so understanding what those things that we’re missing are, and putting it back into our system, I think will be a really big part of microbiome therapeutics moving forward. We are engaged with lots of very big companies in the world and massive companies. What’s exciting about it and then many people are turned off by massive companies. I totally understand that, but massive companies like Nestle, for example, who’ve spent their whole lives feeding sugar to people and sugar to kids.  When you look at their new focus, they’re saying we’re going to de-invest from all of our candy sugar stuff and focus on health wellness and microbiome science. There are companies like Chris Hanson and ADM, Archer Daniels Midland, these are massive billion dollar companies and they’re all seeing the writing on the wall.  I get calls from these kinds of companies and I talk to the leadership within those companies, they’re all trying to figure out how do we focus and hone in on the microbiome. They all see the microbiome as like the big thing over the next several decades to really improve health and humanity. So it’s really exciting. I think we’ll see lots and lots of innovations.  One of the areas that we’ll start to see more and I’m always advising companies to disrespect is the microbiome modulation. We’re getting to understand more that A, if you have high risk for certain types of cancers, you have certain type of microbiome, there are certain features within your microbiome that are characteristic of that condition.  So as we can better monitor and understand and test for those features, we can hopefully modulate features as we go along to fix people’s ecosystems in a very precise way to improve their overall outcomes.

Dr. Weitz:            How does the microbiome change with diet? You mentioned that if we eat heavy meat diet, that that’ll influence the diet one way. And right now in the diet world, we have these really extremes, we have people eating meat only the carnivore diet, we have people only eating vegetables and everything in between.

Kiran:                    Yeah, absolutely, and that to me is one of the scary things in the whole world of wellness and functional medicine is the adaptation of real extreme and exclusive diets. We’re just not designed to function that way. I think one of the things that makes the human species really unique in the animal kingdom is our incorporation of a really large diversity of microbes into our system, which really gives us strong omnivore qualities.  And that omnivore quality actually is a big part of our evolutionary ascent up the ladder, because if you think about other species that we essentially we would be competing with that are obligate carnivores or obligate herbivores, they are very susceptible to environmental and other changes. If you think of a lion is as powerful and ferocious as a lion is, if there’s a drought and the wildebeest levels are low, or its main prey, the lion’s going to starve to death.  If a human is in that same drought, we can go and dig for roots and tubers, we can eat insects, we can eat plants, we can eat rodents, we can eat a whole bunch of different things and survive through that. The same with on the opposite end with the lions prey, the wildebeest was an obligate herbivore can only eat plants. And so if those plants are dead and the Savannah is dry, they’re going to die, they can’t just go and eat insects and they can’t just go and catch a muskrat and eat it.  So we’ve got this really unique capability of producing tools using these hands, we’re upright, we’re [bi-pi-to 00:44:50], we can move long distances and we can eat lots of different things. Our microbiomes are really designed to do that. So the moment we go to a very exclusive diet especially if we do it for long period of time, it’s going to have a long-term negative consequences. I think short-term, like if you’re really trying to change your metabolism and you’re going to go keto for a short period of time, that could be totally fine.

                                Because one of the big benefits of keto is you’re actually eliminating sugar, and that to me is where you get a lot of the benefits of keto. So you can go keto for a short period of time, but then get those vegetables and the plant-based foods back into your diet. You also shouldn’t be going vegan forever and not getting any complexity in your amino acid profile and so on.  So to me, it’s really about much more of a balanced diet and I think that’s how we’re evolved to exist.

Dr. Weitz:            It’s a really big current trend in the Functional Medicine world as you mentioned to talk about the dangers of eating lectins, the dangers of eating meat, because everybody’s going to get heart diseases. And it seems like everybody’s looking to the specialized diet that subtract certain types of foods as the answer to fixing people with certain types of problems.

Kiran:                    Totally, yeah, and that’s a problem because we’re not talking about enough is how do you build a resilient microbiome that handles all of these things? I mean, you talk about lectins, one of the types of diets have tend to a lot of lectins is the Mediterranean diet, they eat lots tomatoes and all that. It’s one of the healthiest diets ever, there’s more studies on the Mediterranean diet than any other kind of diet and we’re talking huge studies and we’re talking 50,000 patients longevity studies on it.  So clearly it has benefit and there’s a way of eating it and there’s a way of preparing it, and the people’s microbiomes are resilient to handle it. We have amazing capability of neutralizing things that are not actually good for us, the anti-nutrients people talk about. If we have a resilient diverse microbiome, we can absolutely neutralize those, we can neutralize glyphosate in our gut, not to say that we should have glyphosate in our food, but just to show the ability the resilience of our microbiome to protect us.  So to me and people always ask me, like what is your focus and goal with your microbiome? What do you try to do? And to me, my goal for health is about being resilient, because I don’t want to have to live a really structured control life in order to feel good. Like you talked a lot of people and you go, “How you feeling? How’s your gut doing?” “Oh, I feel great as long as I don’t eat this, this, this,” and they’d rattle off 17 things. “And I feel great as long as I don’t do this.”

Dr. Weitz:            That’s one of the biggest issues of a lot of us in the functional medicine world, we have these patients that come to see us for these severe gut problems. And gluten was a problem, they cut out gluten, they cut out dairy, they cut out this vegetable, we cut out that vegetable, we cut out, they went on a low FODMAP diet, so they cut out all the cruciferous vegetables and then they found out about the next category of foods to cut out and they come in and they’re eating two or three fruits and [crosstalk 00:48:19] anything.

Kiran:                    Yeah, absolutely.

Dr. Weitz:            And your gut has no tolerance to be able to eat these different types of fruits.

Kiran:                    And the thing is the elimination doesn’t do the healing, and that’s the important part that people need to understand. And in fact, speaking of gluten, there’s a really good study on this, and I think it’s fine for people to avoid gluten if they want to reduce the risk for that permeability. But you cannot avoid carbohydrates, you cannot avoid fiber because one of the big studies on gluten they showed that in the first year of gluten intolerant people going on a gluten free diet, their mortality rate almost doubles.

                                And you would think like, wait a minute, that makes no sense. So these are gluten intolerant people, meaning when they eat gluten, they get all this inflammation, they get all this intestinal permeability. Why is it when they go on a gluten free diet, does their mortality rate increase in that first year? And then it tapers off a little bit in second year, but in that first 24 months, their mortality rate almost doubles.

                                So the reason for that is in Western society and in our culture and our society, more than 85% of our fiber intake comes from wheat. So you’re getting all of this fiber, despite getting the gluten that’s also harming you, but you are getting the fiber component. So then also then you eliminate gluten and most people who eliminate gluten we’ll replace it with proteins and fats.

                                So you’re taking out fiber completely out of your diet and then you’re replacing it with fats and proteins. So now the expectation is what I removed the offending thing my gut should be healing. As it turns out, when they look at these individuals, the gut doesn’t heal at all, it stays susceptible and because you increase the intake of other things like fats that can increase endotoxemia, you are actually increasing your risk for other conditions.

                                So what you should do in that case is eliminate the gluten, that’s fine, but you have to replace it with other non-gluten sources of fiber and so on, because that is what drives the repair. Just eliminate, eliminate, eliminate is not going to cause a repair. We need to maybe temporarily eliminate foods that are clearly offending your system, but then make sure we’re getting things in there to provide some diversity, provide some resistant starches, some fiber, all of those things are really important.

Dr. Weitz:            Is there any way that people following a carnivore diet by eating the entire animal, every part of it. Is there any way they can have a healthy microbiome?

Kiran:                    So if they’re eating the entire animal then potentially, and that would include intestinal content. And we see that in hunter-gatherer tribes, right? So in the hands of tribe in Tanzania and the tribes in Papua New Guinea, when the hunters go out and they catch their prey like in, I think it’s in the one in Tanzania, the porcupine is like a delicacy for them.  And they’re not doing this often, even though they’re called hunter-gatherers, they hunt way less than they gather, they gather a lot more. But they do go out as hunting parties. One of the first things they do when they capture the animal, is they cut open the intestines and then they eat the intestinal content. Most of these animals that they eat are ruminant to certain degree, they’re picking up seeds and nuts and all that from all over the place.  They’re fermenting it in their guts and if you eat that intestinal content, you’re getting all kinds of amazing carbohydrates and resistant starches and so on. So you likely can, if you’re eating connective tissue and you’re getting different forms of collagen, you’re getting some of the glycoproteins from connective tissue, if you’re eating organ meat, if you’re eating brain, if you’re eating liver, you can get diverse enough macronutrient to maintain diversity within the diet.

                                But the unfortunate thing is in the US, when you’re saying, when someone’s saying the carnival diet, they’re just eating a steak and that’s about it. And I’ve met a lot of people like that. I mean, I get to speak at places like the paleo effects like I spoke last year. I met so many people at that show they go, “Yeah, I’ve gone full carnivore.” I’m like, “Okay, what do you eat?” “I eat two steaks a day. That’s it. And sometimes I’ll have a dollop of butter on the steak.”   And I’m like, “Okay, well, that’s not a good thing necessarily.” And also it depends on your microbiome in large part, because if you look at it, one of the ill effects of meat metabolism is the formation of TMAO. And there are certain types of bacteria that produce high levels of TMAO.  If you happen to be one of those people that have high TMAO producing bacteria, and you eat lots and lots of meat, it’s going to cause heart disease. There’s no if, and’s or but’s about it, the studies on TMAO are pretty clear. But if you happen to have very low levels of those bacteria, you can sustain this for a period of time until those bacteria grow because you’re giving it so much meat. So that’s another kind of catch that whole thing is what happens to the food when it enters your system.

Dr. Weitz:            I know this is kind of going off our topic, but I love to get your take on this TMAO thing, because those of us who are working with patients with cardiovascular risk factors we have found that certain supplements, like L-carnitine, incredibly helpful for mitochondria, for the strengthening the heart, and all need super important nutrients for liver health, for brain health.

                                And it’s really hard to, it doesn’t really seem to make sense, it doesn’t fit with our experience that patients who are eating foods or taking supplements with choline or L-carnitine are really putting themselves at increased risk of heart disease.

Kiran:                    Yeah, because of the potential of TMAO.

Dr. Weitz:            TMAO.

Kiran:                    [crosstalk 00:54:28] of TMAO.

Dr. Weitz:            Yeah. So I think the answer to the TMAO question is more about making sure we have a healthy microbiome than about not consuming L-carnitine or choline.

Kiran:                    Exactly. Yeah, because again, it comes back to that balance issue. So one of the things that we test in the biome effects tests is TMAO producing bacteria.

Dr. Weitz:            By the way, if everybody’s not familiar with this, why don’t you explain that Microbiome Labs is offering a stool test. And how can practitioners find out about this?

Kiran:                    Yeah, absolutely. So  the test is called biome FX, like the letter F and the letter X. It’s a whole genome sequencing test, just to give you a little bit about the difference between what we’re doing and what you have already experienced in the market. We started seeing a lot of issues with accuracy in stool testing. One of the big problems is most of the stool tests, in fact, all of the ones you’ve used use something called 16S sequencing, 16S sequencing if you’re not familiar with sequencing information, 16S is like taking random Polaroids of a single of parts of someone’s body, and then trying to piece it together and identify who that person is.   So it’s a really low resolution inaccurate way of identifying species level for the bacteria in your system. So it tends to have a very high error rate. And what the companies aren’t telling you when you look at your test results, and they’re showing certain bacteria that they’ve picked up, they’re not telling you that they have an algorithm in their bioinformatics pipeline that makes a prediction that this is likely the bacteria we found, it’s not absolute at all.

                                In fact, all of the big microbiome research organizations, the American Gut Project, the Human Microbiome Project have come out and said, you cannot use 16S to identify bacteria to the species level. So we saw that as a big problem, and so we wanted to make that in itself a change. So we started working with the top lab in this space called CosmosID on developing a whole genome sequencing test, which means that we actually have to sequence in bacteria’s entire genome from end to end in order to identify, we’re not looking at just little snippets of the bacteria.  So it’s a far more accurate, it’s 99% or more accurate. So you’re getting the most accurate species level information. Now, why is species level information so important? Well, because like we’ve been talking about with the microbiome, it’s really about what does that total ecosystem look like. Outside of the keystone strains you can’t necessarily just pinpoint singular bacteria and their levels as being problematic because everybody at the species level has most of those bacteria different frequencies.

                                And so what we look for is we look for really important trends, well-established trends because in the microbiome, one of the things I say is, it’s not who’s there, it’s who else is there, right? The function of certain bacteria are dictated by what other bacteria are in that environment and what are all of their relative abundances? That’s where the mapping becomes really important. So we can map out functionalities within your microbiome by understanding the species level, relative abundance data, and the best researchers who have done this is led by Rita Colwell.  Rita Colwell is the most decorated scientists in this whole world of microbiome mapping, she’s got 60 honorary degrees including a couple PhDs that she first earned and then 60 other degrees, she’s published 800 papers in this space in peer reviewed journals, which is a mind-boggling amount for any researcher doing work.

Dr. Weitz:            Isn’t it the case that the PCR, quantitative PCR testing is actually more sensitive and specific for picking out organisms? And if you go into a hospital and they suspect CDF, they’re not doing a whole genome sequencing stool tests, they’re doing a PCR test, right?

Kiran:                    They’re doing a PCR test and that’s important because the relative abundance of that pathogen compared to all of the other DNA may be really low. So for them, in order to find that bacterial DNA or viral DNA in the case of COVID or any other virus, they need to amplify that bacteria viruses DNA. And that’s what PCR does, the polymerase chain reaction amplifies the DNA. The problem with doing that in a stool test to try to understand your microbiome is it artificially amplifies the volume of that particular species DNA.  So it gives you erroneous relative abundance numbers, so we need to be able to get really accurate relative abundance numbers. And the thing is that the sequencing work takes longer, that’s another reason why, if you’re ill with something, they’re trying to figure out what is making you ill, they use PCR because it can be done pretty quickly. You can get PCR done in an hour or 35, 40 minutes.

                                The genome mapping using full metagenomics takes much longer than that. However, CosmosID, the lab that we’re working with are the only lab that are FDA approved to do whole genome sequencing for pathogen identification, because now we’re starting to see some issues with PCR, even in pathogen identification because you might go to a doc, or you might have diarrhea and your doctor, your infectious disease doctor gastroenterologists might say, “You might have C diff, this looks like C diff. So let’s take a stool sample and then we’ll look for C diff.” But they were using the PCR, they will amplify the C diff DNA and they’ll pick it up.  Now, C diff may not even be causing you the problem, because C diff may be there but its levels may be low enough that it’s not the one causing you the problem. And the PCR is absolutely focused on that one organism, it’s not like it’s amplifying everything to pick up whatever it can find, it’s going in, honing in on that one organism saying, “Hey, we found some C diff, that must be your problem so we’re going to give you vancomycin all day long.”  Well, that might not be the solution, right? So now the FDA and the infectious disease specialists starting to see that PCR may be problematic even in trying to identify an infectious agent, what may be better is sequencing everything that’s there and seeing what is just popped up at the highest that could cause those symptoms. So CosmosID is the only FDA approved lab in the country that can do that kind of work.  So we partnered with them to get the best sequencing data. And then our other thing that we focus on the stool test is we want to give you functionality, we want you to be able to tell what your patients microbiome tends to do and tends not to do. It’s not absolutes, there’s no absolutes within the microbiome, but you will have a guide for you to understand where the real issues may be within that patient’s microbiome that you can start honing in on to help.

                                And everything we test actually gives you actionable steps that have references. On lifestyle changes, diet changes, and even supplement changes that can help that particular area. Coming back to TMAO, that’s one of the things we test. So you could eat meat and choline there and L-carnitine all the time and be absolutely fine and it’d be very healthy for you as long as you don’t have really overgrown levels of bacteria that create TMAO.  And you may have that because of previous dietary choices, when you bring back balance of the microbiome, then you don’t have that issue. And so one of the things you can do is you could test your patient’s microbiome and say, “Hey, your TMAO levels are really producing bacteria really high, so let’s reduce these kinds of things for a period of time until that comes down, then we can bring them back into the system.”  Just another example of that sulfate reducing bacteria. Nobody would have really thought about it or heard of these things within functional medicine, but they’re so important because one of the things that they do is they take sulfate from sulfate rich foods, and they convert it to hydrogen sulfide in the body which then becomes really inflammatory to the bowels. And so many healthy foods are high in sulfates, seafood is high in sulfates, and the leeks and garlic and artichokes, all of these things, high in sulfate.  So you might have a patient that’s going, “Doc, I’m eating pretty clean. I’m eating healthy fish in a line caught fish, I’m eating these vegetables. I still have really bad diarrhea…”

Dr. Weitz:            I just had a patient today and she had a flatline SIBO breath test which is usually indicative of hydrogen sulfide.

Kiran:                    Yup, exactly. So, yeah, and then you will know from the bio effects test like, “Oh, okay. It’s because your sulfate reducing bacteria are really high, these categories of foods really are actually counterproductive in your gut. So let’s bring those down over time and you could see all of the recommendations that allow to bring that down, bring that down over time and then rebalance microbiome, then you can reintroduce foods like normal.”

Dr. Weitz:            So how do we order this stool tests and how much does it cost?

Kiran:                    Yeah. So the practitioners you can order, I think we sell them in bundles kits of four, there’s no cost to order them of course because you can order the kits and have it within your practice until you have the right patient to use it on. The price that we charge is 299, we leave it up to you if you want to mark it up above that, but that’s a price that we only talk to practitioners about.  So the patients don’t know what the cost of this is. We have a mix of practitioners, some that don’t mark up tests at all but then charge a consultation fee to go through it or some that double the price depending on how they’re set up. So we allow you to decide how to do that. So then the functionality of it is if you have patients coming into your clinic, you can hand them a test, you can either have you or your staff registered the kit for them.   It’s a very quick process maybe it takes two minutes and you can either put in the payment and then charge them back, or you can have them take the kit home and have them register it using your code in there and then they will pay for it directly too. So you can manage it however you want, they do this test at home, we’ve got a very painless sampling procedure. That was another thing that we really wanted to improve, we didn’t want people like scooping poop and doing all kinds of stuff.   So we have this piece of paper that actually sticks to the toilet seat that has a bowl in it and then you take care of your first void and then we give you a brush, a coring brush, and you kind of core through a few spots in the stool, stick the coring brush in the test tube, close it off, then that’s what you mail back the paper, you can actually just unstick it and flush it. So you’re not dealing with actually managing anything.

Dr. Weitz:            That’s cool. It’s always tricky trying to hold that with [crosstalk 01:06:13] basket.

Kiran:                    Exactly, yeah. And the brush, what’s cool about the brush is we even thought about this like, we don’t want you to get too close to the stool. So the brush actually has a long handle when you first get it and you can actually core through the poop sample. I think we recommend somewhere around like five or six times you core through it.

                                And we use a brush because one of the things we found was you’re not getting adequate sampling of the DNA from the stool when you swab the surface or when you scoop a tiny bit of it. The DNA and the bacteria in the stool is not homogenous, so the bacteria on one side is going to look different than the bacteria and the other side and their relative abundances can change. So we wanted you to be able to go through the whole core of the stool and use a brush with lots of bristles to pick up as much as we can.

                                The more you pick up the more accurate the data it would be. So the brush has a long handle, you core through it a few times, you put it into the test tube, and I think you just off the top of the handle and then screw the cap on it, then you’re just mailing it back in a prepaid envelope.

                                And here’s the exciting part about it is we now have an FDA approved COVID diagnostic in the stool tests, and it’s an actual diagnostic meaning you can diagnose COVID in the stool. And that’s really important because studies have shown that you can actually pick up COVID in the stool for up to two to three weeks longer than you can pick it up in the upper respiratory tract. So you might have a patient that was feeling pretty crummy.

                                And in fact, we just had this with one of our employees, she was feeling pretty crummy and she went and got the nasal pharyngeal test and it was negative. But there’s studies that show, you can get up to 50% false negatives with that test. And so she’s like sitting at home having lots of similar COVID like symptoms and doesn’t know if it’s COVID or not.

                            So we’re having to do the stool test instead and the stool test will come back in about four days for the COVID part. The sequencing takes a little bit longer, but the COVID part comes back faster. And if you had somebody that had COVID maybe a couple of weeks ago, I suspect they did, you could still pick it up in the stool test up to two, three weeks after symptoms go away.  So it’s a great way to do that diagnostic, and you can do it at home. You don’t have to go to a testing facility where you’re around a bunch of other people that also think that have COVID and you could kind of keep yourself just safe distance from all of that.

Dr. Weitz:            This has been an awesome discussion Kiran, and I could talk to you for hours.

Kiran:                  Thank you.

Dr. Weitz:            Thank you for being so generous with your time. And so I think we got to most of people’s questions.

Kiran:                  Awesome.

Dr. Weitz:            And I really appreciate it.

Kiran:                  Well, yeah. Thank you so much for the opportunity, I always treasure any opportunity to talk about this with people, because clearly everybody here are the people on the front lines, you guys are the ones making the difference out there. And nothing I do is meaningful until it translates to the work that you do, so I’m always grateful for these opportunities. So thank you, Tanya, so great to see you and thank you for getting this set up for us as well and really enjoyed it, really enjoyed it myself.

Dr. Weitz:            Excellent. And thanks to everybody.

Kiran:                  Yeah. Take care.



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