In this podcast, Gregory Kuehn, President and COO of Prescient Metabiomics, talks about his company’s innovative work in colorectal cancer treatment, as well as their development of a stool test for cancer.
Kuehn earned his MBA from the University of Colorado, and a BS from the College of William and Mary in molecular biology as well as computer science. Kuehn discusses Prescient Metabiomics’ work researching how the microbiome can be used to predict or associate with various diseases.
Kuehn explains their mission at Metabiomics, a pioneer in the development of human microbiome and advanced metagenomic technology. Prescient Metabiomics’ innovative and important research has lead to the development of a non invasive stool test for the early detection of colon polyps and colorectal cancer. Their developments are based on intensive examination of the human gut microbiome. Kuehn provides an overview of their work in inflammatory bowel disease that eventually moved them to research methods to possibly prevent colon cancer.
Kuehn discusses the microbiome in detail, explaining the complex relationships that the microbiome has with the human body overall. He explains biomarkers, discusses toxins, and gives his thoughts on the functional relationship between the gut microbiome and human health in general.
In this podcast:
Gregory Kuehn: Very good. Yes, it’s a joint venture with Prescient Medicine. And that’s where we became Prescient Metabiomics.
Richard Jacobs: And you can say that it was very prescient of you to do so. Right?
Gregory Kuehn: Absolutely.
Richard Jacobs: Well, for listeners that haven’t heard before, tell me about Prescient Metabiomics or Metabiomics. What do you guys do?
Gregory Kuehn: Well, Prescient Metabiomics is a pioneer in the development of human microbiome and metagenomic technology. We have been for the last 15 years developing the technology platform to do advanced interrogation of the gut microbiome and associating the microbiome with health and disease.
Richard Jacobs: Okay. So are there specific conditions that you’re targeting or, I mean like, health and disease, how is that defined according to you guys?
Gregory Kuehn: Well, that’s an interesting point actually. The technology actually represents a new paradigm for looking at human health. We can analyze the microbiome and actually through clinical trials associate the changes in the gut microbial ecosystem with various diseases and conditions. Our company very early on developed a focus on gut health. And so inflammatory bowel disease was an initial focus for the company and that eventually led to the discovery that we can actually predict colorectal adenomas, which presents the opportunity for preventing colon cancer. And that’s largely what our company is focused on now, is developing a screening test for precancerous adenomas and carcinomas with a goal of trying to prevent colon cancer.
Richard Jacobs: Okay. And so what have you seen, how are the microbiomes barely correlated to health or disease? All I hear is that more diverse microbiomes are correlated with better health outcomes. But beyond that, I don’t get any details. What have you guys figured out?
Gregory Kuehn: Well, we’ve as a company dug in a lot deeper. And we’re modeling specifically a situation where there’s colorectal adenomas or colorectal cancers versus healthy and we define healthy with a colonoscopy. And further, we’re digging into the etiology of the disease. So the microbiome doesn’t just help digest food and there’s actually a very complex relationship going on. So the microbiome activates and regulates the immune system. The microbiome is the first line of defense fighting off pathogenic bacteria. And disruption in the microbiome is, it’s kind of what we have developed, we have developed it into a biomarker for these diseases because it’s kind of related to signs of chronic inflammation or perhaps Geno toxins being developed by the microbiome. We’re trying to dig into the functional relationship between the gut microbes and the human host.
Richard Jacobs: So like anything, I have both seen difficile it appears to come out and people that had the antibiotics multiple times, et cetera. But from what I know, it exists in the gut normally just in low levels, but in a dysbiosis situation, now it’s a predominance, so that means like it was always there wasn’t really a pathogen or not until it just reached a stage rich predominance and now it’s causing problems. Like how do you evaluate when, again, a healthy microbiome versus a dysbiosis? Is it by prevalence? Is it by appearance or not the appearance of a certain organism? Is it by other factors?
Gregory Kuehn: That’s a good point. So essentially there’s gut homeostasis that is trying to define gut health and that essentially is a stable configuration of the gut. And there are various ways in which dysbiosis can occur and that’s a dysregulated immune response, a defect in the epithelial barrier or extreme overgrowth of certain pathogenic bacteria or even some bacterial strains that were formally symbiotic that become pathogenic to a certain extent when they’re sort of getting out of whack with the host.
Richard Jacobs: Hmm. Okay. So in particular with the cancers that you’re looking at, what have you seen? Have you looked at the cancer cells themselves and do they interact with the local microbiome differently? Do they attract hyper-specific like microenvironment of microbes that are unique to them? Like, what have you seen there?
Gregory Kuehn: Well, there’s been an absolute explosion in the field and so many researchers all around the world digging into these questions. And so we’ve focused on actually most recently taking a lot of those studies and we’re looking at it from a 30,000-foot view. So, part of this revolution is also AI and machine learning technologies that we’re deploying. So we’re looking at actually hundreds if not thousands of biomarkers and developing approaches to actually tease the signal from the noise. So, exactly there is a question. So what biomarkers are important? What aspects of the functionality of the microbiome are important and how can we actually use that knowledge to incorporate it into our predictive models and diagnostics algorithms ultimately?
Richard Jacobs: Is it a metabolite, the same as a biomarker to you, or are they two different things?
Gregory Kuehn: A biomarker can be anything. It can be a gene, a protein, and metabolite, et cetera. We’re focusing primarily on metagenomics, metatranscriptomics essentially. But really there’s also a lot of work that’s been going and going into the metabolome. So looking at the metabolites and additionally digging into it a little bit further, so viruses and fungi. So there’s actually not just bacteria that are in play, but also more recently there’s been a discovery that even the viruses and the fungi may play a role in carcinogenesis.
Richard Jacobs: Hmm. So what kind of specifics have you found? I mean, I know there are certain things you can say and certain things you can’t say, but within the realm of what you can say, what kind of specifics can you point out that you’ve discovered?
Gregory Kuehn: Well, as I said, we’ve focused primarily on actually the predictive model. So it’s actually the 30,000-foot view. And so it’s a combination of hundreds of different markers and comparing those hundreds of different markers between the disease state and the healthy state all at once. So the actual specific findings related to the etiology are something that essentially is to be explored later. Actually sort of you can drill down or initiate kind of a one-off study to look at any particular mechanism of action. We’re essentially using machine learning to model all of it at once.
Richard Jacobs: Okay. I mean, how successful has the modeling did, like again, what jumps out at you? What have you seen so far?
Gregory Kuehn: Well, what jumps out really is the incredible opportunity. So because it turns out that this system, this microbial ecosystem that we’re able to measure now for the first time is very sensitive to a situation of colorectal adenomas in carcinomas. So we’re developing tests that may be more accurate than any other existing tests for predicting the presence of a colorectal adenoma for example. And that’s incredibly important because essentially the colon cancer screening program in the United States and around the world are all designed to try to detect adenomas in the interest of trying to prevent cancer. And that’s essentially why you go and get a colonoscopy as recommended. Colonoscopy aims to detect adenoma and most often when adenomas are found, they’re removed via polypectomy. And that polypectomy actually is what has been demonstrated to prevent cancer. And so the problem, however, is that previous, not invasive diagnostic approaches weren’t sensitive to colorectal adenomas. And so, therefore, that led the screen programs to rely so heavily on colonoscopy. But because colonoscopy is so expensive and invasive and there’s a limit in terms of the geographic locations of endoscopy centers. That’s sort of why colon cancer has persisted as being one of the highest cancer killers and is number two. And so what the system really needs is actually a noninvasive test that is sensitive to adenomas and that’s what this technology is hoping to deliver. So we’re kind of assessing the overall health from the perspective of the microbial ecology. And that’s what the paradigm shift and so that’s sort of an indicator of, of disease and it’s enabling us to now select patients that are at high risk for having adenomas or carcinomas. And then we can actually advise those patients to go into a colonoscopy at that point. And it’s sort of get more people into screening programs and ultimately find more colon polyps and adenomas and carcinomas. And the opportunity is actually to completely eliminate colon cancer. That’s how large of an opportunity it is with finding these adenomas.
Richard Jacobs: I mean the colon is pretty big. The large intestine goes all around the stomach and down. Where does it happen typically, like in the sigmoid colon or in the rectum? And when you’re looking at bacteria, I would guess the only accessible places like the proximal colon, right? The rectum and the sigmoid colon, like the rest of the, there’s a lot more colon in there. I don’t know if anyone knows what’s going on in their cause it’s kind of buried.
Gregory Kuehn: That’s true. Most colon cancers all develop in the lower intestine. And actually one hypothesis is that that’s where all the microbes are. But there’s also an incredible amount of other activity going on there. And that’s essentially what is triggering carcinogenesis is a variety of factors including chronic inflammation, potentially Geno toxins that are produced by bacteria. And other factors, their feedback mechanisms that essentially are causing the damage to the genomic DNA that actually triggers the cancer and the most common pathway of carcinoma progression is, that is sort of well understood is that its slow-progressing adenoma, the polyp adenoma to advance adenoma to carcinoma that’s traditionally been understood to be around in about a 10-year process.
However, in the last five, 10 years with the explosion of all these Omics technologies, we’ve actually seen that there’s perhaps as much as 40% of cancers actually start from not advance adenoma. So very small polyps that are sort of jumped straight into cancer. And that has been why there’s been more interval cancer, so cancers that pop up in between the screening intervals of which is recommended every 10 years colonoscopy. But if you have small adenomas that are essentially jumping straight into cancer which is a different pathway into carcinogenesis. And that’s sort of why we may have an advantage as a screening test strategy because we’re picking up on actually the earlier signs of not advanced adenomas in addition to the advanced adenomas and carcinomas. So it’s sort of with the power of the Omics technologies we have a potentially new way of stratifying risks for colon cancer that is going to be a valuable new tool for screening programs.
Richard Jacobs: So again, what have you seen changes if someone does know adenomas, what does their microbiome look like in the colon versus adenomas versus carcinomas? Or whatever stages next, if there is the next stage.
Gregory Kuehn: Well, as I said, it’s hard to pin things on a specific corporate and that essentially is why it’s been a tricky problem. So it’s not as if there are a few bacterial species that are the culprit. It’s actually a system that’s so complex as I mentioned all of these different factors that it’s sort of like looking at the health of a rain forest and actually trying to like understand whether the rain forest is healthy or not. If you look at a few species and genes actually that are present in those species is kind of the view that we’re looking at and trying to extrapolate that to whether the rain forest is healthy or not. That’s how complex the system is. And fortunately, I think that in the situation of colon cancer or inflammatory bowel disease or a situation with colon polyps, you have some significant problems. The signal becomes loud enough actually that you can isolate it with the AI and machine learning approaches. And I think that it ends up looking something like part of the forest is burned down. I mean, so it’s a significant problem with the ecosystem.
Richard Jacobs: Any idea of I don’t know if this factors in, but how often the person that you’re sampling or the creature that you’re sampling goes to the bathroom? I know this is really getting into like literally gross detail, but some people may go to the bathroom like twice a day. They may have a bowel movement, some people will maybe like once a day, once every other day, once every three days, God forbid longer. I would think that might have a hugely transformative effect on their microbiome. Like even when someone’s bowel is empty. What does it look like in the approximal colon versus as it gets filled up with matter and then when it’s full, what does it look like? And then right after the evacuation, what does it look like? I wonder if the microbiome, because of the stuff that’s in there, like radically changes locally and then changes again as it gets fully empties.
Gregory Kuehn: You’re absolutely right. There are many different components that you can look at. So there are daily changes in the microbiome and of course changes with food and about 50% of the genetic material in a bowel movement is microbial and most of the rest of it is from your food. There is actually a stable component of the microbiome that’s able to be modeled over time. And it’s actually been observed you can see the microbiome recovering to a stable state following disruptions such as a course of antibiotics or a colonoscopy or some sort of shocks such as that. But in order to characterize a healthy from a disease state. We’re also doing signal processing and teasing the signal from the noise. So essentially the microbes that change every day to a certain extent kind of our fall out of the model because they aren’t predictive of the disease state. And so that’s sort of what I can say about that.
Richard Jacobs: Okay.
Gregory Kuehn: I guess to add a little bit more, the stable component of the microbiome, it is related to biofilm production. There are pockets that are in the epithelium, the mucosa where these microbes are preserved and essentially they shed out into the lumen. And that’s sort of what we’re measuring.
Richard Jacobs: Hmm. Okay. What do you think are going to be some of the breakthroughs that you’re going to come up with for the next year or two? Or is it going to be much longer-term than that?
Gregory Kuehn: Well, yeah, we are unique as a microbiome diagnostics company in that we are pursuing FDA clearance. And so that’s actually the biggest news of the company is that we’ve received a breakthrough designation from the FDA and that gives us access to the breakthrough devices program. So, which accelerates our path to market. So we’re working now on with experts at the FDA to put together a clinical validation plan and we’re ultimately going to be doing a clinical trial with thousands of patients. So that’s sort of something a new frontier for microbiome testing is getting up to that level of clinical validation. So having thousands of patients that receive colonoscopy as the clinical truth and the histopathology. So having that as a positive versus negative for predictive modeling is very powerful for actually untangling the complexity of the gut microbiome and its impact on health.
Richard Jacobs: Okay. Well, very good. What’s the best way for people to find out more about Prescient Metabiomics?
Gregory Kuehn: We have two websites I can point people to. One is metabiomics.com and another one we just launched is powerofprediction.com which is a website in partnership with our strategic partner, Prescient Medicine.
Richard Jacobs: Okay. So the best thing is what to go to metabiomics.com or is there another resource?
Gregory Kuehn: metabiomics.com.
Richard Jacobs: Okay. That’s the best way. Well very good. Well, Greg, I appreciate you coming back and thank you.
Gregory Kuehn: Okay, thanks a lot.
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