Decoding the Holobiont: The Ecosystem of Ecosystems

June 24, 2026

In this special episode of the Health Optimization Medicine Podcast, Boomer Anderson, Dr. Ted Achacoso, Dr. Scott Sherr, Dr. Allen Bookatz, and Dr. Jup Kuipers explore:

How does the concept of the holobiont change our understanding of the human body from a collection of organs to an interconnected ecosystem?
Why do the trillions of microorganisms living in and on our bodies play such a critical role in health, disease, and resilience?
What are the limitations of traditional organ-based medicine, and how does a holobiont perspective help connect symptoms across multiple systems?
Why does Health Optimization Medicine prioritize metabolomics over genetics when assessing what is happening in the body right now?
How can understanding the relationship between metabolism, the microbiome, and the cell danger response help optimize health before disease develops?

What We Discuss:

00:00 - Introduction: The HOMeHOPe Faculty in D.C.
00:48 - Superorganisms vs. The Holobiont Ecosystem
02:25 - The Shift From Organology to Holobiontology
03:45 - The Blind Spots of Specialized "Organ" Medicine
05:40 - How Statins and PPIs Disrupt Your Cellular Ecosystem
07:30 - Why Clinical Metabolomics Beats Genetic Testing
08:55 - Epigenetic Signaling and the Cell Danger Response (CDR)
10:48 - The "Narcisome" and the Future of N-of-1 Medicine
11:50 - Why Randomized Controlled Trials Miss the Microbiome

Full Transcript:


[00:02:45] Boomer Anderson: Welcome back everybody to a special edition of the Health Optimization Medicine podcast. We're recording here in Washington, DC. We've got five of the six faculty of Health Optimization Medicine. And today we're going to be talking about something called the holobiont. And this was a term that I was first introduced to by two people at this table, Dr. Scott actually first and Dr. Ted, but it's a term that comes actually from a scientist in Germany but was more popularized in the 80s and 90s by a woman by the name of Dr. Lynn Margulis. And Dr. Margulis published quite a bit of work on this. But Dr. Ted, let's go to you. Why did you decide to make this a sort of a core value or a core part of Health Optimization Medicine?

[00:03:33] Dr. Ted Achacoso: It's because I was looking for a model of the body as an ecosystem. And I was looking at the concept of a superorganism first. And a superorganism is something that has the same gene set but different expressions of the phenotype or the physical characteristics in a lifetime. An example of that is slime mold, right? So it grows, it has a fruiting body, and then gets back into the spore. So its entire life cycle, but it is all driven by a single gene set. Now, holobiont, which is what I was looking for, was going to include all the microbiota that we have. So we have about 19,000 plus genes in the body, and we have 20 plus million genes actually recorded, and that's because we have a lot of microbiota, mostly in our gut. But now we have found that there are actually microbiota in our cornea—they're not really sterile. In our ureters, they're not really sterile. And in findings a few years ago, the placenta also has its microbiota. So we can see that we are actually an ecosystem of cooperating and competing organisms in the body. So much of the body is in cooperation. And when you don't treat your microbiota right, especially your gut microbiota, which is about 76% of your microorganisms, and they are treated separately as an organ. If you don't take care of them, they will actually not take care of you.

[00:05:00] Dr. Scott Sherr: What's the... I think it's around 15 pounds or what's the amount of microbiota we have in our gut? It's something around that, I think?

[00:05:07] Dr. Ted Achacoso: It's about four kilos. Yeah, four kilos. Okay.

[00:05:10] Boomer Anderson: All of us at some point heard Dr. Ted talk about the holobiont. And when we talk about perspective shifts within Health Optimization Medicine, there are three, but one of those is that shift to that holobiont perspective. Does anybody want to explain what that means from a clinical standpoint?

[00:05:27] Dr. Scott Sherr: I can take that one to start off with, and I think it's important for all the three of us docs here—we have an ER doc here, family medicine doc, and of course Dr. Ted. But in respect of how we learned this from you, which was that in medical school we learn about the heart, the lung, the brain. We don't learn that there's a basic building block of all of them, which is... when I met Ted in 2017, he was like, "Well, there's a basic cell that runs everything." I was like, "It's almost like the ring that rules them all in Lord of the Rings." And the shift is from what Dr. Ted has called organology to holobiontology, right? The idea that we're this holo-organism in the way that he described. And that was a big shift for me when I first learned about it, because it made a lot of sense, right? Because it's not like you just have a heart, or you have a lung; you have the basic aspect of all of this. What was your sense of, Allen, this when you first started learning about it and how it would represent to you as an ER doc? You're not thinking about the whole organism so much sometimes, right? You're thinking about like keeping somebody alive and, you know, keeping their blood pressure up. But what resonated to you?

[00:06:30] Dr. Allen Bookatz: Yeah, I think what stood out is that many times someone might come into us seeking care. They're depressed, they're also complaining of bloating, they don't feel well. And, you know, we say, "Oh, for your depression, let's get you an SSRI and get you to a psychiatrist." And mental health is really important and undervalued, and certainly that might be part of their care plan. And then for their bloating and their chronic GI distress, we're going to refer them to a gastroenterologist, right? And each of these specialties... what's wonderful is that they have a very, very detailed lens through the illnesses that they understand and operate through to try to diagnose and treat what's happening. But rarely do they consider how one system is affecting the other. And so the shift, the mindset shift and the practice shift for us as physicians, clinicians, is we now would look at someone that has, say, a mood disturbance, depression, and inquiring, "Hmm, tell me about your bowel habits." And it would lead us to look at the concept of, "Okay, this holobiont picture would say I am now going to look at this from the frame of an ecosystem. This person is an ecosystem of ecosystems, and where is there an imbalance?" And so what we might uncover is someone that has gut dysbiosis and/or some type of chronic maldigestion or inflammation within their gut, which affects their immune system... So they might have a whole host of other symptoms like rashes and fatigues and either immune over- or under-activation, by which they'd probably have a rheumatologist or an allergist that they'd be going to and getting steroids. That would be missing this picture. But if we look at it through the HOMeHOPe lens, then we're going to understand that the gut has one of the largest supplies of serotonin receptors in the entire body, and we know that there's this super, super important interface between the microbiota and their relationship to how we might be feeling.

[00:08:25] Dr. Jup Kuipers: I guess I agree with Dr. Bookatz on this one. What really was an eye-opener for me as a family medicine doc, we often prescribe these medications to alleviate symptoms of different organ systems. Say we prescribe statins for high LDL or PPI for acid burn. But we failed to realize that these have effects on all the cells of your body, which are fundamental to all the organs. And yes, they have good effects on one organ, but they can actually negatively affect your whole ecosystem of cells. For example, statins reduce your CoQ10 stores, which makes it much harder for you to produce energy, or PPIs reduce your acid burn but they also make it harder to absorb all these nutrients which feed all the cells in your body.

[00:09:10] Dr. Scott Sherr: And then might kill you.

[00:09:12] Dr. Jup Kuipers: Actually this guy here, yeah. Might die from that.

[00:09:15] Dr. Ted Achacoso: Yeah, I have genes that are too lazy to metabolize PPIs. Just as a note to clinicians, the way to think about this is that, thinking of what you're looking at when you're testing antibiotics or surgical techniques, right? Your individuals of a population make up your population. Are other people, right? So that's your ecosystem. So in Health Optimization Medicine, the cells actually that form cellular ensembles is your population. So it's the same idea, it's just a different ecosystem, a smaller one, so that in Health Optimization Medicine, the entire body of the person is your ecosystem and therefore is your holobiont, right? And in clinical epidemiology and other parts that study diseases among populations, then your population is actually the people that are included in the cohort. So these are same ideas, right, same principles. It's just reduced to you, right, as a single person.

[00:10:15] Boomer Anderson: Ted, I have a question for you. So we went from organology to holobiontology. And then from there it like, how do you test the holobiont? And you found this field that had been around for a long time called metabolomics. Why did you end up deciding that metabolomics was the best way to look at the holobiont?

[00:10:33] Dr. Ted Achacoso: Because I got so frustrated in our fascination with genetics, which can only tell you what can happen, right? And we are so DNA-centric, and I think it's because of our focus on what is in the center rather than what's going on in the background. And I wanted to ask, you know, what's going on now? How can this metabolism be remediated if they can? And that's where I actually took a look at clinical metabolomics. At the time, there was also transcriptomics, you know, which is what appears to be happening. There's proteomics, which, you know, is what makes things happen. But still didn't answer what's happening now. And metabolomics has been around 40 to 50 years. They're finding their use now in the clinics, but illness medicine doctors like us before we did Health Optimization Medicine, you know, really did not understand that everything is in a spectrum before you actually get into disease. You have subtle toxicities, borderline deficiencies, which can be addressed at the time. You know, many people do not even realize that your sex hormones are actually metabolites of cholesterol. So when you look at this, you begin to look more upstream. And when you take a look at these values, you see that everything's correlated, right? You drop the cholesterol and all the values below the metabolites actually also start dropping. Like my joke is that, you know, we dropped cholesterol with statins 50 years ago. 25 years later, we had to invent Viagra.

[00:11:40] Dr. Jup Kuipers: I think because for most docs, metabolism is still maybe a bit of a vague concept. And what was a real eye-opener for me is that it's more than just this process of catabolism and anabolism building. But it also has a signaling function. It's actually the metabolites that signal your DNA through epigenetics to switch on or off certain genes. So the genes we thought were like the primary thing are just your capacity for building, but it's actually your metabolome that decides what gets transcribed and which proteins get produced.

[00:12:30] Dr. Ted Achacoso: Yep, makes an important point here actually, because we focus on the resolution of what's called the cell danger response, which is another topic altogether. But I'd like to say here that metabolites are the primary drivers of the cell danger response. And if you could quell the cell danger response early in any event, right, through the life cycle of a person, then that person's likely going to be healthy. Not necessarily live longer, because living longer is just a byproduct of good health, right? So we're not after longevity, we're after the quality of life. So if these are the drivers that you can actually handle and optimize, then you would probably have a very nicely healthy cell danger response for everything. It's just like when you're a runner, you know, when you get winded, you get back immediately to form, right? So an athlete would actually rev up his heart rate and then when he stops, it will stop right then and there. And that's how we actually want this human cell to be.

[00:13:30] Boomer Anderson: Scott, do you want to wrap this up?

[00:13:33] Dr. Scott Sherr: Yeah, I mean one final thing that I always, that you showed me a paper a long time ago, Ted, about something called the narcisome. Which I liked. The idea is that over time, we're measuring genetics, we're measuring proteomics. I was just talking to another company, another guy that's using proteomics in practice. Transcriptomics, metabolomics, your epigenome. So eventually it's going to be some sort of chip that some of us are going to get implanted right here that gives us all that information on a real-time basis. But right now, we know that we can use metabolomic data to help us right now. And that's the crux of what we do, right? Because the holobiont is the holo-organism that is you. And you're not going to be the same, I'm not the same as boomer by any means, you know, or Ted, or anybody, right? Everybody's different. And that's why when you look at the, I think Ted you've talked about this right, the best studies out there now are the N of 1 studies, right? Because it's just your holo-organism that is you. And so that's where things are going. Randomized placebo-controlled trials, these things last for a couple years and then they say something's different. That's your favorite thing about, you always like to make fun of those trials, right?

[00:14:35] Dr. Ted Achacoso: Yes, because when they ask me, "Oh, is this randomized controlled trial?" They control for everything. I say, "Did they control for the gut microbiome?" And the answer is no, right? And that's where they saw in a study why a certain oral cancer treatment failed. It's because of the lack of two organisms in the microbiota. And that was the last place where they looked.

[00:14:57] Dr. Scott Sherr: Yep, yeah. And so, well thank you all for listening to another episode of the Health Optimization Medicine podcast. We hope you all enjoyed it. Many more to come. Thank you all for being here in person everybody. See you next time.

[17:21:19] Boomer Anderson: Namaste.