METABOLOMICS Reveals What Others Miss

Episode 270 — METABOLOMICS Reveals What Others Miss

August 28, 202535 min read

Guest: Dr. Paniz Jasbi • Date: August 28, 2025

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Episode Overview

Metabolomics is a cutting-edge way to see what’s really happening inside the body - beyond what genetics or other tests reveal. In this episode, Dr. Paniz Jasbi explains how metabolomics identifies real-time imbalances and helps parents move from guesswork to clarity.


About Dr. Paniz Jasbi

Paniz Jasbi, PhD, is the Co-Founder and Chief Science Officer at Theriome and a systems biologist specializing in mass-spectrometry–based metabolomics. He completed his PhD at Arizona State University, later serving as a Postdoctoral Research Scholar in the School of Molecular Sciences, and has authored peer-reviewed work linking metabolomic signatures to aging, neurocognition, and microbiome-related health. At Theriome, he leads development of the Aristotle Test, a next-generation metabolomics panel designed to translate complex biochemistry into practical, personalized recommendations for families and clinicians. Dr. Jasbi also serves as the Director of Metabolomics for the American Board of Precision Medicine.

https://therio.me


You’ll Discover

  • What Exactly Is Metabolomics? (3:11)

  • Why Genetics Alone Doesn’t Tell the Full Story (7:32)

  • How Metabolomics Validates What Parents Already Notice (14:10)

  • How Theriome’s Aristotle Test Stacks Up Against the Organic Acids Test (20:22)

  • How Digital Twinning Pinpoints the Most Effective Actions (27:01)

  • A Major Root Cause Seen in Children With Autism (40:56)


Referenced in This Episode


Full Transcript

Len Arcuri (00:01.623)

Hello and welcome to Autism Parenting Secrets. If you're a parent navigating autism, this episode, like all episodes, is exactly designed for you. Because families are often overwhelmed by especially all the tests out there. But too many leave you with more questions than answers. Today we're talking about a powerful new way to see what's really happening inside the body. It's called metabolomics and it reveals what other tests often miss.

My guest is Dr. Paniz Jaspi. He's the co-founder and chief science officer at Therium. He's a systems biologist with a PhD from Arizona State University, and his research has linked metabolomic patterns to aging, cognition, and the microbiome. At Therium, he leads the development of the Aristotle test, a next generation metabolomics panel that translates complex biochemistry into practical.

personal insights for families and clinicians. The secret this week is, metabolomics reveals what others miss. Welcome, Panisse.

Paniz Jasbi, PhD (01:11.192)

Thank you so much for having me Len, it's a pleasure.

Len Arcuri (01:13.953)

Well, I'm excited for this conversation. It's been a long time in the making. We talked, I think, about 18 months ago initially, and I know you've been refining and formalizing this test. I'm excited for you to be able to share what that test captures and how it might help parents who are listening for their child. And I also know it's a passion of yours in terms of this space. So let's just rewind and start off with...

metabolome or the metabolomics, can you explain contextually why focusing on the metabolome as opposed to let's say the microbiome or other ohms that might be out there, can you just give a level set of what are we talking about and how is it different?

Paniz Jasbi, PhD (02:01.71)

Yeah, definitely. So metabolomics is a new strata of systems biology. It was really coined as a first term and served as its first use cases in the summer of 1999. And

You probably have not heard of it or if you have you've heard of it in passing or maybe hushed whispers and and it is something that for the last I would say, you know 25 years it's been around has absolutely revolutionized science and Maybe in the last five years or so we have started to see the translation of metabolomics from bench to bedside And what is metabolomics? That's a really great question

I think your viewers and most general lay audiences are familiar with other layers of omics like genomics, microbiomics, transcriptomics, and these ohms, these denote an entire set of something and their dynamic interactions. So genomics is concerned with the comprehensive set of genes and their interactions. Same thing with proteins. Proteomics is concerned with the comprehensive set of the protein complement and those interactions.

Same thing with the microbiome. And so the metabolome is focused on the entire set the study of metabolites and their interactions within a system that system can be an animal a cell's line it can be human it can be wastewater that's being analyzed and We apply special statistics and bioinformatics to derive what is happening in that system so metabolomics and and we can give

comparisons to genomics and that can tell you a little bit more about what the process of our testing entails. But it's looking at not what is happening. It's looking at what is happening, not what could be happening. It's not looking at potential, like genomics. It's not looking at the proteins, which are often very much delayed temporally with respect to phenotypes and environmental exposures and everything else that's related into the etiology and progression of...

Paniz Jasbi, PhD (04:16.694)

autism. Metabolomics is looking at exactly what is happening. What is currently being expressed? What is the current dynamic health state of this system? And then in this context, it would be a human, right? That is what metabolomics is really good at. What we look at when we see, you what are the biggest contributors to human health and mortality? You know, so we're talking about cardiovascular disease, neurodegenerative diseases, cancers. These are not

genetic tests and genetic diseases in that there's you know a handful of genes that invariably You know will cause the phenotype of cancer or Alzheimer's or cardiovascular disease. What we see is that these are heterogeneous in their ideologies they are a a mixture of the genetic environment as long Along with this interplay with environmental cues. So they're heterogeneous

And that's exactly where metabolomics sits in the hierarchy of systems biology. It sits directly at that intersection, at that nexus point between the genes and the environment. So if we want to test for conditions that are caused by a interaction of the genes and the environment, metabolomics provides an incredibly attractive layer to probe because the answers usually lie for heterogeneous diseases in this metabolomics layer.

Len Arcuri (05:39.805)

Well, thank you. That's very clearly identified. And again, even for me looking at it, it's helpful in terms of where sequentially are we focusing because you mentioned genomics. I know a lot of our listeners maybe have done functional genomic type testing for their child. And again, that doesn't reveal anything about what's happening now. That's just your blueprint, how you're set up, how you're wired. And so the metabolomics focus is really, as you said, on that interplay of

your blueprint, how you're wired with how it's reacting to the environment. So it's basically, if you're wanting to focus on the epigenetics, like the interplay of genetics and the environment, it's really this metabolome that is where you really want to focus to see what's happening when those two meet. Is that fair?

Paniz Jasbi, PhD (06:29.568)

Exactly. So when we talk about the genetic architecture of autism, what we see for instance, really, and this is why genetics I think gets a lot of importance, because it is highly heritable, autism, right? Twin studies show that anywhere from 60 to 90 % of autism has heritability, but there's no single autism gene. And when we take the polygenic approach, we see that hundreds of genes contribute risk.

Most of them individually are small in effect. And there are rare variants in about 10 or 20 % of cases. Autism can be tied to identifiable mutations or other syndromes like Fragile X or Rett syndrome, TSC1 and 2, P10, SHNK3 mutations. And these are relatively rare, but still clinically important. And there's also common variants. So when we look at large, what we call GWAS studies, genome-wide association studies,

Len Arcuri (07:18.53)

Mm-hmm.

Paniz Jasbi, PhD (07:25.368)

They show many small effect variants in synaptic function, neuronal signaling, chromatin remodeling. And there's also some de novo mutations, right? So sometimes new mutations that are not inherited, these mutations that are key in neurodevelopmental genes, they arise spontaneously. And we see this especially in families with no prior history of autism. So genetics on the outside seems like...

That's the layer I want to probe because there's a lot of genetic links. And so maybe I should look there logically. And you're not wrong in thinking that. The scientists looked at this for 20 odd years. And ever since the completion of the Human Genome Project, we've failed to get the answers we want. And there's a distinction about what genetics explains and what it doesn't. So genetics, we're looking at susceptibility. It highlights certain pathways like synapse formation or calcium signaling, chromatin remodeling.

that are important in autism, but genetics alone does not explain severity, it doesn't explain comorbidities or trajectories, and those are shaped by metabolic and environmental context. So that's why no two children with the same genetic variant can present really with very different autism trajectories. So is there worth in genetic testing? Yeah. So clinical genetic testing, you know, currently it's usually done through microarrays or exosome sequencing.

This is recommended in some autism guidelines, especially if features suggest a syndromic disorder. But the diagnostic yield is dismal. About 10 or 20 % can be a little bit higher if dysmorphic features or seizures or strong family history is present, but it's only 10 to 20 % diagnostic yield. And it really helps in management when a clear syndrome is found. For instance, if there's Fragile X, you can do reproductive counseling or Rett syndrome. There's Cardio...

pulmonary monitoring that's usually recommended, but there's way more limitations that need to be discussed. So most children with autism, about 80 to 90%, will not get a definitive genetic diagnosis. And the results will often come back as variants of uncertain significance. And it doesn't usually change day-to-day management for families. And this is exactly where metabolomics adds values. So genetics will tell us about the risk and the blueprint, but the metabolomics tells us about

Paniz Jasbi, PhD (09:47.032)

the real-time function, the phenotype. So a child, for example, may carry a mild genetic variant in a mitochondrial enzyme. Genetics can't say if it's causing problems, but metabolomics can reveal if energy metabolism is actually impaired. And so that's why many researchers now advocate for these multi-omic approaches. So pairing genomics or the potential with metabolomics, the actual. And so for parents, I think the distinction should be key, right? Like as we say,

Genes load the gun, but metabolism pulls the trigger.

Len Arcuri (10:20.205)

Okay. I appreciate you sharing all that. And yes, I'm nodding in agreement, especially, I guess I'm curious about a couple of things before we dive into metabolomics. Number one, I'd be shocked if it's 80 to 90 % because again, like in terms of people where there's some genetic underpinning to a child who's been diagnosed with autism, seems like in my mind it would be much smaller. don't know. I haven't run into many parents who they have some genetic.

You know information like that. It's it's a it's much it's much more likely. Hey, there's nothing significant You know when people do that genetic test, but then they do the functional genomic work looking at the 20,000 genes and you know Not that we're trash talking that that could be extremely useful and important to understand how art how are you wired? How is your child? What's their blueprint? It's just is that enough and the question is okay. Well, what ultimately if you have that information, what can you do now?

And that blueprint in what ways is it showing up and manifesting in ways that you'd like to change. And that's where, again, that information is useful. But what you're going to be focusing on is up until a couple of decades ago, we didn't really know about the metabolome. Right. So, so now that we do, how can we understand that? And, and, and I guess you've, you've really dedicated yourself to solving the problem. How can I test and assess?

how the metabolone is functioning in a detailed way that might actually result in very specific pinpointed suggestions for people to do something about it.

Paniz Jasbi, PhD (11:58.37)

Yeah, exactly. And just to clarify, that 80 to 90 % I mentioned was actually saying that 80 to 90 % will not get a definitive genetic diagnosis. yes, yeah, only about 10 or 20 % of children get a clear genetic explanation. Even then, genes don't predict how a child will grow or learn or respond to interventions. Yeah. Sure.

Len Arcuri (12:09.473)

Right, right, no, I get it, I get it.

Len Arcuri (12:19.245)

And I'm even questioning that. think that's high. I think it's a much lower percentage, but forget about what I think. But otherwise, again, this is not about trash talking, any particular type of diagnostic testing, genetic testing, functional genomic testing. And we've had a lot of great dynamite practitioners who provide that service. Great. These are all pieces of or tools that you could use to figure out what's happening right now.

Paniz Jasbi, PhD (12:30.925)

Yeah.

Paniz Jasbi, PhD (12:39.214)

Yeah.

Len Arcuri (12:46.657)

with my child. And I think what's exciting about what you're diving into is that this is a radically different way of even assessing what's going on and much more potentially powerful in the sense that it's really focusing on what's happening now as opposed to how you're wired or how you're set up.

Paniz Jasbi, PhD (13:06.336)

Exactly, exactly. I think, and again, we, as I said, a lot of people are proponents for this multi-omic approach and we are as well. We offer other layers of omics testing. Metabolomics happens to be our flagship layer. And I think it's really valuable. I hope for your readers to know this and maybe consider metabolomics. I think when I speak to parents of children with autism,

they already sense that autism is whole body, right? Like they are already noticing gut issues, food sensitivities, sleep problems, fatigue, anxiety, immune challenges in their autistic children. And these standard genetic or neurological evaluations don't explain these whole body issues. And I think when they receive their metabolomics, there's a sense of validation. Metabolomics validates what parents are already suspecting that autism

isn't just in the brain, it's connected to metabolism throughout the body. what metabolism shows is a functional picture. Again, the genetics show risk and lab panels will show snapshots, but metabolomics shows function in real time. How energy, neurotransmitters, gut microbes, detox and nutrients are actually working together. And I think...

Len Arcuri (14:04.045)

Thanks.

Paniz Jasbi, PhD (14:26.568)

When we review these panels, when our clinical liaisons review these panels with parents of children with autism, it shifts the conversation from your child has autism to here's how their body is functioning differently and here's what you can support. And it makes the invisible visible.

Len Arcuri (14:42.613)

and keep the community in support.

It's like, here's how your child's functioning that ultimately is getting labeled as something that we call autism, which is why, you know, it's really about moving away from that label, which really has very little utility and like, Hey, here's what's actually happening. And again, with that information, it reveals so much that you can do to influence, to meet your child where they are, to help them thrive in a very pinpointed detailed way, which you're right. Basically.

will validate all the reasons why you're wanting to clean up the environment, why you're wanting to eat less toxic food, all those interventions that you kind of hear about, it kind of brings it all into greater clarity why specifically those interventions are worth for potentially your time and effort.

Paniz Jasbi, PhD (15:36.014)

Exactly. And I think parents and practitioners, let's not leave the practitioners out of this because they are working oftentimes with ambiguous data. their parents and practitioners are both getting overwhelmed because so many interventions are trial and error. But metabolomics coupled with our digital twinning, which I can explain what that is, this helps cut through the guesswork by highlighting which pathways are off balance. For example, we can ask, is hyperactivity in my child linked to low GABA?

fatigue in my child tied to their mitochondrial energy production is irritability in my child connected to gut microbial metabolites. And instead of treating every child the same, metabolomics points to these personal starting points. parents who've done our testing, has really, these reports have guided conversations with their clinicians. I think to be honest, parents often feel dismissed when they bring up gut issues, diet or supplements.

and having this hard biochemical data to speak with their clinician about gives them confidence and even the language to bring into those appointments. And if the clinician is new to metabolomics, which is very likely, these concrete markers can still lead to a very constructive dialogue. And I think metabolomics, it delivers hope without false promises. This test doesn't diagnose autism. It certainly doesn't cure it.

What it does is show where the body may be struggling and those areas are often modifiable through diet, environment, and supportive care. And again, for parents, it just reframes autism from like this fixed identity to a condition with metabolic dimensions that can be supportive.

Len Arcuri (17:17.517)

Okay, super. that's well phrased in terms of what the opportunity is here. And I think most of our listeners are aware, right? They're aware of the whole body approach. They're aware of more functional approach makes sense. And everyone may be at different stages for sure, but I know most of the listeners probably are aware of a lot of the routine tests that you might do. When I say routine,

If you're working with a MAPS type practitioner or functional medicine type practitioner, there are some tests that, you know, pretty much most of those professionals, not conventional pediatricians, but most of those professionals might recommend like a stool test, like certain urine tests. But the one I know that's almost viewed as kind of the gold standard within this community of, within autism or biomedical is the organic acids test. And, and even when

The journey started with my son, you know, almost two decades ago, the organic acids test has been, had been around for a while and it was viewed as the cutting edge report. You know, now 20 years later, it's still widely used. There are many practitioners who confidently trust that that's a meaningful report and they're very skilled at helping, you know, parents to figure out what's in there and what changes they can do. so.

without again wanting to trash talk that report, it is quite old. Technology has evolved tremendously. talking about how your report and focusing on a metabolome could actually be placed using the OAT test for a parent. I know that's something that you've, you know, you're confident with. Can you explain more why you're confident that this testing is more reliable, accurate?

actionable, useful. If you can expand on that, just know a lot of parents would love to hear that side-by-side comparison.

Paniz Jasbi, PhD (19:18.712)

Sure, yeah, so the OAT test is a great test. And companies that run the OAT test, like Great Plains, like Mosaic Diagnostics, these are great companies. And the integrative and functional medical practitioners that use them are great practitioners. What it does, just to recap, it surveys roughly 70 urinary organic acids that map broadly onto energy metabolism, neurotransmitter metabolism, gut dysbiosis, detoxification, and oxidative stress.

and certain nutrient deficiencies. It's mainly looking at, when we talk about pathway level, it's mainly looking at Krebs cycle intermediates, fatty acid oxidation, catecholamine and serotonin metabolites, microbially derived metabolites like arabinose, tartaric acid, 4-hydroxy phenylacetic acid, glutathione-related metabolites, oxalates, and B vitamin-dependent intermediates. So I always get this question, how does our test compare?

The Aristotle panel measures 126 sentinel metabolites. So these are appearing through numerous pathways. We're able to cover roughly 70 % of all human metabolic functioning. And critically, these are the biochemical domains that OAT claims to assess. But we have better specificity because we validate on dry blood spots and not just urine. Urine is an excretory profile, right? So it's not a systemic profile and it's

doesn't have as many implications as analyzing blood. So what we look at is energy metabolism, the TCA cycle. We quantify citric acid, sassinic acid, fumaric acid, malic acid, alpha-Kg, and a bunch of intermediates like cis-acatenate or isocitrate. And these overlap fully with the Oats mitochondrial markers. And they go further by contextualizing these with science-derived, literature-derived mitochondrial health score. We also look at the B vitamin path.

We're looking at niacinamide, adenine and guanosine nucleotides, and sarcosine, which is a main methylation donor in the human body. And these, again, provide higher resolution data than these indirect OAT functional markers for things that are like riboflavin and niacin and folate. We're also looking at neurotransmitter metabolism, GABA, serotonin, taurine, glutamate, homocarnosine. And OAT, conversely, uses downstream metabolites of these in urine.

Paniz Jasbi, PhD (21:41.612)

like homovanilic acid or VMA, and they're using proxies, whereas our panel is directly measuring these key neurotransmitter metabolites in blood, making a much stronger inference. Oat looks at gut microbiome dysbiosis markers a little bit differently. We're quantifying tryptophan metabolites and all those indole derivatives. We're quantifying diamino-pamelic acid, which is a very important marker of bacterial cell walls. We're also

analyzing cadaverine, putrescine, spermidine, and its chemically structured cousin, spermine. And these are directly capturing microbially derived metabolites, exactly what oat markets, arabinose, and their 4-HPAA marker for. And so this is actually a space where an ASU researcher, Professor James Adams, has done some work with us last year in collecting some of this metabolite for...

for his really interesting autism-derived tests and fecal microbiota transplant protocols. And so we are tied to some of this autism research. then lastly, I would say that as far as detox, we are able to look directly at glutathione, cysteine, cystothione, methionine, uric acid, oxygluteric acid, fumaric, and malic acids again. And these offer really superior coverage of redox balance compared to Oats' single.

oxalate and pyroglutamate marker. So in short, would say our analysts already encompass and improve upon the biochemical coverage of the OAT test. And the Aristotle test effectively replaces OAT with, you know, stronger clinical interpretability because we integrate systems biology and provide 12 health domains instead of a laundry list of abnormal metabolites. And the only minor gap I would say is that OAT has some really niche markers like HVA and VMA, which are showing like

dopamine and norepinephrine turnover and certain fungal sugars like a rabinose. And these are less specific and in practice I would say our microbial and neurotransmitter metabolites are more actionable, although those are nice markers to have that oat has that we don't have. But I get asked this by clinicians all the time, do I still need oat if I run the Aristotle? And the honest answer is no. The Aristotle panel subsumes oats clinical categories and really provides a more rigorous blood-based systems view.

Len Arcuri (24:01.805)

All right, great. Well, again, I know you're confident with what you've developed and I think with a lot of the biomarkers that you mentioned that are in your test are also in the OAT test. And again, the key is those biomarkers, what's behind it in terms of how accurate, is it a proxy or is it something that you're actually measuring as you mentioned? So I think that is definitely something to consider. And I think whether it's

this type of testing or any testing, my pet peeve with a lot of testing is, it actionable? Is it something a parent can actually receive the report, digest it, and actually then take action and feel good about what they're doing? Because I think a lot of tests, including the oat for some parents, creates more stress and more confusion. So a lot of it comes down to whatever test you're running. The key is the practitioner that ordered it, can they help you interpret it? And is

the ultimate actions that you could potentially take to address the outliers or what the report reveals. Is that clear to you? Is that something where you can walk away with some confidence about what to do? And I know your test is kind of geared to get right down to the specific recommendations, almost where your practitioner, their input would still be valuable, but you've designed it in a way where it's something that...

even though it's lengthy, a parent can read and actually understand and kind of move to that stage of taking action to evaluate whether they're going to take action with more clarity than I think. A lot of tests leave that kind of up in the air and that can be a source of stress.

Paniz Jasbi, PhD (25:43.618)

You're exactly right, Len. We've designed this to be a scientific tool. And in fact, it's structured in some ways like a scientific manuscript, where there's an introduction, there's a method section, there's results, there's a discussion section, which can be interpreted as the protocol. So what we do is we take these 126 markers, again covering 68 % of human metabolic pathways. It's very great coverage. And then what we do is we construct a digital twin of this person.

This digital twin serves as a safe testbed, if you will, in a simulation environment. We then take our digital twinning database, which is an intervention of more than 1,300 things that somebody might do, interventions. What do I mean by that? It could be a dietary change, an exercise routine change. It can be a supplement. It can be a more experimental peptide, perhaps, that they might procure through their physician.

Len Arcuri (26:25.357)

Thanks.

Len Arcuri (26:40.557)

It can be a sort of happy thing.

Paniz Jasbi, PhD (26:40.586)

It can be as the totality of things that we have mined, certain statistics from the literature for, to let us know how much of an effect it would have, what the directionality of the effect would be, if it's good for this person, if it's bad for this person. And we take each of those interventions, all 1,300 plus, and we simulate each one 1,000 times on this metabolic model. And what we're observing is the response to this intervention by the digital twin metabolic model.

cross-averaged across every 1,000 iterations. And those 1,000 iterations are not the same. So we're not going to take niacinamide and give it to you, know, niacinamide, you know, mononucleotide, NMN, 1,000 times same dosage, same time of day, same frequency. 85 % of those interventions parameters, so things like how much should I take? What form should I take? How long should I adhere to this protocol? When should I get retested? All of these things are being simulated.

1.3 million times on the digital twin, we're observing the feedback. What we're then allowed to do is collate those interventions from those predicted to be most effective to least effective to even those that are predicted to be detrimental. And then we're able to populate a protocol for each one of the 12 health domains that we monitor to say, you have a poor mitochondrial score because of inefficiency of cofactors.

you have low niacinamide here. We're going to give you 250 milligrams of nicotinamide riboside version for, you know, twice a day, once in the morning, once at night, and you're gonna do this for 12 weeks. It's very specific. This is what we call a personalized protocol. This is truly bespoke. When we see personalization used in the field, oftentimes it's just a buzzword, and it's usually done with simple stratification. What we are doing...

is simulating these interventions thousands of times with slight changes each time to then be able to confidently say, for you, the best form of niacin is nicotinamide riboside. And 250 milligrams split doses between morning and night is best for your digestion circadian rhythm profile. And you're going to do this for 12 weeks because this is where we would think your niacinamide pools would regenerate, your niacinamide nicotinic acid would regenerate to sustain

Paniz Jasbi, PhD (29:02.35)

its cofactor function in the TCA cycle. These are the biochemical inferences we can make, and this is what the report shows. So you'll clearly see on your report, take this much of this for this long, for this purpose. This is the metabolic aberration, the score in your report on the previous pages. This is exactly what we're addressing with this intervention. So you will get anywhere from 12 to 36 things ranked in order of importance for you to do to improve very specific metabolic aberrations that are reported

on the front end of the

Len Arcuri (29:34.881)

Got it. No, great. Thank you for that. And yeah, that precision, that specificity, particularly, let's say, within the autism community, right? B12 is an issue and B vitamins are kind of an area of focus. So your report is going to not only identify that, but then specifically the form and the specific, it's going to get to much more of a granular level rather than just kind of generic recommendations. And then on top of that, it's not as if you're recommending

these particular supplements or these particular interventions, and then you're selling those supplements as well to people. this is all just a diagnostic tool with great specificity in terms of what to do, how much, how often, and there's very specific forms.

Paniz Jasbi, PhD (30:07.63)

Great. Yeah.

Paniz Jasbi, PhD (30:19.846)

You're absolutely right, and that's a point that I forget to mention, but it's something we do deliberately. We are a testing and information company. We are here to allow you to use these tools that are available to us in the university space.

Right? So our company was born out of Arizona State University. We're not owned by them. It's a private company, but it was a spinoff my co-founder and I had developed during our time as postdocs. And we realized that we have these next generation sequencing machines. We have these mass spectrometers. And we have advanced bioinformatics that most people are not able to access. Because honestly, only the best hospital systems in the world

have these tools, right? They're either research use only and they're sequestered in the halls of academia or they're in the Mayo Clinic and the Duke University Hospital system and the Cleveland Clinic. They have their own systems biology course, but to access them you have to be a patient there, right? So what if we could bring these tools to people? And one thing we thought early on was that we do not want to sell anything in the report. We think that that's very disingenuous. We don't have like a

a shell company that comes out of the woodworks either and tries to sell you on these peptides and these supplements and health coaching and diet weight loss or whatever it is. We are giving you the information from the scientific literature, having mined so many studies and we're continually mining and updating our statistics and the interventions in that database. Our goal was to be able to say, you can leverage these technologies that would otherwise be out of your reach and leverage these analyses that otherwise you would

have no access to and they'll just be sequestered in academic papers. And you can use this to get genuine answers on your biochemistry. And we promise we won't hit you up and say, hey, here's a specially formulated bottle for you, Yeah.

Len Arcuri (32:11.149)

Right. Great. That makes sense. Now, the obvious next question that I have is for a parent who actually understands this says, okay, I'd like to see what this test says about my child. People can go directly to you and get the test, would you, what's your normal protocol in terms of, do you recommend that parents do order the test?

that they are working with some medical practitioner to help them with it? Or is it really designed to be for the parent? It's clear enough that you can move forward. Like what's your general guidance for people who, and by the way, the test is, you've been developing it, early. Unlike other tests, there's more of an investment with this test. It's new technology. And over time, you know, this testing will become more affordable and accessible. But for now, if a parent does,

invest in the Aristotle test, what kind of guidance do you give in terms of whether they should be working with a medical practitioner for their child?

Paniz Jasbi, PhD (33:14.03)

So the test is layered, where the early parts of the test, the first few pages, are usually summaries, giving domain level, pathway level, function level explanations that are interpreted by anybody, whether it's a physician or a parent who may be non-technical.

As you go into the report, more and more of the harder biochemistry is unveiled. The report is 70-something pages long. The end pages are usually just for, I mean, the actionable parts of the report, the things that you want to see digest, understand, and implement, that's the first 15 pages. Everything else goes into detail one by one for each metabolite, and that's really where physicians might have more interest.

So my recommendation is to parents, if you do not have a physician you're working with, this test is 100 % able to be administered at home. One thing that we, again, my co-founder and I, we're really adamant about is every test that we bring to the market, whether it's our metabolomics test, our microbiomics test, or our upcoming whole genome sequencing, these all have to be remote patient monitoring enabled. So we should be able to collect the sample by the patient.

minimal or no technical expertise at their kitchen counter. That's the litmus test. You can take this test on your own. You can send it in on your own. The results are interpretable on your own. And you can implement the protocol on your own. Where does the physician come in? Because we do a lot of AI. We have a lot of really fancy data structures. But we are not looking to, nor is it our goal to replace the physician. We don't think we can do that.

we see the best outcomes in parents that are working with a physician. We see the physician's tacit knowledge, decades of practicing medicine does accumulate a tacit knowledge that AI just can't replicate yet. And so we see their knowledge, their deep domain knowledge modify and guide and help identify the biggest leverage points on that report for that child. And parents usually have better outcomes.

Paniz Jasbi, PhD (35:26.454)

Again, it's really easy to do, to take the test, to send it in, to receive the results. It's very transparent and linear, but physicians often apply a degree of interpretation that only comes from knowing that child, from medical examinations with that child, interpreting their metabolomics panels in the context of other tests they have performed on that child. And oftentimes that mosaic approach, again, just yields better outcomes for parents.

Len Arcuri (35:55.287)

Great, beautifully put. I think that resonates with me. And I actually think something like this, a new kind of groundbreaking test, kind of radically different than what might be available now. If you do order this and present it to your practitioner that you're working with for your child, I think it's kind of a good litmus test because the right practitioners are curious. They're wanting to understand what's now available. If you have a practitioner who's like,

I don't understand that and I'm not even gonna look at it. That's probably a good red flag that maybe your practitioner doesn't have the curiosity or isn't as open as perhaps might be a fit for what you're looking for. But that's at least the way I would interpret it.

Paniz Jasbi, PhD (36:35.138)

That's a very good litmus test and I would echo that as well. think physicians have a certain awareness of metabolomics. I think a lot of physicians who are venturing into this space don't have the self-confidence yet. So we do trainings, we do all of these things to sort of give them the fundamentals. The physicians that have the most, that are kind of leading the vanguard of metabolomics applications in clinical care, those are the oncologists, to be honest with you. Oncologists have been using this.

as a routine test in many of their practices, both private and hospital-based practices, for the last 10 years at least. So they've been a little bit ahead of the curve. And I think if your physician immediately dismisses metabolomics out of ignorance or maybe out of being the imposing sort of formidable nature of this new set of data, yeah, that's a good sort of red flag for you to maybe consider going somewhere else. I agree.

Len Arcuri (37:31.371)

Fantastic. Yeah, no, I'm excited. And again, I'm always curious, always open for these new tests. I think, and it can seem like it's overwhelming, but it's phenomenal that so many advances are being made. And I know, again, you're expending a lot of energy on making this a reality. Ultimately, it comes down for a parent. Can they get really good at revealing, what are the major root causes that are going on for their child right now that are

kind of holding their child back. And I think your report will help pinpoint those potential root causes in a very meaningful way. And again, I'm excited for you to be here, to be able to share what you're doing and the availability of this test. Would you like to kind of share with people where they would go for more information?

Paniz Jasbi, PhD (38:19.82)

Yeah, you can go to www.therio.me. That's T-H-E-R-I-O dot me. And there you can request an informational session with some of our clinical liaisons. You can view our guide to metabolomics, a very simple 20 page document with figures and really easy to follow logic.

You can also download a sample report, some of our case studies. And, you know, I think this is valuable. When I review some of these reports that are linked to individuals indicated to have ASD, what we typically see, you know, across the board are mitochondrial dysfunction, redox imbalance, oxidative stress, abnormal amino acids, neurotransmitter metabolism, folate and methylation pathways are off. And when we look at those...

Len Arcuri (39:12.973)

of us fully at least we can turn on the of the

Paniz Jasbi, PhD (39:16.002)

gut microbiome derived metabolites, they're off. And a lot of things that we actually see is, again, environmental and detoxification burden. So parents can go to the website and see how the report's structured and maybe gauge for themselves if it would be worthwhile to implement this with their child.

Len Arcuri (39:21.389)

again, if I can get some more feedback, I do some further research on the website.

Len Arcuri (39:31.767)

Fantastic. so you went to root causes and I would be curious, I know you may not have enough data, you don't specialize in working with children with autism per se, but if you just take a step out of your role right now and just looking at the data and knowing autism the way you do autism spectrum disorder, what would off the top of your head be what you would think are the more bigger root causes?

that are behind this epidemic. mitochondrial dysfunction being one as an example.

Paniz Jasbi, PhD (40:01.586)

I think the mitochondrial dysfunction is the number one, I think. And it's tied to symptomology very strongly, in our experience and in the data. So many children with autism show disrupted mitochondrial energy production. So in the reports, we will see altered Krebs cycle intermediates, specifically citrate, succinate, fumarate, malate, alpha-ketoglutarate. And what this is showing us is that

cells may not make energy efficiently. This is leading to downstream effects on brain development, immune activity, and of course, behavior. And I think this really dovetails again with the aerosol test because we measure these TCA cycle metabolites directly. That would be the number one thing I can pinpoint as a pattern, both in scientific literature broadly, as well as our own data that we have banked on individuals with and without ASD.

Len Arcuri (40:59.725)

All right, great. Well, Panisse, thank you so much for taking the time to shed light on this opportunity for parents. We're wishing you and your company and all the research you're doing, just wishing you great success at uncovering more and more ways of helping people, and in our case, particularly, parents on a journey to support their child. So thanks very much.

Paniz Jasbi, PhD (41:19.566)

Thanks for having me, Lin.

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