In his 2024 Wellness Academy Lecture, Sean H. Adams, PhD, discussed the complexity of our microbiota and its metabolites. He focused specifically on xenometabolomics, the study of foreign metabolites from microbes, and the metabolites developed in our microbiome.
During his insightful Q&A session, Professor Adams offers insights on probiotics, the gut-brain axis, and the future of metabolic research.
About the expert: Sean H. Adams, MS, PhD
Sean Adams, MS, PhD, FTOS, is a Professor and Vice Chair for Basic Research in the UC Davis Department of Surgery. He is also the founding Scientific Director of the Center for Alimentary and Metabolic Science, focusing on metabolic physiology, nutrition science, and gut microbial metabolites. During his career, he has been involved in research programs awarded over $130M, including $25M+ in NIH and USDA grants since joining UC Davis in 2020. Dr. Adams is an Associate Editor for Advances in Nutrition and a Fellow of the Obesity Society. His academic background includes degrees from Cal State Fresno, UC Santa Cruz, and the University of Illinois, followed by postdoctoral fellowships at the University of Barcelona and the UT Southwestern Medical Center in Dallas. He has also worked in R&D at Genentech, Novartis, and Amylin Pharmaceuticals, and recently founded XenoMet, a start-up focused on health products derived from natural metabolites produced by gut microbes and probiotics.
Q&A with Sean H. Adams, MS, PhD, FTOS
This transcript has been edited for clarity.
Q: Could you comment on the bacteria in our microbiomes and its interactions with pre and probiotics?
Dr. Adams: Yeah, it’s a question about what is a probiotic, what’s a prebiotic. And how does this interact with the gut microbiome and things of this nature.
So, a prebiotic just to start, that is anything that would promote the growth of healthy bacteria in your GI tract, which would be just the innate bacteria, for example, butyrate producers. Butyrate is a is a metabolite produced by some bacteria that is known to be very, very, health promoting for a variety of different reasons.
So, you might take a prebiotic like a type of fiber, for example, that would actually be a sort of food to promote the growth of that particular type of bacteria. So, it serves as a substrate from which they can grow and metabolize. So that’s a prebiotic.
A probiotic, of course, is, a live version of a health promoting bacterium and that could come in food or that could come in pills. I think many of us have taken probiotics in our life. And again, these are usually single species that are taken, but sometimes they can be a mixture of various species of bacteria. The issue with probiotics to editorialize a little bit is we often don’t know exactly how they’re working.
And so it’s a very generic term that’s often thrown around. You might have a physician or a friend tell you to take a probiotic because it’s going to make you healthier. But which probiotic and why? Why is this one different from this one? Well, we don’t know the full story of that.
That’s what we’re trying to do in our laboratory. Other people are trying to understand all the metabolites that these probiotics make that could link to health, to try to differentiate them from one another, or maybe even come up with new probiotics and new prebiotics that can promote metabolic outcomes that we find desirable.
Q: Will probiotics help facilitate these metabolic outcomes that you’re measuring in your labs?
Dr. Adams: Great, great, question. We were actually funded with a recent grant and we’re studying this in other ways as well to start to understand what probiotics are making. And there are other groups doing this. We’re not the only place on the planet doing this. But just knowing what these probiotics that we’re putting into our body are making a what they can make is critical because I think eventually what we’re going to find is certain probiotics will produce certain metabolites that are distinct for that class of probiotics or that species or whatever we want to call it, and we’ll know it. We’ll know what they’re making. And then we’ll be able potentially to say, okay, this probiotic is better for you. Person A but this probiotic better for you person B because of your particular condition.
Maybe it’s gut health you’re concerned about or cognition or whatever it may be. Once we begin to understand what the bioactive molecules are for each of these probiotics, we can even think about exploring new probiotics based on their metabolic patterns. That’s the future. That’s where everything’s headed and how you can distinguish one probiotic from another.
Q: So overall, what would be your recommendations for our audience who are asking questions about whether taking probiotics has any health benefit to what you’re seeing at this stage? Would it be correct to say that the foods don’t have as much influence as we were maybe previously thinking?
Dr. Adams: We have to remember certain foods do contain sort of fermented or bacterial products or even live bacteria. I didn’t mean in the earlier part of my talk to say those are not relevant or potentially healthy.
In fact, I think the epidemiological studies of some of the controlled trials do show that many of these foods have a health effect. So having those fermented products in there or these live bacteria can have a health effect. The question is how? How does taking this food with live bacteria colonize parts of your GI tract? How does that convey the health effect that people are seeing when you feed people that food? That’s the big mystery, in my opinion, except for a few metabolites, such as I said earlier, butyrate that’s a well-known one that many thousands of people have studied. But think about it, there’s 10 or 20 or more thousands of these metabolites in the blood.
We’re studying one, 2 or 3 of these only at this time. So, I don’t know if that answers your question, but yes, there are healthful components of foods that have been fermented or that contain probiotic bacteria. Absolutely. How they’re doing their work in the body is something that we’re studying, and other people are trying to study at the molecular level.
Q: Is this where you’re seeing the actual, connection or activity between the gut and various other structures in the body, the so-called gut brain axis, for example? Is the metabolome the mediator of this?
Dr. Adams: I think most people think so. I mean, I think there are other mediators. For example, some people are studying peptides, which are small little protein bits, or small strings of amino acids. There are other things, other bioactive components of these, coming from these bacteria. But I believe that the metabolites are the key.
So, for example, those indole metabolites I showed in the talk, those are now very well studied with well-known receptor system or systems that are anti-inflammatory and have other effects as well. And that’s a tryptophan metabolite. And so, a lot of people are trying to figure out how do we modify how the bacteria are metabolizing tryptophan, so that they can then increase the amount of these indels in this bioreactor, which then is thought to be anti-inflammatory.
So, people are thinking about these things. Same thing with butyrate. How can we give a particular type of fiber or probiotic that will promote the production of that short chain fatty acid, which is known to hit certain receptors and have a lot of really health promoting effects? So, people are already thinking about modifying the bacteria with their fiber content or whatever.
It’s just a matter of what the other thousands of metabolites are doing in terms of the gut brain axis. So, the gut is, other than the brain, really the most nerve dense part of our body. And so, the nerves are constantly interrogating the GI tract and the GI tissue. It’s something we don’t think about a lot, but the nerves that head north are interrogating all the time what’s happening in the GI tract and part of the way they sense things is through these metabolites. Some are well-known like serotonin and some others that people talk about. But my gosh, these neurons are bathed every day in these metabolites. And this must be impacting what the brain is, what the brain is doing with cognition, so on.
We don’t really know all those answers yet. As of today, my recommendation would be people look at the epidemiological evidence when it comes to certain foods and diet patterns and health, because if you look at different kinds of high fiber diets, for example, rich in fruits and vegetables, all of these things still hold true. Yogurt is shown to actually have some health promoting effects and so on. Fermented foods as well. You’ll get a diet pattern or certain foods which relate to health. That’s what we know today.
What we don’t know so much is once they get into the GI tract and they’re metabolized by the bacteria, what are those different foods and diet patterns promoting? That’s the next frontier, because that really gets to the molecular level of how those diet patterns are helping our health.
Q: Do you have any comment to make regarding the use of antibiotics? How do antibiotics interface with our so-called healthy bacteria or the gut microbiome that you’re studying?
Do we have any information about influence of antibiotics? Yeah, this isn’t exactly my area of expertise, and I’m not going to make any recommendations about if you should take antibiotics or not. Most of the time, obviously we need to take them for some reason or another.
Antibiotics can have a profound effect on the on the microbial communities that are there. That’s the bad news. And some of the good bacteria can start to kind of wane a little bit. That’s the bad news. The good news is typically most people rebound very strongly after they’ve taken a course of antibiotics. And you hear all the time, you know, some people will suggest taking more fermented foods and other things like this to sort of replenish that bacterial community in the gut.
Q: Do you have any recommendations along the lines of books or any recommendation that our audience can look at that would be useful for them?
Dr. Adams: Yeah. In terms of books that are specifically thinking about the Xenometabolome, I’m not aware of any. You’re prompting me to have to go look, because I’m not aware of anybody really going into that level of detail.
The thing I was going to put in the chat today was to have people look up the American Gut Project, which is now called the Microsetta Initiative, which I think is kind of a fun place for people to explore. This is a project that’s been going on for a while down in San Diego with different collaborators that’s trying to sort of map the microbiota of millions of people to understand how we differ from one another and how people change over time. There’s some talk of ‘what is a healthy microbiome?’ What does that mean? So, they’re doing some interesting work in this regard. So that’s my recommendation. I was going to tell people to go look that up. The Microsetta Initiative, which very interesting.
You can watch Dr. Adam’s full Wellness Academy lecture here.
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