Why Bone Loss Accelerates With Aging: The Gut–Bone Connection

I just had a really fascinating conversation with Mark Charbonneau and Alicia Ballok, the scientists at Sōlaria biō, about a line of research that genuinely made me stop and rethink how we approach bone health. We talked about their journey from isolating microbes living inside edible plants, to identifying synergistic microbial interactions, to building out the preclinical work and then taking it all the way into human clinical research. It’s a rare and thoughtful progression, and the science is compelling.

Their first clinical focus has been bone loss, and the results they’ve seen so far are striking. In an early clinical study, they reported a substantial reduction in bone loss, up to 80% in certain groups, along with meaningful reductions in CTX, one of the key markers used to assess bone turnover. They’re now recruiting for a follow-up study in postmenopausal women in collaboration with Harvard, and we’ll share details in the show notes for anyone who may be eligible. This is a rich, science-forward conversation, and I think you’ll find it as interesting as I did. ~DrKF

Bone loss doesn’t start when fractures happen; it starts years earlier.

In this episode, we explore why bone aging accelerates with menopause and how the gut microbiome may be a hidden driver of skeletal decline. Dr. Kara Fitzgerald speaks with research scientists from Sōlaria biō, the company behind Bōndia, about their work studying plant-based microbes, designing microbial “synergies,” and uncovering new links between gut health, inflammation, and bone loss in peri- and postmenopausal women.

We break down findings from a randomized, placebo-controlled clinical trial published in the journal Osteoporosis International examining a microbiome-based intervention for bone health, and discuss why bone loss needs to be addressed earlier, systemically, and beyond hormones alone.

In this episode of New Frontiers, learn about:

Dr. Kara Fitzgerald: Hi everybody, welcome to New Frontiers in Functional Medicine where we are interviewing the best minds in functional medicine. And of course, today is no exception. In this episode I am joined by Dr. Alicia Ballok and Dr. Mark Charbonneau. These are two research scientists who are doing incredibly thoughtful, cutting-edge work in the microbiome space. Alicia is a microbiologist and immunologist by training. She’s currently the director of discovery at Sōlaria biō where she’s helping lead the development of novel plant derived synbiotics for inflammatory and immune mediated conditions. Mark is a systems biologist whose research has focused on how early-life gut microbiota shape growth and health outcomes. He trained in Jeffrey Gordon’s lab at Washington University and brings over a decade of experience in microbiome research and live biotherapeutics. He’s now helping to shape innovation at Sōlaria.

Dr. Kara Fitzgerald: Their first offering is something called Bōndia, specific to bone health. They’re showing it as a potent anti-inflammatory, and in dropping inflammation, it’s preserving bone health. And they’ve shown significant drops in the classic measurement of bone loss, CTX, and just on and on. So take a listen to this podcast. I think you’ll really find it just exciting, interesting, mind blown moments.

Dr. Kara Fitzgerald: Mark and Alicia, it’s just great to have you both here with me on New Frontiers. I just want to give a micro backstory of my experience with Sōlaria biō. I’ve known Lisa McDonald, who’s a part of your team, for many years and she pinged me about this very exciting company who was up to some really interesting science. Of course, that’s going to perk my ears up and it’s going to perk the ears of people who are listening. And she started to just lay out who you are, and your preclinical work, and your pathway to discovery, and the clinical work. And I don’t want to go into what it is because I want you to tell the story, but let me just say, I was excited. I invited you to come dialogue with my clinical team at rounds. My clinical team was excited. You were on our Masterclass and the masterclass folks [attendees] were interested. And so here we are to do a little bit longer drill down into who you are and what you’re up to. And we’re going to start with the origin story. So go ahead and dive in, Mark. Tell us about who Sōlaria biō is and how you got to thinking about fruits and vegetables.

Mark Charbonneau, PhD: Well, first, let me say thank you for having us. It’s really a pleasure to talk to you and it’s always a pleasure to connect with your community. Everyone there is so engaged and we really love that and so it’s a pleasure to be here and talk to them again. So, I’m Mark Charbonneau, Vice President of Research at Sōlaria biō. Sōlaria has been around for about eight years now and the company started with a pretty simple idea, which is that we spend quite a lot of time and energy in the scientific community thinking about what is the diversity of the microbial world in some of these really far-flung places like hydrothermal vents in the ocean or is there life on Mars? But we’re not necessarily asking the question about what’s living right in the foods that we’re eating every day, or in the farmers market that we go to on the weekend.

Mark Charbonneau, PhD: And what I was really surprised to learn when I joined Sōlaria is that the amount of microbes that live inside of fresh fruits and vegetables, the kinds of healthy foods that we should be eating every day is profound. If you eat a salad, you’re really consuming about the same amount of bacteria as you would get in a probiotic supplement that you might buy at the store. And so the central hypothesis that Sōlaria was founded on is this idea that those foods are good for us. We know that, but the microbes in them may be a major component of all the benefits that we get from these fresh fruits and vegetables.

Mark Charbonneau, PhD: And so the company was founded on that idea and since then, we’ve spent several years isolating thousands and thousands of organisms from both bacteria and yeast from these foods, building a large library and a platform that we can use to then recombine those organisms based on those beneficial functions into new solutions for some of the pressing health challenges that we face as a community.

Dr. Kara Fitzgerald: I want to back up just a second. That’s all really interesting but I just want to make sure that the listeners heard that we’re talking about microbes within the food. I mean, when I was first introduced to you I just assumed you were harvesting these microbes from the skin, from the outside, you know, that it was resident flora existing there. But basically, what you’re suggesting Mark, is there’s a heck of a lot going on inside. I know we’re going to drill down into that more, but would you say if you’re eating a good salad, as I almost always have here in my bag for lunch, what I’m basically eating is a probiotic food, even though I don’t necessarily have my added kimchi?

Mark Charbonneau, PhD: Yeah, that’s right. Well kimchi would have even more, but I think that’s a good characterization. I’ll let Alicia dig into that a little bit.

Alicia Ballok, PhD: Yes.

Dr. Kara Fitzgerald: Talk to me, yeah, Alicia, just go ahead. You’re going to talk about the microbes that come internally from the plants, the internal microbiome of the plants and you turn these endophytes– Go ahead and take us through.

Alicia Ballok, PhD: Yeah, so when we’re thinking about microbiomes, oftentimes we’re thinking about a human microbiome or the microbiome of our dogs. But actually the plants we eat have microbiomes as well and those microbes that live within those plants are called endophytes. And they’re not just on the surface, they’re in the tissues and they’re actually providing beneficial chemicals to the plants to help them grow better, to survive stress better. And some of those chemicals are actually beneficial for ourselves as well. And so we’ve amassed a library of over 5,700 microbes from these healthy foods to help us to develop products to tap that biology and improve our own biology.

Dr. Kara Fitzgerald: So basically, they’re creating these chemicals. So, they’re metabolizing the food—let’s just take an apple—the internal microbiome is consuming the apple, not dissimilar from if we eat an apple, our internal microbiome is going to start breaking it down. And they’re basically producing post-biotic compounds, which are these chemicals that are healthful for us. Is that a correct characterization, Alicia?

Alicia Ballok, PhD: Yes, that’s absolutely correct. They can be helpful for the plants that they’re residing in and helpful for us. We’re actually almost using the plant itself as a pre-selection tool for us to generate these new products.

Dr. Kara Fitzgerald: It’s so cool. We think about our phytochemicals, the polyphenols, I mean, we’re obsessed with those in functional medicine. But there’s probably a massive suite of these postbiotic compounds that have been acted on by the internal microbiome of the various fruits and vegetables. And your team has just done the drill down into exploring these. So thinking about this internal microbiome of plants, the endophytes as they’re referred to, what’s the significance of the functions encoded by the microbiome and how do they relate to therapeutic potential?

Alicia Ballok, PhD: So actually, these microbes are able to produce a number of different functional molecules. These can include short-chain fatty acids that we’re probably familiar with because our own microbes and our microbiome are making those, as well as products like indole derivatives that have important signaling for immune cell regulation, and polysaccharides that can have immunomodulatory potential as well. These are just some of the many molecules that these microbes are producing that have an impact on how our bodies respond to our environments and inflammatory response.

Dr. Kara Fitzgerald: That’s so interesting to me. So again, we’re going back to this apple, or maybe this lime that I’m going to squeeze into my water in a minute, and it’s got some butyrate in there, potentially. Could it?

Alicia Ballok, PhD: They have butyrate producers, yeah.

Dr. Kara Fitzgerald: That’s so wild. That’s very interesting. Okay, so Mark, you’ve isolated thousands of these compounds from plants. How do you move towards determining the players that you want to work with for therapeutic solutions?

Mark Charbonneau, PhD: I think this is really the core challenge of what we’re looking at, because as you mentioned, we have thousands of organisms, both bacteria and yeast, that can encode many different beneficial functions. But if what we’re looking to do is develop a new health solution that is a combination of three, four, five of them, how do you pick? Because the number of potential combinations is hundreds of millions, even billions of combinations. There’s no way we could test them all. And so what we’ve done is to build a computational platform that lets us predict how these individual strains function by sequencing their genomes, annotating those, and then predicting what are the functions that they encode and doing that in a data-driven way.

Mark Charbonneau, PhD: And then beyond that, developing similar models that allow us to predict how they will work together. When you put the two organisms together, will they benefit one another? Will they compete with one another? And at the end of the day, how does that relate to the function of the final product? And for Sōlaria, what we’re most interested in are functional synergies where you don’t just have one plus one equals two, you have one plus one equals three. Or the function of some of the organisms can amplify the others through various different mechanisms to give you more bang for the buck.

Dr. Kara Fitzgerald: Really interesting. Alicia, how did you guys figure that out? How do you define synergy and how are you designing based on that?

Alicia Ballok, PhD: Yeah. As I mentioned, there are those important metabolites that we’re looking for. And Mark just said, we’re looking for the one plus one equals three. You know, organism A is producing X amount of a short-chain fatty acid, organism B is producing Y amount, but when they come together, they’re producing four or five times that amount. And so that means that they have a positive interrelationship, which is actually really rare in probiotics and microorganisms in general. We’ve done studies ourselves where we’ve looked at organismal interactions and we found on average about 14% of them are positive, beneficial interactions and the rest are negative. So that’s something to keep in mind.

Dr. Kara Fitzgerald: You mean negative in that they’re damaging or they’re just non-existent or…

Alicia Ballok, PhD: They can be slightly antagonistic. So like one organism might out-compete another organism so they’re using up the food source they need to make the things that we want. Or when they interact, they’re antagonizing the production of that molecule that we care about. And we see that more often than not and so we are looking specifically for instances where they can work together to improve and enhance those products and those interactions.

Dr. Kara Fitzgerald: I just want to make sure everybody’s clear. When you reference that sort of an antagonistic interaction and only a 14% beneficial synergy, you’re speaking about probiotics, probiotic formula design. Is that correct?

Alicia Ballok, PhD: Yeah. When we’re looking at probiotic organisms together in laboratory settings, we’re seeing this. So that is a consideration when thinking about probiotics that you’re purchasing. If you’re getting a product, even if it says it has 100 billion CFUs or 10 billion plus CFUs, if it’s a laundry list of organisms and there hasn’t been any thought put into that design of that product, and they’re just like, well, these are all beneficial organisms, most of the time, those organisms are not going to be friendly with one another and give you those things that you’re hoping to get from them. We’re specifically designing our products around beneficial interactions so that we don’t lose any of those beneficial properties of the individual organisms. And hopefully, we see complementarity.

Dr. Kara Fitzgerald: Yeah, I mean, again, it’s a really obvious question. And it makes sense. Even though they’re good guys, the collection of probiotics in a given formula, do they play well in the sandbox? Maybe they do, maybe they don’t. And there’s all sorts of variables. It’s very interesting that you’re studying it. We had a really cool conversation a while ago with Nathan Price who was at the Institute for Systems Biology and he was talking about a digital twin. Is that kind of what you’re doing there with the AI? I’m just curious to try to gauge what’s happening.

Mark Charbonneau, PhD: So what we’re doing, I think, is a little bit unique in the sense that traditionally, the way that this problem has been approached, the problem being how do you predict what probiotics are going to do, is you take a look at the genome of the organism, you predict where the genes are, and compare that to work that’s been done experimentally in the lab over the past 70 years and published in the literature. And that’s great for cases where we have experimental data that tell us what the genes do. But very often we don’t have that information. So particularly when you consider that most of the organisms that we’ve isolated from fresh fruits and vegetables are new. They haven’t been described before so how do we know what they do?

Mark Charbonneau, PhD: The approach that we’ve taken is a bit more data driven, where we are allowing the computational models to learn from the data itself. We give it examples of, okay, here are 10 strains, or 50 strains that we’ve characterized in the lab, and this is what they do. The model can then learn from that how the genes connect with those functions and essentially pick up on signals that we humans don’t know. And in doing so, we can actually get greater accuracy than just looking at the genomes ourselves in the old-fashioned way.

Dr. Kara Fitzgerald: Well, and then you moved into the clinical arena, and we’re going to get into that, but I just have one more geeky question I can’t help but ask. Again, we’re thinking about phytochemicals all the time, we’re thinking about polyphenols, and postbiotic compounds and the body of research is accumulating in that arena. And we can see some postbiotic compounds are exquisitely powerful, just extraordinarily powerful. Could there be in the future a place where you’re actually looking at some of these plant-based postbiotics and harvesting them and they could have therapeutic potential?

Mark Charbonneau, PhD: Yes, absolutely. I think there’s couple of dimensions to that. I think there’s the function of the compounds themselves that are in foods. I think the other consideration is, if we’re talking about fresh produce where you have billions of microorganisms inside of them, how are those microorganisms transforming the food and actually adding to its milieu of beneficial compounds?

Dr. Kara Fitzgerald: Yeah, super curious. I could just go down such a rabbit hole there and what’s the difference between organic and not organic? Because I know the listeners are thinking those similar questions.

Mark Charbonneau, PhD: Incidentally, we have observed that organic produce tends to have higher diversity and abundance of probiotics in it than conventionally farmed. But what impact that has, I think, remains to be determined.

Dr. Kara Fitzgerald: Okay, so let’s get to where the rubber meets the road and talk about clinical application now, you know, how you’re bringing this to us. We’re using your initial product in my clinic, actually. We’ve been pretty excited about it. So your first foray has been into bone health, especially in women, peri- and postmenopause, when we really see it kick in. Talk about this whole journey, how rapid bone loss is happening. That’s over to Mark, and then we want to think a little bit about bringing this to use in this population. So go ahead, Mark, and give us some background.

Mark Charbonneau, PhD: So just to step back and try to frame the problem that we’re looking at, it really pertains to bone health and what we see as essentially a silent crisis that’s happening all around us with people’s bones. What happens is that we reach peak bone mass sometime in our early to mid 30s. Of course, when we’re in adolescence, it goes up, we get all our bones, and then what we have in early adulthood is what we have. And then after that point where we reach the peak, we typically have gradual year-over-year decline in bone mass until there’s an issue for the remainder of our lives.

Mark Charbonneau, PhD: That happens for everybody, but in women, it tends to be exacerbated by the menopause transition. And there are a variety of reasons for that, but really a major one is a decrease in estrogen production that can have both direct and indirect effects on cells of the bone. I’m sure your listeners know this, but bone is not a static thing. It’s not like concrete. It’s a living tissue just like any other that’s constantly being rebuilt with this balance of processes of buildup and breakdown. And what happens as the estrogen levels go down, inflammation increases and the rate of bone breakdown exceeds the rate of bone buildup. And so over time you have bone loss and during menopause that’s accelerated substantially.

Mark Charbonneau, PhD: And so then what you end up having by the time women are in their 50s to 60s, bone mass has dropped to such a level that the risk of fracture is substantially high. Currently, clinical guidelines indicate that we give most women DEXA scans to look at their bone mass sometime in their mid 60s. And essentially, that’s too late because by that point 80% of women already have either low bone mass which is called osteopenia, or they have osteoporosis and it’s time to act. So really we’re looking for solutions earlier on. How can we maintain that bone when people are younger, stop those inflammatory processes and keep that bone mass as high as possible.

Dr. Kara Fitzgerald: Yeah, right. So just thinking about the problem of osteoporosis, you know, and us dialoguing on it, and I brought it to our rounds, actually. So we had our physicians rounds right after our conversation and it was really top of mind, the fact that bone loss is kicking in way sooner than we look for it. And you found that actually as you were recruiting for a study, so maybe you can mention that. I’m curious about it. But also men, I mean, we see it. During our physicians rounds I was talking about a patient of mine who’s not even 30 yet and he got a DEXA to look at body composition and, oh hey, by the way, you’re osteopenic.

Dr. Kara Fitzgerald: What’s going on at 26? Why is he osteopenic? And malabsorption, gut issues, all sorts of things, but we haven’t found sort of an obvious smoking gun, but we can put together collections of imbalance that prompted very early onset bone loss in him. I just think this is a much, much greater problem in men and women than we’ve appreciated. And to your point, Mark, we need to start screening way, way, way sooner and doing the preventative interventions.

Mark Charbonneau, PhD: One of the things I think in response to what you just said is that we’re not thinking about bone loss early on. And I think that’s for a couple of reasons. One of them is that it’s silent and asymptomatic, that you don’t feel your bones losing density until there’s a fracture and at that point, the impacts are tremendous. If you look at hip fractures, for example, only 40% to 60% of people who experience a hip fracture will ever recover full mobility that they had before that. And even more alarmingly, there’s about a 22% all-cause mortality that follows a hip fracture in the first year. So while people are not necessarily dying because of the hip fracture directly, there are many other complications and costs that come with that and we’re just not looking at these things early.

Mark Charbonneau, PhD: From my perspective, the other main issue is that we often think about this just through the lens of osteoporosis. If I have osteoporosis, I have a problem. If I don’t have osteoporosis, I don’t have a problem. And that is simply not the case. People who have osteopenia, again, which is low bone mass, that’s not yet in the category of osteoporosis, have a lifetime fracture risk of over 40%. So that’s almost as high as if you have osteoporosis, but we’re often not thinking about it that way.

Dr. Kara Fitzgerald: And arguably, as we were dialoguing in our physician’s rounds yesterday, we just need to be screening. We need to be more aggressive and earlier about screening. And you’re going to talk about your data on CTX and I just want to say that’s a pretty easy measure. We can get it from Quest and we can get an idea in any of our patients in practice, even my 20-something-year-old, otherwise healthy male. And by the way, he happened to have an extremely high CTX that you would never think about in somebody who’s not even 30 and male. And now it’s down. He’s successfully engaged in diet and lifestyle changes, including Bōndia, and it’s down. It’s fabulous. It’s in the 200s where we would want to see it.

Dr. Kara Fitzgerald: All right, so with that in mind, let’s talk a little bit about the gut-bone connection. Alicia, do you want to talk about why you guys figured out or why microbes could possibly be a piece of the solution here?

Alicia Ballok, PhD: I think a lot of people are aware of how our gut is actually a kind of important immune mediator. The reality is about 70% of our immune cells are gut-associated and that’s for a reason. The gut is a big driver of immunity, inflammation, and so forth, so it makes sense that it’s a mediator. In fact, when we’re looking at mouse studies as an example, you can induce a menopause-type state by removing the ovaries from a mouse, it’s called an oophorectomy in that system, and they’ll lose bone. But if you eliminate the gut microbiome, you have these germ-free mice, and you do the same surgery, you remove those ovaries, you actually don’t see bone loss. So we know that there is a connection there.

Dr. Kara Fitzgerald: Interesting.

Alicia Ballok, PhD: And the question is how to tap that? How do we impact that? And so what we thought we would address first is some of those things that we know are important drivers of inflammation and immunity within our gut. So again, going back to those short-chain fatty acids, we thought that would be a great target for development of a bone health product. Additionally, microbes can produce vitamin K2, which we know is important for calcium metabolism, and other potential anti-inflammatory molecules. These all coalesced into the development of Bōndia, which really has a strong impact on synergistic production of short-chain fatty acids, production of vitamin K2, as well as other anti-inflammatory compounds, even neurotransmitters.

Dr. Kara Fitzgerald: Super interesting. I want to just circle back to what you said because what you suggested in the animal models was very powerful. We know as estrogen drops, bone loss increases in humans. That’s really well established. So estrogen has this bone protective kind of anti-inflammatory effect. When we look in mice who’ve undergone oophorectomy, same thing. Bone loss happens when you pull out access to estrogen. However, when you layer in a sterile gut, you pull out the influence of the microbiome in the mouse model, you stop bone loss. So you’re really suggesting here that yes, bone loss is estrogen-mediated, but there’s this profound driver of inflammation. And if we could control the inflammation, maybe with or without HRT, of course, you’re aware that we’re using HRT, thank God, more liberally these days, and bone loss patients are really good candidates for it. But a potent, potent driver, perhaps greater, is the inflammation driven by an imbalanced gut.

Alicia Ballok, PhD: Yeah. I don’t know if lots of people are thinking about this, but osteoclastogenesis, the development of those bone-breaking-down cells, is actually an inflammatory process. It uses the same inflammatory signals that drive maturation of macrophages.

Dr. Kara Fitzgerald: Yeah. Very interesting. It’s just important to think, as we’re doing in functional medicine, through that system’s lens. So you decided to pull those together and create the Bōndia product. I think we’ve made a really good argument here over the course of this podcast so far to eat your fruits and veg. They’re loaded with their probiotics. They’re basically pro- and postbiotic foods. You’re eating just a massive rainbow of a microbiome, if you will, in these postbiotic products and we need to continue to do that in a healthful way. But you wouldn’t necessarily see the benefits that you’re seeing in Bōndia and we are going to get to the research. So speak to that Alicia.

Alicia Ballok, PhD: Sure. So yes, these are naturally derived. All of the microbes that come from Bōndia are either isolated from squash or fermented pepper paste. But to get the same dose of microbes that you get from the squash and the fermented pepper paste, you’d have to consume 1.2 pounds of fermented pepper paste and three and a half tons of squash. So those beneficial microbes are there, but they’re not necessarily there in the quantities we need in our bodies to affect that change. So unless you’re the best competitive eater, I don’t think you stand a chance.

Dr. Kara Fitzgerald: Yeah, right. I can’t even imagine that many tons of squash, what that would look like. So you put together this really cool product—obviously folks, papers, links to Bōndia, and what it is, will be on the show notes— and you started to investigate whether or not the hypothesis is going to bear out in human models. So talk about that Mark.

Mark Charbonneau, PhD: Yeah, of course. As Alicia mentioned, we were really interested in developing a product that could synergistically produce these anti-inflammatory compounds. And the product of that process is our synbiotic medical food that’s called Bōndia. Bōndia is a synbiotic, so it has both pre- and probiotics in it. The probiotics are four unique strains that are all derived from fresh fruits and vegetables. They include three bacterial strains and one yeast strain, in addition to two prebiotics, oligofructose and an organic blueberry powder. And those prebiotics function as fuel for the microbes so that they can make those anti-inflammatory compounds in the gut.

Mark Charbonneau, PhD: In addition to that, we also formulate Bōndia with the recommended daily allowance of vitamin D just to ensure that’s met as well. And so for us, what really matters is not just that we put this together, but that we demonstrate convincingly in a clinical setting that an intervention like this has a real clinical benefit for individuals who are losing bone. We just completed a randomized placebo-controlled study where we enrolled 286 women who were all in the early stages of menopause, so between one and five years post-menopause, all of whom were not osteoporotic. They had osteopenia or healthy bone, but they were in that period of life where we expect very rapid bone loss to happen.

Mark Charbonneau, PhD: We then randomized these individuals to either receive Bōndia twice a day for one year, or a placebo, which in this case was just vitamin D and the fiber for one year. The objective was to then look at how would bone loss differ between these two groups as measured by DEXA scans at 0 and 12 months. And we’re also looking at not just everybody, but particular groups of individuals where they’re more at risk for bone loss, including people with osteopenia, which indicates that they’re already already losing bone.

Dr. Kara Fitzgerald: And what did you find?

Mark Charbonneau, PhD: What we found was really exciting and some of it was kind of surprising. We found that there were groups of individuals who had really strong benefits associated with taking Bōndia. Specifically, what we found is up to 85% reduction in bone loss for some of these groups. In the case of women with osteopenia, we saw an 85% reduction in bone loss at the hip. Similarly, in women with BMI of over 30, these are clinically meeting the criterion for obesity, in those individuals, we saw about a 75% reduction in bone loss in the hip.

Mark Charbonneau, PhD: And beyond that, because just as nerds we were looking at the data and thinking to ourselves, well, BMI doesn’t tell the whole story. Because really what we know here is that the connection between the gut and the bone is inflammation and we know that BMI is just based on weight. But in reality, because we have DEXA scans, we can look at the body composition for these individuals and we know that fat mass is very pro-inflammatory and can drive these processes. So when we looked at the body composition of the individuals in our study, one of the things that we found is that two thirds of the women who had elevated body fat, in this case, meaning 40% or greater, two thirds of those individuals, they were not obese. They did not meet the clinical criterion for obesity.

Mark Charbonneau, PhD: In other words, there was a big group of individuals in the study who had all of this pro-inflammatory tissue that may be impacting their bone. And consistent with that, when we looked at the effect of Bōndia, we found that bone loss in the hip was reduced by about 60% for individuals with high body fat, regardless of their BMI. So all of this together, we believe, is consistent with the hypothesis that greater inflammation leads to greater bone loss and that by introducing this anti-inflammatory intervention in the gut, we can reduce those processes.

Mark Charbonneau, PhD: One last thing I’ll note is that we also looked at biomarkers of bone turnover in the blood. One of the most important ones is called CTX. This is a marker of bone breakdown that’s made by osteoclast cells. They’re the cells that break things down. It gets released into the blood and we can measure it. One of the things that we found is that individuals who responded well to Bōndia, including those with elevated BMI, had significantly reduced CTX at 12 months compared to individuals on the placebo, which is consistent with not only reduced bone loss, but that the bones are being broken down more slowly as a function of taking that product.

Dr. Kara Fitzgerald: Right. Awesome. That’s just really exciting. I mean, when you started unpacking some of your findings, were you pretty excited? Were you like, wow, we’ve done something here?

Mark Charbonneau, PhD: Yeah, naturally it was really exciting to see such a profound benefit and in particular, because when we think about bone loss, it’s not a one year kind of thing. It happens progressively throughout our lives. We lose bone year over year and so the real benefit is if you think about it cumulatively. If you’re saving 80% of your bone in a span of five years, you could stop four years worth of that bone loss. So that’s where the real benefit can come in. Beyond that, of course we’re interested in the safety and the profile of how well tolerated the product is, because if you’re going to be taking this every day, it needs to fit into your life and be good for you.

Mark Charbonneau, PhD: We found that, consistent with prior studies we’ve done, that in this randomized clinical trial, Bōndia had an excellent safety profile. We saw no difference in adverse events or side effects between the placebo and the Bōndia group. But beyond that, we found something that was really interesting. We did what are called gastrointestinal tolerability surveys for everyone in the study throughout the entire study. And really what this is, is a survey of 12 questions, such as how are you feeling and what symptoms do you have? And one of things that we found is that the number of people who were reporting severe gastrointestinal symptoms, things like constipation and nausea, was reduced by about two thirds in the Bōndia group compared to the placebo group.

Mark Charbonneau, PhD: And the number of symptoms reported by those individuals was reduced by about 80%. So that tells us that while the long-term benefit of an anti-inflammatory product like this is to preserve the bone and really to maintain that independence and quality of life in the long run, in the short term, people actually felt better on it too, so it could have gut health benefits in the short term for those individuals.

Dr. Kara Fitzgerald: So it’s acting like a classic probiotic as well, interestingly enough, even though these aren’t microbes that reside in the gut and they don’t actually colonize but they stick around for a while. Isn’t that true?

Alicia Ballok, PhD: Yeah, that’s correct. We’ve actually ran a clinical study looking at how long Bōndia persists in the body after you stop taking it and it’s actually only about a week and that actually speaks to the safety. You don’t necessarily want to be colonized with your probiotic long-term because if something were to go wrong, that could lead to infection. So you really do want your probiotic to wash out within a safe timeframe. That study was also really interesting because what we found was that our microbes were detected early. So we looked at two days after somebody started taking the probiotic and we could detect it at high levels within their samples. Furthermore, when we looked for whether or not those organisms were alive by plating them, standard microbiological methods, we found that they were in fact alive. So we know that they’re in the body rapidly after you take it, they’re alive, they’re actively metabolizing and giving you those benefits that we were hoping for.

Dr. Kara Fitzgerald: Awesome. So they make it through to the specimen. I’m assuming these are fecal specimens and they make it through alive.

Alicia Ballok, PhD: I was trying to not say the word.

Dr. Kara Fitzgerald: I mean, most everybody here has probably either done a stool test or they’ve ordered a lot of them on patients. Any other markers or compounds that you looked at in the population beyond CTX that are worth mentioning?

Mark Charbonneau, PhD: Just for the sake of completeness, it’s worth mentioning another one called P1NP. That’s a marker of osteoblast activity. There are two primary cell types in the bone that we’re interested in here. Osteoblasts that build up bone and osteoclasts that break it down. CTX is the marker of bone breakdown. P1NP is the marker of bone buildup. We didn’t see any significant differences in P1NP, which tells us that the way that Bōndia is working is by turning down the bone breakdown rather than turning up building, which is important for us in terms of how we think about how it fits into clinical paradigms and management of patients.

Dr. Kara Fitzgerald: Yeah, and why don’t we talk about that? I have two questions. How do we use Bōndia in practice? Are we prescribing it alongside other classic therapies like bisphosphonates? Are we using it concurrently with HRT in the perimenopause/menopausal population? And also, beyond that? We were talking earlier about my 26-year-old male patient. Who is Bōndia indicated for and when would be the ideal start time? So there’s a bunch of questions I’ve thrown out to you. Using it concurrently and then also, who’s the ideal patient and when might we consider starting?

Mark Charbonneau, PhD: Yeah, absolutely. As you mentioned, the study that we designed was in postmenopausal women, but you can imagine it being relevant for perimenopausal women who are also in that period of rapid bone loss. As we think about where it fits into the clinical paradigm, we think about Bōndia as an early intervention to help preserve bone mass that you have when you’re young and keep that as long as possible. That’s the ideal.

Mark Charbonneau, PhD: For people who are maybe farther along in their journey and they are availing themselves of other options like bisphosphonates, we see Bōndia as compatible with that. There’s no reason to believe that bisphosphonates and Bōndia would be competitive with one another. They work by different mechanisms. And if you think about bisphosphonates in particular, one of the key issues with them is the longer individuals are on drugs like bisphosphonates, the higher the risk of atypical fractures becomes. So those individuals typically want to go off the drugs for some period of time, whether or not you like this term, taking a drug holiday, and Bōndia could be an opportunity to help preserve the bone that is built up by those drugs during that period of time. So that’s one option.

Mark Charbonneau, PhD: You also brought up hormone therapy, which thankfully is becoming more broadly accepted and used, and it’s very efficacious in many ways. One of the considerations is that the efficacious concentration used of estrogen or other hormones for hormone replacement therapy that is useful for things like vasomotor symptoms may not be fully efficacious for bone. And so there still is room to have as an adjunct or a complimentary approach, something like Bōndia that can help meet that other anti-inflammatory need and preserve that bone as much as possible.

Alicia Ballok, PhD: Actually, to kind of add on to that and address your young male example, when we looked at how Bōndia functions— So my team essentially did in vitro mechanistic exploration of this and what we found is that Bōndia works via improving the gastrointestinal barrier, reducing immune cell signaling, so certain specific cytokines such as IL-23 that is directly relevant to bone, and so forth, are reduced when Bōndia is taken in. Then we also see direct effects on osteoclast activity. These are all non-hormonal effects, so this could be beneficial for any individual who is experiencing bone loss, not necessarily just individuals who are experiencing bone loss as a result of loss of estrogen.

Dr. Kara Fitzgerald: One hundred percent. People are listening and thinking, well, I could use this in some of my tough gut patients because this mechanism is beyond preserving bone health. It’s anti-inflammatory via multiple mechanisms, although top of mind, just given your focus is on bone loss, and for me, again, as a clinician addressing it earlier, measuring it earlier, measuring it more frequently in the male population. This is something super safe. It’s well tolerated and it seems to me like it’s a real net benefit. What’s the research arena like now for Bōndia? What do you guys have in the pipeline?

Mark Charbonneau, PhD: Yeah, so we’re really interested in other populations where Bōndia could have an effect or a benefit for preserving bone. And there are several of them, but one of the ones that’s most important in our view is women who are farther along, and maybe are many years past menopause. We actually have another clinical study ongoing now, it’s in collaboration with researchers from the Marcus Institute of Aging associated with Harvard. And in this study, we are enrolling women who are age 65 and up, and that includes individuals who have osteoporosis if they are, of their own decision, not pursuing other therapeutic options. Hopefully, what this will tell us is that the benefit is there for individuals, not just in the period immediately following menopause, but throughout life. That study is actively enrolling now, and we’re really excited to see how that shapes up in the coming years.

Dr. Kara Fitzgerald: How long will it run for?

Mark Charbonneau, PhD: (44:35) We are monitoring those individuals for 18 months, so we’re probably looking at a couple of years before we would start having the early readouts. But I think that’s going to be a very important piece of information for us to fully understand how the product works and for whom it can benefit.

Alicia Ballok, PhD: And we’re still recruiting for that study, so if anyone wants to participate.

Mark Charbonneau, PhD: You do have to live in the Boston area or at least be willing to drive to Roxbury.

Dr. Kara Fitzgerald: Awesome. You have to live in Boston.

Alicia Ballok, PhD: Yes.

Dr. Kara Fitzgerald: Okay, perfect. Well, yeah, again, we’ll put that in the show notes. Anything you want to add on this, just thinking about Bōndia and bone loss disorders before we just more broadly speak about where you might be headed with this discovery?

Mark Charbonneau, PhD: I would say just generally, one of things that’s very important to us is to raise awareness of bone health, and that this is, like I mentioned, it’s silent and asymptomatic. When we were enrolling for our randomized study, we ultimately had 286 women, and 15% of the women that we screened that made it through all the other checks, at their baseline they got their DEXA scan and they already had osteoporosis and they had no idea. They believed they were otherwise completely good to go and we unfortunately had to tell them, you have osteoporosis. This is something to talk to your doctor about. So people are just not aware that it’s such an issue or or the potential risks associated with it if we don’t manage it early.

Alicia Ballok, PhD: These were women within one to six years postmenopause. So these are younger women, not anywhere close to 65 when we’re supposed to start running DEXA scans.

Dr. Kara Fitzgerald: Yeah. Lots of lessons here, I think, for us, just screening way, way, sooner and getting in there and being active. You have found out something I think is wildly interesting, that you’re unpacking the plant microbiome and the postbiotic compounds that are produced by this said microbiome and now you’re piecing together this potent anti-inflammatory effect and the benefits to the gastrointestinal lining and beyond, and to the microbiome in general. What’s next? Might you use this fundamental finding for other indications, maybe tweaking the formula? What are you guys thinking about?

Alicia Ballok, PhD: Yeah, we are looking at other indications. Not necessarily with the same formulation as Bōndia, but you can imagine that if we’re able to manipulate systemic inflammation through the gut, that there are a host of diseases. They can be autoimmune or generally inflammaging-related that we can modulate, and so that’s where we’re looking to go next.

Dr. Kara Fitzgerald: That’s very exciting and I want to just say, hats off to you guys for going through the steps to getting it FDA approved as a medical food. I know that takes some some energy and doing.

Mark Charbonneau, PhD: Yeah, that level of demonstrating the clinical benefit for us is something that’s really critical. Many supplements don’t necessarily have the same level of evidence, but we want people to be confident in what they’re putting in their bodies. But taking it back to the very beginning with what we were trying to do at Sōlaria with the edible plant microbes, the bone health solution is valuable in and of itself, but we see this also as a proof of concept that we can take beneficial microbes from fresh fruits and vegetables that have anti-inflammatory properties, recombine them into these synergistic combinations and demonstrate a benefit in humans. And as Alicia mentioned, we want to keep that flywheel going, move that forward and identify other opportunities to really have a big impact.

Dr. Kara Fitzgerald: Well, thanks for meeting with me today and just going through some of the science. How exciting it is. That’s all the questions I have. Well, actually, let me ask you this because I do have a question. You looked at osteoclast and osteoblast activity. Did you guys look at CRP, IL-6? You looked at inflammatory cytokines, didn’t you?

Mark Charbonneau, PhD: We did, yeah. We looked at all of the above. We looked at variety of inflammatory cytokines in the clinical study. As Alicia mentioned, what we’ve shown in many of our in vitro models, and even in our preclinical models, is that Bōndia can reduce those inflammatory signals, particularly in the context of inflammatory challenge. In the clinical study, we measured that in the blood and we did not see significant differences in CRP and some of these other metrics like IL-6 in the blood, but we did see the CTX difference and the bone loss difference, right? So presumably the anti-inflammatory connection is there.

Mark Charbonneau, PhD: What we think is that it may be a distinction between what’s measurable systemically and at distal body sites versus what’s happening locally in the tissue and that if you were to look locally in the tissue– For example, in our mouse study, we were able to do gene expression profiling in the spine and that’s where we saw really strong differences in things like tumor necrosis factor alpha–

Alicia Ballok, PhD: And IL-6.

Mark Charbonneau, PhD: And IL-6, yeah. So we think it’s a tissue level difference where that’s happening.

Dr. Kara Fitzgerald: That’s fascinating. Well, Alicia and Mark, thank you so much for joining me today on New Frontiers. I look forward to continuing the conversation with you.

Mark Charbonneau, PhD: Thank you so much for having us.

Alicia Ballok, PhD: Thank you so much.

Dr. Kara Fitzgerald: I hope you enjoyed my conversation today with Dr. Alicia Ballack and Dr. Mark Charbonneau. Is it interesting or what? The world of the internal microbiome in edible plants. How extraordinary is that? We’ve already started using Bōndia in clinical practice and just understanding what they’re up to over at Solaria, I’m excited to see the future products coming forward. Potently anti-inflammatory, really important players in our functional/systems medicine toolkit.

Alicia Eve Ballok, PhD is Director of Discovery at Sōlaria biō, where she leads efforts to develop plant-derived synbiotics for inflammatory and immune-mediated diseases. Her work focuses on uncovering the mechanistic underpinnings of host–microbe interactions, translating complex microbial biology into rationally designed therapeutic strategies. She earned her Ph.D. in Microbiology and Immunology from Dartmouth College and completed postdoctoral training at Harvard Medical School and Massachusetts General Hospital. Alicia has authored numerous peer-reviewed publications and is an inventor on multiple patents spanning microbial innovation and therapeutic application.

Mark Charbonneau obtained his PhD in Computational and Systems Biology in the laboratory of Jeffrey I. Gordon at Washington University in St Louis, studying the interactions between infant gut microbial communities and growth in animal models of undernutrition. Mark has over a decade of experience in microbiome research, bioinformatics and live biotherapeutic development and a passion for advancing biotechnology solutions that leverage the microbiome to improve human health and nutrition. This work led him to join Sōlaria biō, a consumer health brand focused on scientific innovation that benefits patient health.

Clinical Trial Highlights

Marcus Institute for Aging

Join the Research Study – Synbiotic to Attenuate Resorption of the Skeleton (STARS)

Research Articles

A randomized, double-blind, placebo-controlled clinical study to evaluate the efficacy of the synbiotic medical food, SBD111, for the clinical dietary management of bone loss in menopausal women

A synbiotic medical food improves gut barrier function, reduces immune responses, and inhibits osteoclast activity in models of postmenopausal bone loss aligned with clinical outcomes

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Podcast: Resolving Osteoporosis and Optimizing Bone Health – A Tour de Force Update

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Podcast: The Oral Microbiome: The Hidden Biomarker Driving Aging, Fertility & Systemic Inflammation

Bio Age Self Assessment Quiz

Younger You book

Better Broths and Healing Tonics book