AMR and the Microbiome Day 1 Part 1

Good morning and thank you to everyone joining us for this public meeting of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria, or the PACCARB. My name is Sarah McClellan and I am the Designated Federal Officer for this Advisory Council. I would like to thank all of our attendees and stakeholders for joining us today, including those who will provide public comment. The goal of this Advisory Council is to give the Secretary of Health and Human Services advice and recommendations to improve the programs and policies related to antibiotic resistance that contribute to the overall health of our country. To accomplish that mission, the Advisory Council strives to address the issues related to antibiotic resistance through a One Health approach, which recognizes the deep interconnection between people, animals, plants, and their shared environment, and is evident in all of our proceedings and products. Before we start, there are a few things you should know. This meeting is being live-streamed and recorded, which will be available on our website at hhs.gov slash PACCARB. Regarding the conflict of interest rules, all 13 voting members of the Council are considered special government employees, or SGEs, and are subject to conflict of interest laws and regulations. The 12 regular government employees, or RGEs, representing different agencies and departments on the Council have also been vetted for any conflicts of interest. Lastly, I would like to thank our Deloitte colleagues, Dr. Cory Meyer, Ms. Lauren Plain, Ms. Jen Roberts, and Mr. Joe Bono, for their efforts to support the Council in the planning and execution of this meeting. I will now go through roll call for all Council members. Please let us know if you are present by stating here. For alternate RGEs, please identify yourself and provide the name of principal you are representing today. Beginning with our voting members, our Chair, Dr. Paul Plummer. Our Vice Chair, Dr. Jason Newland. Dr. Stephanie Black. Dr. Claire Burbick, joining us online. Dr. Virginia Fate, also joining us online. Dr. Susan Wong. Dr. Jenny Kwan. Dr. Lynn Mark. Here. Dr. Payal Patel. Here. Dr. Robin Patel. Here. Dr. Julia Simzak. Here. Dr. Thomas Whittem. Here. Moving to our liaison members. Dr. Jacinda Abdul-Mutakabir, for the American Society of Microbiology. Here. Dr. Mark Papage, for the American Veterinary Medical Association. Here. Dr. Henry Skinner, for the AMR Action Fund. Here. Dr. Padmini Srikanthaya, for the Bill and Melinda Gates Foundation. Here. Dr. Francisco Zagmit, for Epi-X Analytics. Here. Dr. David Jenkins, for the International Society of Antimicrobial Chemotherapy, who is joining us online. Here. Dr. Lucas Pantaleon, for the National Institute of Animal Agriculture. Here. Now for our regular government employees. Please be sure to indicate if you are covering for the principal RGE. For the U.S. Department of Agriculture, Dr. Roxanne Metroni. Here. Dr. Chelsea Shively. Here. Dr. Andrea Koch. Here. For the U.S. Department of War, Dr. Paige Waterman. For the Department of Health and Human Services Administration for Strategic Preparedness and Response, Dr. Mark Albrecht. The Agency for Research Healthcare and Quality, Dr. Melissa Miller. Here. For the Centers for Disease Control and Prevention, Mr. Michael Craig. Here. For the Centers for Medicaid and Medicaid Services, Dr. Sherry Ling. I'm Shelly Coyle, in representation of Dr. Ling. Welcome. For the National Institutes of Health, Dr. Sam Perdue. Here. For the Office of Global Affairs, Ms. Angela Monaghan. Here. And for the U.S. Food and Drug Administration, Dr. Bill Flynn. And finally for the... Welcome. For the Environmental Protection Agency, Dr. Jay Garland. Here. Thank you all. I'll now pass it over to our co-chairs, Dr. Paul Plummer and Jason Newland, for a few opening remarks. Good morning and welcome to the 28th meeting of the Presidential Advisory Council on Combating Antibiotic Resistant Bacteria on Harnessing the Microbiome for Combatting H1N1. I'm honored to open the meeting today and make space for such an important discussion that gives us an opportunity to step back and explore broader questions about the intersection of the microbiome and its impact. How do microbiomes influence AMR? How can the field expand PACCARB's thinking about AMR prevention, treatment, implementation of interventions, and the future strategies? The microbiome is increasingly recognized as an important influence on health and well-being of people, animals, and the environment, including related to infectious diseases and AMR. Traditionally, AMR discussions often focus on specific pathogens, resistance mechanisms, and drugs across the surveillance and stewardship domain. While those focus areas remain essential, the microbiome has an important dimension because it helps determine how microbial communities within and between hosts and across sectors can influence resistance, treatment, and prevention of infection. As we begin, I want to encourage our speakers to help all of us understand not only what the microbiome shows, but why it matters for AMR. This meeting is an opportunity to connect microbiome science to the larger AMR landscape in a way that supports shared understanding of future action. We also must keep the practical end point in mind. The scientific advancements you'll hear about today are promising, and all of our stakeholders, policy decision makers, clinicians, veterinarians, public health practitioners, and patients will want to know how these insights can move from research to practical interventions that provide measurable improvements in care and outcomes. With that said, we have a full agenda, and we will get the most value from today if we stay focused on surfacing clear, actionable insights that can inform future recommendations. With that, I'm pleased to turn it over to our vice chair, Dr. Jason Newland, for his opening remarks. Thank you, Dr. Plummer. I want to echo that welcome and underscore the importance of the discussion ahead. I am just actually extremely excited to see this room so filled and all the people online. We're going to have an awesome day today and tomorrow. We have a great opportunity before us to consider the microbiome not as a separate issue from antimicrobial resistance, but as an important part of how we understand the conditions that shape resistance, success of treatment, and resilience to future infection. As we look at AMR through this lens, it is, of course, critical to ask how we want, as emerged, but it's also important to understand why it might emerge and how the conditions will are available to do that and where the microbiome plays in. The microbiome also gives us a way to examine those conditions across people, all people, including children. Remember, I am a pediatrician. As well as how it intersects with animals and environment, and that's what's been a, I would say, the success of this council is that One Health Program, that notion that me as a pediatrician went and saw Dr. Widom at the vet school at Ohio State. That is what has led us some of the great work that we have done and will do. This meeting is then one of the first steps in exploring this connection between AMR and the microbiome, as well as considering where microbiome science can strengthen future strategies to address this problem of AMR. Okay, so with that in mind, I really look forward to hearing from all of our speakers who have come from afar, who are online, about this state of the microbiome science and what is still needed. I'm also looking forward to all the brilliant people sitting in this room for all their great comments that we're going to hear from the PACCARB and how we, as PACCARB, can elevate the most actionable opportunity for the future. So with that, I will turn it over to our esteemed leader, Claire McCullough. All right, thank you both so much. I have a few quick housekeeping reminders. Council members, if you wish to ask a question or have a comment during Q&A, please simply turn your name tent vertical. For our online council members, please simply raise your virtual hand and the moderator for each Q&A session will call on you to speak. Once called on, please unmute your microphone before speaking and mute it again after your comment or question. Please speak directly into the adjustable microphone to ensure that everyone in the room and our colleagues online and those watching the live stream are able to hear you. All right. With that, it is now my privilege to introduce Mr. Connor Semelsberger, Chief of Staff to Admiral Brian Christine, the 18th Assistant Secretary for Health at the U.S. Department of Health and Human Services. In his role, Mr. Semelsberger supports the Assistant Secretary for Health's efforts to restore trust in public health, promote transparency, and strengthen the health of the nation. We are grateful to have him with us today, particularly as this council discusses antimicrobial resistance and the importance of keeping our national response current, science-based, and action-oriented. Mr. Semelsberger, thank you for joining us. The floor is yours. Good morning, everybody. Can you guys hear me okay? Awesome. Yeah, as Ms. McClellan said, my name is Connor Semelsberger and I'm here on behalf of our Admiral Brian Christine, the Assistant Secretary for Health in the office for the Assistant Secretary for Health. He regrets that he couldn't be here today, so unfortunately, you guys are stuck with me this morning. I was just floored as I came in today. So much enthusiastic discussions already prior to the meeting even starting, so it's great to know there's so much enthusiasm for the microbiome, so thank you for hosting me this morning to kick everything off today. It's a pleasure to be with you, and I want to thank the members of PACCARB for your continued leadership and commitment to addressing one of the most pressing public health challenges of our time, antimicrobial resistance, or AMR. As we advance the administration's vision to make America healthy again, combating AMR remains a critical priority. Today's focus on harnessing the microbiome as a method to combat the AMR crisis highlights a promising and increasingly important part of the effort with the potential to strengthen the health of the American people. Antibiotics have transformed modern medicine and continue to save countless lives, yet antimicrobial resistance is a growing threat, contributing to an estimated 1.27 million deaths worldwide each year. In the United States alone, more than 2.8 million antimicrobial resistance infections occur annually, resulting in over 35,000 deaths, way too many. That reality reminds us that preserving the effectiveness of antibiotics will require continued stewardship, ongoing innovation, and a commitment to exploring new approaches that can help prevent infections and reduce the need for these treatments wherever possible. That is where the microbiome, the focus of this public meeting, offers real promise as an emerging area of opportunity to combat AMR. As we learn more about the microbial communities that support human, animal, and environmental health, we gain new insights into preventing disease, strengthening the resilience, and creating the conditions that allow healthy microbial communities to thrive across people, animals, and the environment. Protecting these interconnected systems through a One Health lens can help reduce the spread of disease, advancing our Make America Healthy Again goals, and protecting America's health. It's so great to see representatives from so many areas of medicine, but even across our own government to be here, from USDA, DOW, to, you know, our in-house offices here within HHS. And this challenge is complex, but the breadth of expertise gathered here gives us reason for optimism. By bringing together these perspectives from across sectors and disciplines, we can turn scientific insight into practical solutions and chart a stronger path forward. Thank you for your dedication to this important work. I look forward to today's discussion and to the valuable recommendations that will help advance the responsible, evidence-based use of microbiome science in our nation's response to antimicrobial resistance. Thank you, and enjoy the rest of the next few days. Thank you, Mr. Simmelsberger, for joining us and for lending your perspective to today's discussion. It's now my pleasure to introduce Ms. Alice Hernandez and Dr. Betty Chow, who can join us at the table down here at the end, who will be sharing Rosie's story. Rosie is an energetic pit bull mix whose long journey with chronic gastrointestinal disease ultimately led to the use of a fecal microbiota transplantation. Please join me in welcoming Ms. Hernandez and Dr. Chow as they now share their experiences caring for Rosie. Hi, can you hear me? Okay, great. My name is Alice Hernandez, and I'm Rosie's pet parent. Thank you to PACCARD for inviting me to speak today. It's been a really long journey, and I'm grateful something good is going to come out of it. We adopted our little wild child in November 2018. Next slide, yeah, okay. If you can't tell, she's our little wild child. My two-mile-a-day hikes were nothing to put a dent in her energy, so we decided to hire a dog who would take her on very long hikes in order to get her a little tired. We live happily like this for the next few years, where she was healthy and in perfect shape. Next slide. It wasn't until 2022 when things got a little interesting. Someone fed her grapes, not us, and she was bitten by a rattlesnake while protecting our family in our backyard. It wasn't until August of 2022 when the dog walker brought her home after a long hike and told us that she couldn't keep up, again, very much not like our wild child. We rushed her to the hospital, and after several days and several tests, she was diagnosed with Kidney Disease. As you can tell, I do not have a science background, and I did not know what that meant. We took her to all our appointments and gave her all our meds, and she still wasn't improving. By some chance, we decided to move her to a different hospital, and that is when Rosie met Dr. Chow. I wanted to publicly thank Dr. Chow for her relentless pursuit of ulterior treatment and the grace that she showed us during this difficult time. So, thank you, and spoiler alert, she's our little wild child again. Thank you. Next slide. So, I met Rosie around December 2022. At the time, I was treating their other dog also for chronic enteropathies with GI disease, and so when I met Rosie, she had soft stools at the time, kind of bearing to diarrhea with mucus. She was a napkin. She had signs of nausea, and she also had all the classic signs of basically losing protein, losing albumin, edema peripherally. She had a slight use of fluid in the belly. She was underweight. She had poor muscle condition score, and from her previous internist that diagnosed her with protein-losing nephropathy, which is where you lose protein through the kidneys, she was on a drug called Telmisartan to kind of control that. She was on a blood thinner, blood pedigree. She was on a renal diet, which I'll get onto in a second. All appropriate treatment for that disease, and she had adjusted the dose about a month before I saw this dog because the urine protein cranium ratio way to analyze and evaluate the urine protein loss was appropriate, which seemed fair. Unfortunately, her protein dropped again, and just based on her history and clinical signs, something didn't add up, and I suspected she also had protein-losing enteropathy, which is where you also lose protein through the gut, and so what I initially did with that dog is that we changed her renal diet, which is a high-fat diet. While appropriate for her nephropathy, it was inappropriate for what I suspected was a protein-losing enteropathy at the same time, and so we kept her with a novel protein diet that was moderately protein-restricted for the kidneys but dropped the fat, and I also increased the fiber content on her diet because a lot of these kidney diets are also very low in fiber. I did also put her on omega-3, which is appropriate for the kidneys, although in hindsight, I probably should have maybe waited a couple weeks, two months before I added that in just in case she's fat and tolerant, and I increased back the time of starting dose just in case the kidneys was also a part of not what being controlled just so I can deal with one thing at a time. Next slide, please. And so she did improve. Her soft stools were more soft and less diarrhea, although that progress stagnated. Her albumin did increase from 1.2, which is pretty low, down to up to about 2.1, and then low normal at 2.6, but it just kind of hung there, and for a lot of these dogs, we really are aiming for at least three or above if we could get the albumin off. She had more pronounced weight loss, and part of it is probably because her fluid accumulation kind of died down a little bit, so she was less puffy in general. It kind of revealed her true lean muscle mass loss. We increased the time of starting again because her urine protein content ratio was still a little high. I didn't like that, and I also adjusted fibers, so we're kind of managing kidney and GI at the same time. Next slide. And so she continued to have loose stools. Three months later, she continued to now lose even more weight. She now also developed neoregurgitation, and she had worse appetite, and at this point of PLN, her nephropathy was actually very well controlled, and her albumin unfortunately actually got worse, which kind of proves the point that I do think she was losing protein from her gut. She also had gastric ileus, so her gut wasn't moving very well, and on ultrasound, she had gastric wall thickening, pretty consistent with gastritis, and so we hospitalized her at that time because she wasn't feeding at all on prokinetics and just supportive care to just get her through the hump. Next slide. And we checked about a week later. She did have continued ileus. Her diarrhea was worse. Basically, her GI was just going nowhere, and at that point, we decided to try low-dose immunomodulatory therapy, which is kind of—it depends on the dog whether or not they respond to immunomodulation, so in dogs, it's a little different from humans where a lot more of them are diet responsive and less so immunomodulatory responsive, but we decided to just try, and because of her nephropathy, we didn't want to use steroids to make it worse. I was avoiding cyclosporine just because there were some human reports potentially worsening that, and we kind of just didn't want to take the risk, so we did microphenolate, which is the drug we do use for protein-leasing nephropathy, but we kept those low in case of GI side effects. Her ileus did improve a little, and her clinical signs kind of improved a little bit, but her albumin was still pretty terrible at 1.8, and so that's when we discussed the use of sleep and microbiome transplantation. Next slide. And so we have a validated index, which unfortunately, it seems like—oh, yeah, if you could stop clicking—oh, yeah, great. So we have a validated index that we—it's basically using quantitative PCR to assess seven key bacteria in dogs and also in cats to evaluate dysbiosis in our patients, and we validated different bacteria species for dogs and cats and for sofa dogs. These are what's listed on the screen. I'm not going to go into detail about that. However, essentially what you can see on that graph is anything below zero is normal. Zero to two is equivocal on dysbiosis, and above two is definitely abnormal microbiome, and Rosie definitely had over to whale. And so we knew she was dysbiotic, and there has been a retrospective study kind of looking at some of these dogs that the more dysbiotic they are, the more likely they may respond to FMT, and so we decided to go for FMT, and this is actually Blue, the donor for a lot of Rosie's fecal transplant. She's a dog in Texas. Unfortunately, she had to be retired recently because her housemate unfortunately got giardia. A bit unfortunate, but there has been a clinical guidelines published for FMT in companion animals, which I won't go into, but I've inserted a QR code in case you wanted to read that paper. Next slide, please. And so by April, we started FMT on Rosie. We did two FMTs at two-week interval to kind of load her by a rectal enema, and then we actually continued monthly, and part of that decision was because every five weeks or so, she would clinically relapse in clinical trials, and so we decided to do every four weeks or so, and that seemed to do her in a good shape. She had pretty minimal to no post-FMT side effects. At first, she had mild transient anaphytens, and she may have vomited once, but otherwise, she tolerated it pretty well. Next slide, please. And so after about two or three FMTs, she actually did start to gain weight for the first time in many months. She had improved energy, and her stools were actually relatively normal, and her albumin did also, over a couple of months later, normalize to about 2.8. I still don't like that, but that's significantly better than much before that. Her dysbiosis index also eventually improved, and this is her graph kind of showing her dysbiosis for about two years or so. What's interesting with her, and we can't quite explain why, is why she does this kind of a little dance. She kind of goes up and down, and up and down, and up and down, but eventually does kind of down, and we did also discontinue mycophenolate after three months, because we didn't think it was doing that much, and she's not clinically relapsed, and so you can see on that graph before, there was that red bar where the DI kind of went up significantly, and that's what happened in April 2024, when she got pretty sick. So up until that point, she was doing really well, and then she developed acute vomiting and hemorrhagic diarrhea. She was also in use for PNAG, so I suspect that she was septic, which kind of forced my hand to use antimicrobials, because she was clinically pretty in that shape. She was hospitalized for six days, and I ruled out infectious causes, then we diagnosed her with something what we call acute hemorrhagic diarrhea syndrome in dogs, and then that's based on a particular testing that I won't go into, but essentially it is a non-infectious cause of acute hemorrhagic diarrhea in dogs that we recognize that they generally won't kind of get through, but some dogs can, unfortunately, and and so you can see in that red bar, that's where the DI kind of shot back up, and we do recognize that in dogs with AHDS, they do have transiently worsened kind of dysbiosis, but what we suspect had happened was she's already a dog with a compromised microbiome, and the AHDS kind of just hit her pretty hard, and we also unfortunately had to use antimicrobials, which probably makes things worse. We then resumed her monthly schedule of FMT, and she actually continued to recover and do well, and she actually by the end of 2024, kind of mid-2025, she actually started gaining way too much weight, and she was a little overweight. We had a conversation about this. Her albumin also normalized to over three, and her DI did, as you can see, eventually normalize again. Obviously that graph only goes to end of 2024, but that's kind of where she stayed for another year or so. And so we, during all of that time, we weren't just relying on FMT. We were using that clinical response to give us time to fiddle with diet, fiddle with fiber, and then mid-2025, we decided why don't we try another immunomodulation drug, just to see can she eventually get off the reliance of FMT. And so we did do a low-dose glutamide, and by the end of 2025 or so, we actually started spacing the FMTs out from four weeks to six weeks, down to eventually every 10 weeks or so, and her DI did gradually increase, which is to be expected, because the FMT was kind of kind of suppressing it down and making it more normal, but she clinically did continue to do well. And that was until, being an overachiever, she decided to blow through this. So she was a purely a therapeutic. Her back legs weren't moving. I got panic texts from Alice and also my ER staff at my hospital that they had to refer her to a neurologist. On MRI, she blew T11 to L1. She had to get hemi-laminacnea on three of the spaces. The neurologist, fortunately, was aware of the fact that, of her medical history, and avoided antimicrobials at all costs, which I was very thankful for. And during that time, she did have a delay of FMT treatment, but she had no GI relapse, which was really possible for her, and she eventually recovered from her neurological disaster. And so the last time I saw Rosie was actually April 2026, because that was around the time when I left Los Angeles for private practice. And that was, she was already on every 10 weeks of FMT, and she continued to clinically do well. She was still overweight, and as of our conversation yesterday, she is still overweight. And so we have been intermittently checking her GI. So I think we checked it around June time, and it was actually pretty stable, and she clinically is doing very well. And so this is the retrospective series from Sweden that I mentioned, it's the biggest case series that we evaluated 41 dogs with FMT for adjunct treatment for chronic enteropathy in dogs. And it shows that it is efficacious in adjunct therapy in canine chronic enteropathy. Although we do see that some dogs require not just one or two, and some dogs even three treatments before you see a response, and that's why we decided to load her at first. What was helpful with the use of FMT is that this allowed us to avoid antimicrobial use for chronic enteropathy, which unfortunately is still very much a trend in veterinary medicine. It is an easy way out. Things like metronidazole, tylosine does suppress clinical signs, but it worsens the microbiome, and it's not sustainable. Clinical signs often may relapse, it doesn't treat the underlying problem. And so we are trying to push towards moving away from that culture. But what this did allow me to do is kind of buy me more time to experiment with other therapies because the dog was clinically doing well on FMT. And it allowed me to kind of fiddle with things nutritionally and with drug management without clinical relapse. Next slide, please. And so we did actually publish this case, that is the case report late last year. And this is, and the photo is actually one of my former medicine interns who's now a medicine resident at Colorado State, Dr. Schreiber. So he helped us write up this report, which kind of detailed a lot more about the case. Next slide, please. And so I'd like to thank the Texas A&M GI Lab and Dr. Young at the GI Lab who have kind of provided me with the lyophilized stools that we were able to use for Rosie's FMT, because at that time in private practice, I did not have the resource to manage my own bank. And Dr. Schreiber, who I mentioned, who wrote up the case, and I'd like to also thank the organizers for inviting us to speak. I know there's no Q&A, but I put my email there and you're welcome to reach out if you have any questions about that. Ms. Hernandez and Dr. Chow, we certainly appreciate you sharing that story with us. It's been a longstanding tradition at PACCARB meetings to start the meeting with a patient story. And occasionally we like to mix it up and have a One Health one. So really appreciate you sharing that. It grounds us in thinking about why we're here and what we're going to visit about for the next few days. So with that, I'm going to turn it back over to Sarah. Thank you, Paul. Earlier this summer, PACCARB established a microbiome subcommittee to help inform the council's ongoing exploration of microbiome-related topics. I would like to welcome Dr. Horrigan to give a presentation. Dr. Horrigan is a Lassiter Clinical Research Scholar and Chief of the Clinical Microbiome Unit at NIAID NIH, where she leads microbiome interventional trials in early life focused on reducing the risk of chronic inflammatory diseases. She serves as Chair of the Microbiome Subcommittee and will present findings from the meeting, the inaugural meeting of the subcommittee that was held on September 2nd last week. I'm pleased to welcome Dr. Horrigan and have her share the update. The floor is yours. Thank you so much for the kind introduction. And thank you to the PACCARB Council for this opportunity to share a brief summary of the inaugural HHS Microbiome Subcommittee Roundtable, which took place here in this room last week. Next slide. I want to say how much I appreciate being part of this broader PACCARB ecosystem. The work this council has done over the many years has been extraordinary, and it was wonderful to see today's agenda. I look forward to learning a lot from the panelists. Let me start with our charge. HHS convened a group of leading microbiome experts with a focused mandate to examine the current state of the field and discuss a strategic vision for future research priorities with the goal of generating insights that are meaningful and actionable for the public and healthcare professionals. I want to acknowledge up front that we did not address, oh, back one slide, please. I'll say next slide. I want to acknowledge up front that we did not address two critically important barriers. Firstly, antimicrobial resistance, and secondly, agricultural and veterinary microbiome science. Those fields have deep expertise here, and we would not presume to speak to them. Our focus was deliberately on human health dimension of microbiome science, and I believe what I share today will be complementary to the broader work of PACCARB. Next slide. It was my honor to chair this international panel of microbiome experts with Dr. Kwon joining us as the PACCARB FTE. I suspect many of you will recognize or have collaborated with a number of the scientists in our group, including Marty Blazer, the founding chair of this very council. Rather than introduce everyone individually, I will simply say that the breadth of expertise assembled was remarkable, spanning the full spectrum of human microbiome science. Computational metagenomics and methodology, functional microbiome and the virome, immunology, nutrition, and metabolism, the gut-brain axis, early life and infant microbiome, cancer research, clinical translation, regulatory science, with FDA representation at the table, and precision medicine. Next slide. The opening discussion established a shared foundation. The field has transformed. We have moved from descriptive cataloging, simply asking who is there, to increasingly mechanistic and translational science that can demonstrate causality and point towards clinical intervention. High-throughput sequencing and multi-omic have established strong associations between the microbiome and a wide range of diseases. Metabolic, neurological, immune-mediated, cancer are just a few. And crucially, the microbiome is now understood as a connected organ system, deeply interwoven with immunity, the nervous system, and our responses to drugs and therapy. But the group was clear-eyed about what remains to be done, establishing causality in humans, moving beyond DNA sequencing to true functional understanding, improving reproducibility, and ensuring our findings reflect diverse global populations. These are foundational challenges the field must address. Next slide, please. On the basis of current evidence, the group identified a number of recommendations for supporting a healthy gut microbiome, things we can say today with confidence on a mostly common-sense general advice. Dietary diversity, fiber, fermented food, antibiotic stewardship, supporting vaginal birth and breastfeeding where possible, and lifestyle factors such as sleep and physical activity. I also want to flag two areas of caution the group felt strongly about. Direct-to-consumer microbiome testing, where the evidence that results lead to meaningful, actionable outcomes is currently weak, and commercial probiotics, where marketing frequently outpaces the science. We felt these were important public health messages. Next slide, please. The heart of our discussion was identifying 10 strategic research priorities. I will walk through these briefly. Next slide. The first two priorities are foundational. We need to move beyond observational data to controlled interventional studies, and we need better integration of animal model and human data to reduce translation failure. Strain and function level resolution through long-read sequencing and culturomics are essential. The second priority, scaling and infrastructure, is one we feel particularly strong about. Large-scale U.S. microbiome studies are critically underfunded, with major efforts currently being led by other centers. We need federated computational infrastructure, AI and machine learning to integrate complex multi-omic data, and coordinated policy to resolve the international data transfer barriers that prevent us from building the truly global data set that we need. Next slide. Priority three addresses a fundamental limitation. DNA sequencing tells us who is present but not what the microbes are doing. We need multi-omic approaches with metatranscriptomics, metaproteomics, and metabolomics to capture actual function. One insight I felt particularly exciting from our discussion was that of microbially-derived metabolites as a therapeutic avenue that may be more tractable than live bacterial consortia, and potentially easier to navigate through the existing regulation framework. Priority four addresses the virome and other underrepresented components of the microbiome, bacteriophages, melanoviruses, fungi, archaea. This connects directly to the phage therapy work you'll hear about later today, and underscores the importance of expanding beyond bacteria in how we think of the microbiome. Next slide. Priority five is regulatory science and translation. FDA-approved FMT-based products are a real milestone, but frameworks for live biotherapeutics, microbiome diagnostics, and physician nutrition lag significantly behind the science. We need rapid approval pathways for safe intervention, such as dietary and phage phage, that currently fall between existing frameworks. And microbiome endpoints, where scientifically justified and validated, must be integrated into standard topological safety assessments. Priority six reflects the inherently individual nature of the microbiome and the opportunity it presents for AI-driven nutrition and microbiome-informed therapeutic strategy. One size will never fit all in this field. Priority seven, and this is my own interest, so I have a little bias here, but the first thousand days of life represent perhaps the highest return window for microbiome informed prevention. The microbiome develops during this period with lifelong consequences for immune, metabolic, and neurodevelopmental health. Antibiotic exposure before the age of two and cesarean delivery, both of which alter the developing microbiome, are associated with an increased risk of metabolic and atopic. The evidence we most urgently need is from large scale prospective longitudinal studies beginning in pregnancy and following children beyond adolescence. This is where prevention-focused investment offers the greatest long-term public health results. Priority eight, the gut-brain axis is one of the most compelling and urgent frontiers in our discussion. The microbiome is implicated as a contributing factor in Parkinson's disease, Alzheimer's disease, and autism spectrum disorder. Parkinson's is the world's fastest growing neurological disorder. Alzheimer's is projected to affect nearly 14 million Americans by 2040, and yet less than 15 percent of neurodegenerative disease research currently targets prevention. Microbiome informed prevention in this area is high return and critically underfunded. Priority nine, the cancer microbiome field was highlighted as a proof of concept of what microbiome science can achieve. The gut microbiome is now an established determinant of cancer immunotherapy response, and rapid advances at the gut-tumor interface, including causal mechanisms, biomarkers, and interventions, show us what is possible when the scientific and translational conditions arise. The group felt strongly that the lessons learned from cancer microbiome research and the pace of the progress achieved should be applied to other chronic conditions. Our final priority, and perhaps the most important, was public and professional education. Microbiome science must enter medical school curricula and healthcare professional training. Clear evidence-based public communication is needed to distinguish validated interventions from unsupported commercial claims. And school-based nutrition education, along with removing harmful ultra-processed food from federally funded school meals, represents a practical, near-term action. On closing, what struck me most about our inaugural roundtable was the alignment in the room. Alignment across disciplines, countries, and crucially, alignment between what science is telling us and what federal health priorities are calling for. With sustained commitment and strategic investment, we believe that the strategic priorities described have the potential to meaningfully reduce the burden of chronic disease across the lifespan and to position the United States as the global leader in microbiome science and its translation into human health. However, this will require the kind of federal investment and coordination that bodies like this council are uniquely placed for. Thank you. I look forward to your questions. Thank you, Dr. Horrigan, for sharing the output of the recent subcommittee meeting. We will now transition to a short Q&A. As a reminder, council members who wish to ask a question or make a comment should turn their name cards upright or raise their virtual hand. Dr. Horrigan, thank you for the wonderful presentation and the summary. I also love the first 1,000 days of life, so I'm with you on that. When I think a lot of us think of microbiome, we think of the gut. So there's microbiomes in your mouth, there's microbiomes on your skin. What was the conversation beyond just, I think, the assumed gut microbiome? Were there other discussions with this? No, absolutely. So the vast majority focused on the gut microbiome because that's where we know the most. But we know the skin microbiome is associated with the development of atopic dermatitis. We know oral diseases, like periodontitis, are associated with changes in the oral microbiome. So I think these are also very underexplored areas that deserve more attention and more funding. Wonderful work. Great work there. I did have a question concerning or just thinking about the intersection between chronic diseases and the microbiome and the variants there and how we would consider those folks that are more likely to have a chronic disease to likely have an altered microbiome that would then increase their chances of resistance. So as you all are doing this research, is there consideration about maybe those geographical areas? I saw the representation of the countries, but even considering highly vulnerable areas of the United States where there may be priority and investigation or even, like, as you're considering the data that you receive, really accounting for those areas where we do see, like, increasing chronic illnesses. I'm thinking about, like, the southern part of the United States and so on and just the difference in the microbiome. That's a great question. There is a lot of variation between chronic disease and geographical areas. You know, one of the priorities that was identified is actually looking at the microbiome changes that occur before those chronic diseases actually show themselves because that's your biggest chance for intervention. If the you can change somebody's microbiome, but it's very hard to change the inflammatory pathways that have already been set in place from early microbiome development. But I think both approaches need to be taken. Any other questions or comments? Anyone online? Appreciate the presentation. I'm curious, what are the plans for the workgroup moving forward? This is a substantial amount of, I think, great information that was shared and I think a great distillation here. Are there plans for the workgroup to do anything else? Absolutely. We plan to meet at least annually, but a great breadth of information was covered this time, but really to go much deeper into a few of those priority topics. We'll certainly publish our viewpoints as well as a group, but we do want to have sustained regular meetings and we'd appreciate hearing how we can best help you as well. Dr. Marks? Thank you. Yeah, very interesting. I was just wondering if you could share your thoughts on the funding situation. Do you feel optimistic about that? Do you think there's a lack of awareness? Do you think there's a mountain of issues? So that's a little bit of a difficult question. As we all know, there are funding challenges right now, but from my understanding, HHS is very committed to microbiome science and improving human health, so I'm very hopeful that this space could receive more funding. Any other questions? We have time for a few more. Ah, Dr. Jenkins online, please. Thank you very much, Sammy. Microbiome research is really fascinating and this was a wonderful summary of a current position. I didn't see anything about education of healthcare professionals about microbiomes and clearly the things we do in healthcare can potentially impact on microbiome. Is that something that should be included in this work? So yes, I briefly mentioned it on the slide ten, but we went very quickly. So that was definitely a major priority of educating all healthcare professionals. Certainly when Dr. Bhattacharya was speaking last week, he said he didn't know anything about the microbiome until really coming into the NIH and medical students I work with now have very little education. I think it's critical to start there. We know there's lots we don't know, but we know enough to start beginning to educate medical professionals. Yeah, yeah, go for it. You can go ahead and then we'll have your next. I thought it was just one. I was like, oh, wait, it was already one. Just one more question in regards to the microbiome and back to something that Dr. Newland brought up about the different microbiome that we have in our body. So going back to the representation of the committee, I did see that there was an absence of specialties that I would think about when considering the microbiome, especially oral. I didn't see dentists and I didn't see pharmacists. And when I think about just drug delivery, pharmacokinetics, pharmacodynamics, and how that can alter the microbiome, is there an opportunity for collaboration with other groups representing these specialties? Or is there an idea to maybe expand to include them in further iterations of them? That's a great idea and thought. So I would say that all of us on the panel do collaborate with people who work with oral and skin microbiome, although our main focus is gut. But we could certainly consider bringing in some of those specialists too. Thanks for a great presentation. You mentioned the microbiome, especially in the first thousand days of life and links to potentially chronic diseases. Did you also talk about the potential, especially in preterm infants or young infants, for microbiome and altering or interventions of microbiome to prevent acute infections as an intervention? And then if you could maybe expand a little bit on the interesting point you brought up about microbiome metabolites as a potential therapeutic. Absolutely. So I think we'll start with prematurity. So we did discuss that there is evidence now that we know that certain components of a pregnant mom's microbiome are associated with certain kinds of premature birth. And that could be an area for intervention. As we've covered so much, we didn't speak specifically about prevention of infections in premature infants. But there is some good work showing that there are changes in the microbiome several days before infants become septic that you could potentially intervene. And the second question was about the metabolites. So we did discuss about how right now a lot of the focus is on identifying bacterial consortium that we can use as interventions. And there are many different trials across many different diseases. Really the only success so far has been in C. diff infections. But there are things coming down the line. It's very difficult to get these approved. And it takes a long time and even longer for children. As you can see, as we always lag behind in pediatric therapy. Metabolites without the bacteria potentially represent a safer or more acceptable intervention. And I'd love to hear what our FDA colleagues think about that. But there was discussion, could a single metabolite or a group of metabolites without the bacteria that they are normally with have those same effects? But people are doing those trials now, at least in animal models. Dr. Wong? A terrific presentation and really an exciting time to have this subcommittee. I just wanted to second the two comments previously, that I think it would be incredibly valuable to have a slide focused on the next focus for skin and for oral. I think as much as the evidence is so striking at the beginning of life, it's also interesting to see that the microbiome changes on the older age too. And we all age. So I think those things would be important to add in. That's a great point. And we covered a little bit about the aging microbiome under the neurological diseases, but there's so much more than that as well. And I will say we did also touch on women's health and the changes through puberty, pregnancy, and menopause, which are critical. They just did not fall in our top 10 that we had to summarize today. Dr. Zagmet? Thank you very much. Very interesting new priorities. I picked up the first one, of course, about cessation and reproducibility. Of course, we all want that, and we all know the burden of, or I will say, the limitations. But when we talk about the microbiome, especially on the first thousand days, how there are some logistical and also moral problems in performance of randomized controlled trials. I wonder if there is an opportunity to provide guidance on how to perform such studies in this unique kind of setting. That's a great question. And there is plenty of expertise on the panel who work on early life who can speak to that and do controlled interventional trials. And perhaps in our larger publication, I'm going to leave some of that as well. With a group of individual scientists, though, it's very hard to make everybody do the same thing because everybody has their ideas. But we could provide guidelines. Thank you so much for your presentation. I think as we think about antimicrobial resistance, one of the things that struck me in your presentation, which makes sense, is to avoid antibiotics early in life, I think you mentioned. And I think that's in part where what we're working on with resistance intersects with the microbiome. But antibiotics are also lifesaving drugs. And so I think the messaging has to be carefully delivered. We need to use them when they're needed, but not when they're not needed. And can you comment on how you think that could be accomplished or how we could better use antibiotics to not so much impact the microbiome? Great comment. And antibiotics are absolutely needed in certain circumstances, but often they're given when they're not. And an example is in children with otitis media. Most of it's viral and it's going to get better in a couple of days, but there's a lot of parental pressure to have the antibiotic, get the child better quicker if it really does, and get them back to school and work. This is where I think that professional education and public education is really important. And then the provider and family can make their decisions together by having that knowledge. Any other comments? We have time for probably one more. Thank you very much for your comments. And you sort of mentioned the fact that we have a lot of commercial products out there and the commercial products are kind of ahead of the research. You can go to the pharmacy and buy a lot of probiotics and prebiotics. Are you guys planning to have a little bit of research and follow up some of these products or maybe have a little bit more of a suspension approval process for these products without impacting them reaching the consumer? That's a great point. And our conversation around probiotics was a lot of it was there's a loophole. So as long as they're not making a specific claim for a specific disease, they can say inflammatory diseases and metabolic conditions and a whole host and they can make claims but they don't have to go through the same regulatory process. But the advertising and the money put into it to the public, they have really overstepped the science. A lot of the live biotherapeutics coming through, which are for specific diseases, are much more carefully regulated, which is important. I'm not sure does that answer your question? All right. Thank you all very much. And thank you, Dr. Horrigan, again. We are now going to take a quick 10-minute break for our next panel session. All members, please make sure you're back in your seats by 1010 and we'll start promptly back up at 1015. Thank you all. Produced by the U.S. Department of Health and Human Services.