Live biotherapeutic products are rapidly changing the landscape of infection prevention, particularly in immunocompromised patients. Among these, SER-155, a multi-strain oral therapy, has demonstrated compelling clinical results. In a recent trial, the incidence of bloodstream infections (BSIs) dropped sharply in the SER-155 group compared to placebo (10% vs. 42.9%). This finding signals a potential breakthrough in both infection control and microbiome modulation. In this interview, Dr. Doris Ponce discusses the mechanisms behind SER-155, its implications for antimicrobial resistance, and its future applications beyond transplant medicine. Her responses provide an in-depth look at how microbiome science is poised to transform not only prevention but also personalized therapeutic strategies in clinical care.

Q1: This study showed that the incidence of bloodstream infections (BSI) was significantly lower in the SER-155 group compared to the placebo group (10% vs. 42.9%), is this result mainly attributed to the competitive colonization of the strain, intestinal barrier repair, or other mechanisms?

Dr. Doris Ponce: Thank you for the question! So just to explain what the live biotherapeutic products (LBPs) or the bacterial live biotherapeutic is. For this particular product, it’s a multi-strain, which means that we have multiple bacteria and they’re all unique, encapsulated for oral use. So these bacteria have been selected with a purpose, and they have a desired functional property. The functionality of them together is what we believe is responsible for this effect that we observe.

These bacteria—we know that they have different properties, so it’s a combination of them. They can inhibit GI pathogens—for example, Enterococcus or pathogens that are not supposed to be in the gut microbiome causing monodomination. But they can also promote mucosal and epithelial barrier integrity and drive anti-inflammatory immune responses.

So the effect together, with the multi-strain, with the multi-functionality, and on top of that, for those bacteria to engraft and occupy the gut microbiome of the patient, is what we think is the explanation of why we observe less infection—bloodstream infection—in the patients that were treated.

Q2: With over 50% reduction in days of antibacterial use in the SER-155 group (9.2 vs. 21.1 days), is this likely to reduce the risk of antibacterial drug resistance? Are there plans to assess the long-term impact of this drug on the transmission of resistance genes?

Dr. Doris Ponce: So what we know is that in other microbiome studies, the exposure of bacteria to antibiotics facilitates the development of resistant genes to antibiotics. We did a study—aside from this one—in our patient population with graft-versus-host disease affecting the lower GI tract, where these patients had been exposed to antibiotics more frequently. And we observed in their analysis the presence of predictors of antibiotic-resistant genes.

So we know that patients who are exposed to antibiotics are more likely to develop these resistant genes than the ones who did not. This is a potential analysis that will be done in the future. Right now, it was not part of our secondary aim, but this is certainly something that we will be asking ourselves, since we observed that the bloodstream infection incidence was significantly lower.

Q3: In future studies, which directions does the team plan to further explore the potential clinical value of live biotherapeutic products in microbiome manipulation?

Dr. Doris Ponce: So in my opinion, we just started to understand how the microbiome can influence clinical outcomes. And as of right now, we observed that there is a favorable decrease in bloodstream infection. But the benefit of a live biotherapeutic product—or manipulation of the gut microbiome—we’re really just scratching the surface.

We believe there could be benefit in other aspects. For example, the functionality of the microbiome. In other words, the microbes in our gut produce byproducts that are only produced in the microbiome—like secondary, tertiary bile acids, short-chain fatty acids—and also an impact in immune reconstitution.

For the future, those are questions that we would like to explore as well. And then also thinking about if treatment should be customized for each patient. For example, if we are able to have a fast test to assess for microbiome dysbiosis, maybe we will customize treatment for those who have a dysbiotic microbiome. Or if we observe certain complications or certain clinical events, we might manipulate the microbiome of those patients based on data.

So I think the future is becoming more customized to patient disease and event, and it will be maybe not only for prevention, but for other situations, such as for therapeutic—like graft-versus-host disease, refractory graft-versus-host disease—or other settings outside of the realm of transplant. For example, like checkpoint inhibitor colitis, or non-malignant GI conditions.

Doris M. Ponce, MD, MS, is director of the Graft-versus-Host Disease (GVHD) Program and cochair of the Center for Hematologic Malignancies Research Council at Memorial Sloan Kettering Cancer Center (MSK).

Dr Ponce is a hematologist-oncologist with specialized postgraduate training in bone marrow transplantation (BMT) and a master of science in clinical trial design. Her academic career is dedicated to patient-oriented research, with a focus on GVHD, which is a major complication of BMT. At MSK, she leads the entire GVHD research portfolio and oversees a multidisciplinary GVHD clinic. She is an active member of the MSK Medicine Steering Committee and served as a member of the Institutional Review Board for 8 years.

Nationally, Dr Ponce contributes to the Blood & Marrow Transplant Clinical Trials Network (BMT CTN) as a protocol team member for the 2303 study and has served on the BMT CTN Toxicity and Supportive Care Committee since January 2024. She is also committed to international education and outreach, regularly participating in lectures and educational initiatives across Latin America.

Dr Ponce recently chaired the first Latin American GVHD Symposium at MSK. Additionally, she is a standing reviewer for the Transplantation, Tolerance, and Tumor Immunology Study Section at the National Institutes of Health, and she reviews for other foundations and institutional research programs.