Disclosure: No relevant conflicts of interest to declare.
This session will provide a practical framework for designing microbiome-directed interventional trials in hematologic malignancies. The gut microbiome has emerged as an important determinant of clinical outcomes, with growing evidence linking microbial composition and function to treatment response, survival, immune reconstitution, and toxicity. Although much of this evidence remains observational, advances in high-resolution sequencing, metabolomics, and immune profiling now enable integrated mechanistic studies that can move beyond correlation toward causality. While these mechanistic studies are evolving, their insights are informing therapeutic strategies.
Despite growing interest, few rigorously designed microbiome-directed interventional trials have been conducted in hematologic malignancies and their precursor conditions. This session will equip attendees with a practical framework for designing microbiome-directed clinical trials by highlighting lessons learned from completed and ongoing studies, key considerations for selecting interventions and endpoints, integrating microbiome and immune biomarkers, addressing important confounders, and identifying opportunities to develop novel microbiome therapies.
Dr. Urvi Shah will discuss dietary and prebiotic interventions as broad ecological approaches to microbiome modulation. She will review the rationale and summarize evidence linking diet, the microbiome, and clinical outcomes including NUTRIVENTION trial results. She will highlight key principles and practical challenges in designing rigorous dietary and prebiotic intervention trials.
Dr. Florent Mallard will discuss fecal microbiota transplantation (FMT) as an approach to restore disrupted microbial communities. With a focus on allogeneic hematopoietic cell transplantation (alloHCT), he will review the mechanisms and clinical evidence for FMT in the prevention and treatment of graft-versus-host disease, including the pooled allogeneic fecal microbiota (MaaT013), and discuss its potential to reduce infections. Dr. Doris Ponce will focus on defined live biotherapeutic products as targeted microbial therapeutics. She will review the rationale for using defined bacterial consortia to selectively modulate microbial communities and host–microbe interactions, present clinical data from SER-155 to reduce infections in alloHCT and discuss adaptive trial design implementation in microbiome-directed clinical development.
