Linking the Gut Microbiome to Chemotherapy Toxicity in Pediatric ALL

Dr. Eran Elinav, M.D., Ph.D. – Weizmann Institute of Science, Israel

Childhood acute lymphoblastic leukemia (ALL) is the most common type of cancer in children. While treatments have improved survival rates, many children experience severe adverse effects from chemotherapy, such as life-threatening infections or damage to vital organs. Current methods rely on trial-and-error approaches, while identifying which children are at higher risk for these complications before treatment starts constitutes a significant unmet clinical challenge. In this project, we will harness the gut microbiome, the community of bacteria inhabiting our gut, to predict which children are more likely to experience severe treatment-realted side effects. Together with a leading tertiary cancer center, we will collect host and microbiome data from 250 children newly diagnosed with ALL. Using AI, we will analyze the data to find patterns linked to adverse events and develop personalized AI-based prediction models for leukemia-related adverse effects. Our initial results show that utilization of personalized microbiome data from children prior to the beginning of chemotherapy, and its analysis using AI, enables robust predictability of a variety of chemotherapy-induced adverse events. To understand if and how the gut microbiome contributes to chemotherapy-induced adverse effects in ALL, we will transplant gut bacteria from patients impacted by chemotherapy-induced toxicities into germ-free mice and mechanistically decode the effect of gut commensals on these adverse effects.