The Microbiome in Childhood Acute Lymphoblastic Leukemia

SIMPLE SUMMARY: The role of the microbiome for the development and treatment of acute lymphoblastic leukemia (ALL) is not well understood. The immune system and microbiota closely interact and perturbations have strong implications for ALL development and course of the treatment. Significant differences in the microbiome with reduced diversity have been observed already at the onset of disease and have potential implications for leukemogenesis. Furthermore, the regular chemotherapeutic treatment regimen severely perturbs the microbiome, being associated with severe side effects such as mucositis, systemic inflammation, or infections. Herein, we review the latest microbiome studies in pediatric ALL patients, as well as provide an overview of current and future options to modulate the microbiome to improve the treatment’s outcome or even prevent leukemia development. ABSTRACT: For almost 30 years, the term “holobiont” has referred to an ecological unit where a host (e.g., human) and all species living in or around it are considered together. The concept highlights the complex interactions between the host and the other species, which, if disturbed may lead to disease and premature aging. Specifically, the impact of microbiome alterations on the etiology of acute lymphoblastic leukemia (ALL) in children is not fully understood, but has been the focus of much research in recent years. In ALL patients, significant reductions in microbiome diversity are already observable at disease onset. It remains unclear whether such alterations at diagnosis are etiologically linked with leukemogenesis or simply due to immunological alteration preceding ALL onset. Regardless, all chemotherapeutic treatment regimens severely affect the microbiome, accompanied by severe side effects, including mucositis, systemic inflammation, and infection. In particular, dominance of Enterococcaceae is predictive of infections during chemotherapy. Long-term dysbiosis, like depletion of Faecalibacterium, has been observed in ALL survivors. Modulation of the microbiome (e.g., by fecal microbiota transplant, probiotics, or prebiotics) is currently being researched for potential protective effects. Herein, we review the latest microbiome studies in pediatric ALL patients.