Febrile Neutropenia Duration Is Associated with the Severity of Gut Microbiota Dysbiosis in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

SIMPLE SUMMARY: Febrile neutropenia is a common complication in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation. Its genesis is often attributed to infections; however, a specific cause frequently cannot be defined. We hypothesize that the composition of the intestinal flora may contribute to the genesis of the neutropenic fever. We analyzed the microbial composition of stool samples from pediatric patients from three European centers and assessed the relationship with the duration of the fever during neutropenia. We found that a more stable composition of the microbiota during the transplantation course is associated with a shorter duration of fever. Moreover, patients with a higher duration of fever presented higher levels of Collinsella, Megasphaera, Prevotella, Roseburia, Eggerthella and Akkermansia in the stool. ABSTRACT: Febrile neutropenia (FN) is a common complication in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Frequently, a precise cause cannot be identified, and many factors can contribute to its genesis. Gut microbiota (GM) has been recently linked to many transplant-related complications, and may also play a role in the pathogenesis of FN. Here, we conducted a longitudinal study in pediatric patients receiving HSCT from three centers in Europe profiling their GM during the transplant course, particularly at FN onset. We found that a more stable GM configuration over time is associated with a shorter duration of fever. Moreover, patients with longer lasting fever exhibited higher pre-HSCT levels of Collinsella, Megasphaera, Prevotella and Roseburia and increased proportions of Eggerthella and Akkermansia at the engraftment. These results suggest a possible association of the GM with the genesis and course of FN. Data seem consistent with previous reports on the relationship of a so-called “healthy” GM and the reduction of transplant complications. To our knowledge, this is the first report in the pediatric HSCT setting. Future studies are warranted to define the underling biological mechanisms and possible clinical implications.