Microbiome analysis in patients with antibiotic associated neutropenia compared to healthy controls

Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In our multi-center study, patients with infections requiring hospital admission and anticipated treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at time neutropenia presented. In this cohort of patients receiving antibiotics, we identified 10 patients who developed neutropenia and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic, but ICU stay and length of IV therapy were associated with neutropenia. Stool metabolomes assessed by untargeted profiling generally overlapped between groups; nonetheless, we noted that several metabolites were depleted exclusively in patients with neutropenia. Reduced intestinal microbiome richness and depletion of the Lachnospiraceae family correlated with neutropenia (p=0.027 & 0.043 respectively). Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and highlights taxa and metabolites of interest likely to contribute to microbiota-sustained hematopoiesis.