Introduction
Improvements in treatment for childhood cancer patients have led to more than 80% of patients becoming long-term survivors [1], with more than 400,000 survivors of childhood cancer living in the United States [2]. However, among long-term survivors, the rates of chronic severe health conditions remain greatly elevated compared to those of the general population [2-4]. Metabolic syndrome and obesity occur commonly in long-term survivors and exacerbate other chronic health conditions [5-15]. Chronic inflammation has several mechanistic links to obesity and metabolic syndrome [16], and long-term survivors of pediatric malignancies show evidence of chronic inflammation [5,17,18]. How chronic inflammation is mechanistically related to long-term side effects in survivors is still poorly understood.
The microbiome is associated with multiple aspects of pediatric oncology [19]. Active treatment for cancer patients clearly alters the intestinal microbiome [20-22]; however, it is less clear if these changes persist many years after treatment. In otherwise healthy neonates and young children, treatment with antibiotics leads to long-term changes in the microbiome [23-25]. Antibiotic use in infancy is associated with an increased risk of obesity [26], and changes in the microbiome have been associated with several components of metabolic syndrome in the general population [27-29]. These findings have led some to propose that cancer treatment may lead to microbiome reconstitution with pro-inflammatory organisms that increase the risk for metabolic syndrome [8]. We hypothesized that long-term survivors of pediatric cancer and blood and marrow transplantation (BMT) would have reduced bacterial microbiome diversity compared to controls, and these findings would be associated with components of the metabolic syndrome and chronic inflammation. To test this hypothesis, and with the potential to generate new hypotheses, we performed a single-center, cross-sectional exploratory study examining the microbiome, clinical factors, and multiple biomarkers between long-term survivors and age, sex, and race matched controls.