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.