Shotgun Metagenomics Identify Unique Changes of the Intestinal Microbiome in Pediatric Survivors of Acute Lymphoblastic Leukemia.

Abstract

BACKGROUND: Intestinal microbiota plays an important role in human health and metabolism. Microbial dysbiosis has been observed in various chronic conditions, many of which are late effects of leukemia treatment. We previously observed significant differences in the gut microbiome of pediatric ALL survivors compared to healthy sibling controls. Shotgun metagenomic analyses were completed to better characterize the durability and metabolic implication of these changes. PROCEDURE: Shotgun metagenomic sequencing was completed on DNA extracted from stool samples obtained from nine survivors of childhood acute lymphoblastic leukemia (ALL) and 10 healthy sibling controls. RESULTS: Beta diversity (dissimilarity between samples) was significant with survivors' microbiomes becoming more similar to siblings further from treatment. The functional potential of gluconate-5-dehydrogenase enzyme (Ga5DH) decreased significantly with time from treatment. Relative abundance of Faecalibacterium prausnitzii was identified as the major contributor to differential Ga5DH expression within subjects. CONCLUSIONS: Time from treatment has a significant effect on functional microbial recovery in ALL. Increased time from chemotherapy corresponds to microbiomes becoming more similar to sibling controls in select dyads. More significant differences were noted in patients closer to treatment. Additional, prospective studies will focus on deeper characterization of these findings and further investigate the functional role of Ga5DH in ALL survivors.