Gut microbial composition difference between pediatric ALL survivors and siblings

Abstract

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer with high cure rates leading to rising numbers of long-term survivors. Adult survivors of childhood ALL are at increased risk of obesity, cardiovascular disease, and other chronic illnesses. We hypothesize that ALL therapy is associated with long-term gut microbiome alterations that contribute to predisposition to chronic medical conditions. We conducted a pilot study to test whether differences can be detected between stool microbiota of pediatric ALL survivors and their siblings. Stool samples were collected from 38 individuals under age 19 who were at least 1 year after completion of therapy for ALL. Stool samples collected from 16 healthy siblings served as controls. 16S ribosomal RNA gene sequencing was performed on the stool samples. Comparing microbiota of survivors to sibling controls, no statistically significant differences were found in alpha or beta diversity. However, among the top 10 operational taxonomic units (OTUs) from component 1 in sparse partial least squares discriminant analysis (sPLS-DA) with different relative abundance in survivors versus siblings, OTUs mapping to the genus Faecalibacterium were depleted in survivors. Differences in gut microbial composition were found between pediatric survivors of childhood ALL and their siblings. Specifically, the protective Faecalibacterium is depleted in survivors, which is reminiscent of gut microbiota alteration found in adult survivors of childhood ALL and reported in obesity, suggesting that microbiota alterations in pediatric ALL survivors start in childhood and may play a role in predisposition to chronic illness in later years of survivorship.

Keywords:

• Acute lymphoblastic leukemia
• ALL survivors
• Faecalibacterium
• microbiome
• stool microbiota

Acknowledgements

We thank the PSV Long Term Follow Up team for access to patient roster and are grateful to the off therapy ALL patients and their families for donating samples to this research project. We gratefully acknowledge the support of research activities by Inova Children’s Hospital and the Pediatric Specialists of Virginia Philanthropy Fund, which generously provided gift cards for the study participants.

Conflict of interest

The authors have no conflicts of interest to disclose.

Additional information

Funding

This project was supported by a Pilot Project Grant from the Inova Translational Medicine Institute (Yang) and a Research Seed Grant from the Inova Research Council (Yang). Research reported in this publication was also supported in part by the National Institute of Child Health and Human Development under Award Number K23HD099240 (Hourigan). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.