Gut Microbiome Sysbiosis in Childhood Acute Lymphoblastic Leukemia (ALL) Patients
An estimated 15,000 children under the age of 19 years are diagnosed with leukemia, lymphoma and other tumors in the USA every year. Acute Lymphoblastic Leukemia (ALL) accounts for 75% of all childhood leukemias. Most of these children and adolescents will undergo chemotherapy as part of their treatment plan and subsequently, their immediate and long-term health can be severely compromised because of repeated administration of cytotoxic drugs. Administration of chemotherapy agents and supportive care in the form of prophylactic antibiotics can disrupt the ecological balance of the gastrointestinal (GI) microbiome and cause side effects that severely compromise the quality of life.
In this series of studies, we have profiled the gut microbiome dynamics and blood plasma proteomics of pediatric and adolescent patients with ALL at diagnosis and during the chemotherapy treatment course. A total of 249 fecal samples are analyzed in this study. 16S rDNA gene sequencing gave an average of 22,334 sequences per sample. We observed that the microbiome richness of the patient group is significantly lower than that of the control group at diagnosis and during the chemotherapy regimen. During chemotherapy, the gut microbiome diversity and richness remains low. Interestingly, the mucolytic gram-positive anaerobic bacteria Ruminococcus gnavus and Ruminococcus torques were significantly increased during the chemotherapy regimen, and even after one-year post-chemotherapy. This dysbiosis may contribute to the development of clinically evaluated gastrointestinal mucositis in immunocompromised children after chemotherapy. Analysis of the global plasma proteome during chemotherapy revealed proteins with roles in the acute-phase response, the innate immune responses, lipid homeostasis, and hypogonadism as differentially abundant in response to chemotherapy.
Funding for this project provided through Hyundai Hope On Wheels and the J. Craig Venter Institute.