Temporal changes in gut microbiota profile in children with acute lymphoblastic leukemia prior to commencement-, during-, and post-cessation of chemotherapy

Abstract

Background: Alteration in gut microbiota has been recently linked with childhood leukemia and the use of chemotherapy. Whether the perturbed microbiota community is restored after disease remission and cessation of cancer treatment has not been evaluated. This study examines the chronological changes of gut microbiota in children with acute lymphoblastic leukemia (ALL) prior to the start-, during-, and following cessation of chemotherapy. Methodology: We conducted a longitudinal observational study in gut microbiota profile in a group of paediatric patients diagnosed with ALL using 16 s ribosomal RNA sequencing and compared these patients' microbiota pattern with age and ethnicity-matched healthy children. Temporal changes of gut microbiota in these patients with ALL were also examined at different time-points in relation to chemotherapy. Results: Prior to commencement of chemotherapy, gut microbiota in children with ALL had larger inter-individual variability compared to healthy controls and was enriched with bacteria belonging to Bacteroidetes phylum and Bacteroides genus. The relative abundance of Bacteroides decreased upon commencement of chemotherapy. Restitution of gut microbiota composition to resemble that of healthy controls occurred after cessation of chemotherapy. However, the microbiota composition (beta diversity) remained distinctive and a few bacteria were different in abundance among the patients with ALL compared to controls despite completion of chemotherapy and presumed restoration of normal health. Conclusion: Our findings in this pilot study is the first to suggest that gut microbiota profile in children with ALL remains marginally different from healthy controls even after cessation of chemotherapy. These persistent microbiota changes may have a role in the long-term wellbeing in childhood cancer survivors but the impact of these changes in subsequent health perturbations in these survivors remain unexplored.

Bidirectional interaction between intestinal microbiome and cancer: opportunities for therapeutic interventions

“…Fecal microbiota in ALL patients showed lower microbial diversity [38]. They were enriched in Enterococcaceae, Porphyromonadaceae, and Bacteroidetes (mainly B. fragilis), and depleted in Blautia, Erysipelotrichiales, Lachnospiraceae and Clostridiales members [39,40]. Abundance of Staphylococcaceae and Streptococcaceae have also been reported in pediatric ALL and adult AML [41,42].…”

Cognitive complications of cancer and cancer-related treatments – Novel paradigms

“…Intestinal microbes decreased in the stool samples of the ALL group post-chemotherapy completion by 29.6% compared to the controls. MTX-induced changes in the gut microbiota composition were evident one-week posttreatment completion and at least 9 months after cessation of chemotherapy in a separate study of ALL survivors 116 . Additional studies suggest that chemotherapy treatment results in reduced gut microbiota diversity, leading to mucositis, inflammation, and long-term microbiota dysbiosis 117,118 .…”

The microbiome in pediatric oncology

“…27,28 Likewise, patients undergoing HCT or pediatric patients undergoing conventional chemotherapy also have demonstrated reductions in microbiome diversity with antibiotic exposure. 6,29,30 How these changes affect the outcomes of treatment is an area of active investigation. Non-antibiotic exposures during cancer treatment and HCT also may lead to a loss of microbiome diversity.…”

“…Antibiotic administration clearly plays a role in gut dysbiosis in the general population 27,28 . Likewise, patients undergoing HCT or pediatric patients undergoing conventional chemotherapy also have demonstrated reductions in microbiome diversity with antibiotic exposure 6,29,30 . How these changes affect the outcomes of treatment is an area of active investigation.…”