Changes in the Gut Microbial Diversity and Its Correlation with the Clinical Outcome in Children with Acute Myeloid Leukemia (AML) Receiving Induction Chemotherapy

Introduction Febrile neutropenia (FN) in patients with AML is associated with iatrogenic damage to the gut microbiota. Intensive chemotherapy also impairs gut barrier integrity, facilitating bacterial translocation and increasing the risk of bloodstream infection.Objectives: Our study aimed to describe the microbiological profile and microbiome changes in newly diagnosed AML children during the induction period and its impact on the clinical outcome. Patients and methods: This is a prospective study conducted at Children's cancer hospital in Egypt, studying 29 newly diagnosed AML patients aged 0-18 years during induction chemotherapy. The study was designated to compare the changes in gut microbiota at 3-time points: before induction chemotherapy D0, D7, and D21 from the beginning of induction chemotherapy. Two samples (rectal swabs or stool samples) were collected for each patient at three-time points; One swab was used for the microbiology analysis, and the other was stored at −20 °C for 16S rRNA sequencing. The Friedman test was used to assess for changes in alpha diversity from Day 0 to Day 7 to Day 21 samples. Microbial DNA was extracted from stool samples, and sequencing of the V4 region of the bacterial 16S rRNA genes was performed using an Illumina MiSeq platform. Alpha microbial diversity was measured by the Shannon Index. The Kruskal Wallis one-way variance test was performed to assess for changes in alpha diversity from baseline to day 7 to d21 samples. DESeq2 was used to identify differentially abundant bacteria at 3-time points. The samples were grouped into two groups, patients who did not acquire MDRO - and were treated as a control and patients who acquired MDRO during their hospital stay. MDRO biomarkers were identified using the online tool Galaxy lefse at the Genus level. Results Chemotherapy significantly decreases the Microbial richness of the Gut microbiome. Regarding relative abundance at phyla and genera level: Actinobacter is the most abundant before starting chemotherapy, Proteobacteria and Firmicutes are highly abundant on day 7 and on day 21. Verrucomicrobacteria increases on day 7 and disappears on day 21. Conclusion Gut microbial diversity declines in patients receiving intensive induction chemotherapy for AMLduring Induction Chemotherapy, even without antibacterial therapy. Additional study of the impact of the gut microbiome on outcomes in patients with AML is warranted to correlaate it with the clinical outcome.

No relevant conflicts of interest to declare.