Distinct Functional and Compositional properties in the Gut Microbiome of Children with Acute Lymphoblastic Leukemia: A Shotgun Metagenomics Study

This project investigates the gut microbiome (GM) of children diagnosed with acute lymphoblastic leukemia (ALL), the most common childhood malignancy, and compares their microbial profiles to those of healthy controls (HCs). We performed shotgun metagenomic sequencing on fecal samples from 30 pediatric ALL patients (19 with B-ALL and 11 with T-ALL) at diagnosis, alongside data from 176 HCs. Our analyses revealed distinct compositional and functional shifts in the ALL microbiome, including higher relative abundances of Enterococcus faecium and oral commensals such as Rothia dentocariosa, as well as a greater reliance on protein and amino acid catabolism pathways. In contrast, HCs were enriched in short-chain fatty acid producers like Anaerostipes hadrus and Intestinibacter bartlettii and displayed enhanced carbohydrate and folate metabolic pathways. Minimal differences were noted between B-ALL and T-ALL subtypes, confined primarily to bile acid metabolism. Overall, these findings suggest that a dysbiotic GM signature is present at ALL diagnosis, reinforcing the hypothesis that early-life gut microbiome disturbances may be linked to leukemia pathogenesis.