Distinct functional and compositional properties in the gut microbiome of children with acute lymphoblastic leukaemia identified by shotgun metagenomics.

Acute lymphoblastic leukaemia (ALL) represents the most common childhood malignancy, and emerging evidence underscores the impact of the gut microbiome (GM) on its pathogenesis. In this study, we used shotgun metagenomics to investigate the GM of 30 ALL patients at diagnosis-19 with B-ALL and 11 with T-ALL-and compared them to 176 healthy controls (HCs). When considered as a single ALL group versus HCs, clear compositional differences emerged: ALL patients exhibited higher relative abundances of Enterococcus faecium, oral commensals such as Rothia dentocariosa, and multiple opportunistic species, whereas HCs were enriched in short-chain fatty acid producers like Anaerostipes hadrus and Intestinibacter bartlettii. Functionally, the ALL GM relied more on protein and amino acid catabolism, while HCs possessed enhanced pathways for carbohydrate and folate metabolism. These findings broadly align with 16S rRNA-based analyses from previous publications, though some discrepancies highlight differences in technique-driven resolution. In contrast, comparing the two major molecular phenotypes-B-ALL and T-ALL-revealed only minimal taxonomic and functional differences, primarily confined to BAs metabolism pathways. Overall, our results indicate that children with ALL at the time of diagnosis already display a dysbiotic signature, bolstering the notion that a disturbance in GM development during childhood may be linked to the multistep pathogenesis model of ALL.