Gut microbiome composition and plasma cytokines in acute leukaemia in relation to chemotherapy

Abstract

Abstract Background: The gut microbiome and cytokines are involved in maintaining immune homeostasis and may influence the prognosis and complications experienced by acute leukaemia (AL) patients receiving chemotherapy. Methodology: This longitudinal study analysed blood and stool samples from AL patients (≥ 18 years, scheduled for intensive chemotherapy) in two groups: no prior exposure to chemotherapy (CNE) and prior chemotherapy exposure (CE). Samples were collected at three time points: pre-chemotherapy (T0), an on-treatment time point (T1), and approximately two weeks post-chemotherapy (T2). The gut microbiome was assessed using 16S rRNA sequencing, while cytokines (IL-5, IL-10, IL-17, TNF-a, IFN-g, TGF-b) and gut permeability markers (I-FABP and zonulin) were quantified using immunoassays. Results: A total of 33 AL patients (CNE=21; CE=12; median age=51 years) were recruited and analysed. In unadjusted analyses, a significant decrease in gut microbiome alpha diversity was observed at T2 compared to T0 ( p <0.05), consistent with post-chemotherapy dysbiosis. Beta diversity showed no significant differences across time points or subgroups. Numerical increases in genera such as Enterococcus and Escherichia-Shigella were noted at T1. In assessments of gut integrity, a significant decrease in I-FABP ( p =0.023) and zonulin ( p =0.022) were observed at T2 compared to T0. Cytokine profiling revealed no significant changes in TNF-α or IFN-γ. IL-5 levels increased at T1 and T2 ( p <0.05), TGF-β decreased from T0 to T1 ( p <0.05), and IL-17 rose from T0 to T1 in CNE patients ( p <0.05) (all in unadjusted analyses). Conclusion: These findings are consistent with peri-chemotherapy shifts in gut microbiome and plasma cytokine. Confirmation in larger cohorts using repeated-measures analyses with covariate adjustment is warranted before drawing clinical inferences.