Enteral versus parenteral nutrition in auto-HCT: a randomized controlled trial on clinical outcomes and gut microbiome dynamics

Disruption of the gut microbiome is a common consequence of chemotherapy, linked with detrimental treatment outcomes (e.g. sepsis), especially in haematopoietic stem cell transplant (HCT) recipients. Preclinical data suggest that enteral nutrition (EN) is superior to parenteral nutrition (TPN), minimising gut atrophy and promoting eubiosis; yet, TPN continues to be used. Here, we evaluated the clinical effects of EN and TPN in autologous HCT recipients and their influence on gut microbiome dynamics. Despite efforts to optimise delivery, EN was poorly tolerated and ultimately proved unfeasible. As such, we turned our attention to analysing microbial dynamics in our study cohort and confirmed preclinical reports that epithelial apoptosis drives gut microbiome disruption. Machine learning models predicted microbial composition by tracking plasma citrulline trajectories, a biomarker of enterocyte mass. These findings suggest that (i) monitoring citrulline may be able to identify patients at risk of potentially lethal HCT complications associated with gut microbiome disruption, and that (ii) preserving epithelial integrity could support microbial resilience by minimising the production of caspase-dependent metabolites. Dutch Trial Register: NL4069. Data registered: 19-11-2013. www.trialregister.nl.