TY - JOUR
T1 - Enteral versus parenteral nutrition in auto-HCT
T2 - a randomized controlled trial on clinical outcomes and gut microbiome dynamics
AU - Wardill, Hannah R.
AU - van Groningen, Lenneke F.J.
AU - Dorraki, Mohsen
AU - Molendijk, Eva B.D.
AU - Kalter, Doris
AU - Da Silva Ferreira, Ana Rita
AU - Kurilshikov, Alexander
AU - Ryan, Feargal J.
AU - Verjans, Johan W.
AU - Harmsen, Hermie J.M.
AU - Tissing, Wim J.E.
AU - van der Velden, Walter J.F.M.
AU - Blijlevens, Nicole M.A.
PY - 2025/10
Y1 - 2025/10
N2 - 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
AB - 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
KW - Apoptosis
KW - Citrulline
KW - Gastrointestinal mucositis
KW - Gut microbiome
KW - Haematopoietic cell transplantation
KW - HCT
KW - Nutrition
UR - http://www.scopus.com/inward/record.url?scp=105016628811&partnerID=8YFLogxK
U2 - 10.1007/s00520-025-09882-z
DO - 10.1007/s00520-025-09882-z
M3 - Article
C2 - 40971058
AN - SCOPUS:105016628811
SN - 0941-4355
VL - 33
JO - Supportive Care in Cancer
JF - Supportive Care in Cancer
IS - 10
M1 - 865
ER -