Prebiotics to Augment the Gut Microbiome for Patients with Lymphoma or Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: The Primal Trial

Author

Christopher R. D'Angelo, University of Nebraska Medical CenterFollow

ORCID ID

0000-0001-8456-0889

Graduation Date

Fall 12-19-2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Matthew Lunning

Second Advisor

Peter Mannon

Third Advisor

Sarah Holstein

Abstract

In autologous hematopoietic stem cell transplantation (ASCT), post-transplant loss of microbiota taxa and diversity has been associated with adverse outcomes. We hypothesized that administration of resistant starch, a prebiotic, pre- and post-ASCT would prime the gut microbiome to preferentially support key microbiota members, maintain diversity, and reduce antibiotic exposure. We conducted the PRIMAL trial as a randomized, placebo-controlled, double-blind pilot study comparing resistant potato starch (RS) with a placebo (maltodextrin). The primary endpoints were feasibility and impact on gut microbiome diversity. RS was well tolerated at all time points, meeting the prespecified feasibility cutoffs: over 70% of subjects received 80% of the intended doses pre-transplant, and over 70% completed RS doses on over 50% of post-transplant days. Differential abundance calculations identified statistically significant improvements in known RS-degraders and short-chain fatty acid producers, including Ruminococcus and Bifidobacterium. IV antibiotic exposure was lower in the RS cohort than in the placebo (43% vs 58%), but the difference was not statistically significant (p = 0.33). There were no significant improvements in alpha diversity at the tested pre- and post-transplant time points compared with placebo. A comparison of IV antibiotic exposure between the RS cohort and a historical cohort of lymphoma patients undergoing ASCT between 2012 and 2022 showed a statistically significant reduction (43% vs 82%, p < 0.001). We conclude that RS is feasible, well-tolerated, and produces significant increases in short-chain fatty acid producers post-transplant, with the potential to reduce IV antibiotic exposure. These findings support continued development of prebiotic approaches to target the gut microbiome as a therapeutic strategy to improve outcomes in patients with hematologic malignancies receiving cellular therapy.

Comments

2025 Copyright, the authors

Recommended Citation

D'Angelo, Christopher R., "Prebiotics to Augment the Gut Microbiome for Patients with Lymphoma or Multiple Myeloma Undergoing Autologous Hematopoietic Stem Cell Transplantation: The Primal Trial" (2025). Theses & Dissertations. 999.
https://digitalcommons.unmc.edu/etd/999