Abstract: Background. Gut decontamination (GD) can decrease the incidence and severity of acute graft-versus-host-disease (aGVHD) in murine models of allogeneic hematopoietic cell transplantation (HCT). Several HCT centers standardly practice GD with different antibiotic regimens. In this pilot study, we examined the impact of GD on the gut microbiome composition and incidence of aGVHD in HCT patients. Methods. We randomized 20 pediatric patients undergoing allogeneic HCT to receive (GD) or not receive (no-GD) oral vancomycin-polymyxin B from day -5 through neutrophil engraftment. We evaluated shotgun metagenomic sequencing of serial stool samples to compare the composition and diversity of the gut microbiome between study arms. We assessed clinical outcomes in the 2 arms and performed strain-specific analyses of pathogens that caused bloodstream infections (BSI). Results. The two arms did not differ in Shannon diversity of the gut microbiota at two weeks post-HCT (Genus, p=0.8; Species, p=0.44) or aGVHD incidence (p=0.58). Immune reconstitution of T-cell subsets was similar, but absolute CD19+ B-cell counts were higher in the GD arm at 12 months post-HCT (p=0.02). Five patients in the no-GD arm had eight BSI episodes vs one episode in the GD arm (p=0.09). The BSI-causing pathogens were traceable to the gut in seven of eight BSI episodes in the no-GD arm, including the genus Staphylococcus. Conclusions. While GD did not differentially impact Shannon diversity or clinical outcomes, our findings suggest that GD may protect against gut-derived BSI in HCT patients by decreasing the prevalence or abundance of gut microbial pathogens. Trial Registration. ClinicalTrials.gov NCT02641236 Funding. Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, Stanford MCHRI, NIH-R01-AI143757, R01-AI148623, S100D023452, 1S10OD02014101, T32-DK098132.

Journal Link: 10.1101/2021.12.16.21267940 Journal Link: Publisher Website Journal Link: Download PDF Journal Link: Google Scholar