Abstract

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). In this pilot study, we examined the impact of GD on the gut microbiome composition and incidence of aGVHD in HCT patients.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).The two arms did not differ in the predefined primary outcome of Shannon diversity of the gut microbiome at two weeks post-HCT (Genus, p=0.8; Species, p=0.44) or aGVHD incidence (p=0.58). Immune reconstitution of T-cell and B-cell subsets was similar between groups. 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 Staphylococcus species.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 pathogens.ClinicalTrials.gov NCT02641236FUNDING. NIH, Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, Stanford MCHRI.

View details for DOI 10.1172/jci.insight.154344

View details for PubMedID 35239511