Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation
Christopher J. Severyn, Benjamin A. Siranosian, Sandra Tian-Jiao Kong, Angel Moreno, Michelle M. Li, Nan Chen, Christine N. Duncan, Steven P. Margossian, Leslie E. Lehmann, Shan Sun, Tessa M. Andermann, Olga Birbrayer, Sophie Silverstein, Carol G. Reynolds, Soomin Kim, Niaz Banaei, Jerome Ritz, Anthony A. Fodor, Wendy B. London, Ami S. Bhatt, Jennifer S. Whangbo
Christopher J. Severyn, Benjamin A. Siranosian, Sandra Tian-Jiao Kong, Angel Moreno, Michelle M. Li, Nan Chen, Christine N. Duncan, Steven P. Margossian, Leslie E. Lehmann, Shan Sun, Tessa M. Andermann, Olga Birbrayer, Sophie Silverstein, Carol G. Reynolds, Soomin Kim, Niaz Banaei, Jerome Ritz, Anthony A. Fodor, Wendy B. London, Ami S. Bhatt, Jennifer S. Whangbo
View: Text | PDF
Clinical Research and Public Health Hematology Infectious disease

Microbiota dynamics in a randomized trial of gut decontamination during allogeneic hematopoietic cell transplantation

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). In this pilot study, we examined the impact of GD on gut microbiome composition and the incidence of aGVHD in HCT patients.METHODS We randomized 20 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 2 arms did not differ in the predefined primary outcome of Shannon diversity of the gut microbiome at 2 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 8 BSI episodes versus 1 episode in the GD arm (P = 0.09). The BSI-causing pathogens were traceable to the gut in 7 of 8 BSI episodes in the no-GD arm, including Staphylococcus species.CONCLUSION While GD did not differentially affect 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.TRIAL REGISTRATION ClinicalTrials.gov NCT02641236.FUNDING NIH, Damon Runyon Cancer Research Foundation, V Foundation, Sloan Foundation, Emerson Collective, and Stanford Maternal & Child Health Research Institute.

Authors

Christopher J. Severyn, Benjamin A. Siranosian, Sandra Tian-Jiao Kong, Angel Moreno, Michelle M. Li, Nan Chen, Christine N. Duncan, Steven P. Margossian, Leslie E. Lehmann, Shan Sun, Tessa M. Andermann, Olga Birbrayer, Sophie Silverstein, Carol G. Reynolds, Soomin Kim, Niaz Banaei, Jerome Ritz, Anthony A. Fodor, Wendy B. London, Ami S. Bhatt, Jennifer S. Whangbo

×

Figure 6

Bacterial abundance in the gut around the time of BSI.

Options: View larger image (or click on image) Download as PowerPoint
Bacterial abundance in the gut around the time of BSI. Multiple pathogen...
Multiple pathogens are present in the gut around the time of the BSI. Days relative to the course of the transplant shown on the x axis (from top to bottom on the y axis), antibiotic administration, α (Shannon) diversity, relative abundance of microbes in the stool samples at the genus taxonomic level (with organisms listed by color according to the key at the lower left), and relative abundance in the gut of the BSI-causing organism with the date of the BSI shown as an asterisk (*). Note: y axis is a different scale between abundance plots for focused organisms found in the BSI. (A) Patient C04 had 2 Staphylococcus aureus BSIs 89 days apart (day +5 and day +94) and a Klebsiella oxytoca BSI on day +18. (B) E. coli BSI on day +8 in patient C10. (C) Staphylococcus epidermidis BSI on day +23 in patient C20. (D) Patient C22 received 2 transplants and had low abundance of Rothia dentrocariosa in the gut during the first transplant; Rothia was not detectable in the gut after day +15 of the first transplant, with a Rothia BSI on day +6 of the second transplant (day +85 relative to the first transplant). An Enterococcus faecium BSI occurred on day +20 of the second transplant (day +99 relative to the first transplant). Antifungal and antiviral medications are shown in Supplemental Figure 13. Information on patients C03 and C11 may be found in Supplemental Figure 11. Azithro, azithromycin; Cipro, ciprofloxacin; Clinda, clindamycin; Levo, levofloxacin; Mero, meropenem; PipTazo, piperacillin/tazobactam; TMP/SMX, trimethoprim/sulfamethoxazole (cotrimoxazole).