Role of intestinal microbiota in transplantation outcomes

Abstract

While allogeneic hematopoietic stem cell transplantations have a curative potential, infections and graft-versus-host disease remain significant problems. The intestinal microbiota can influence responses to cancer chemotherapy and the role of the microbiota in affecting allogeneic hematopoietic stem cell transplantation outcomes is increasingly appreciated. The following paper discusses the most recent developments in this area.

Trial registration: ClinicalTrials.gov NCT02269150.

Keywords: Allo-HSCT; Bacteremia; Diversity; Intestinal microbiota; Metronidazole; Microbial dominance; Mortality; Survival.

Conflict of interest statement

Conflict of interest

Eric G. Pamer: No relevant financial relationships with any commercial interest.

Copyright © 2015 Elsevier Ltd. All rights reserved.

Figures

Figure 1

VRE dominates the intestinal microbiota in humans prior to invading the bloodstream [11]. Stool samples from 5 patients (A–E) were studied prior to and during the transplant period. Each bar on the graph depicts the microbiota of 1 stool sample. Days the samples were collected relative to the day of transplant are indicated along the x-axis. The red horizontal bars indicate the timing of vancomycin-resistant Enterococcus bloodstream infections in patients A and B. Republished with permission of Journal of Clinical Investigation, from Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans, Ubeda C et al, volume 120, number 12, copyright 2010; permission conveyed through Copyright Clearance Center, Inc.

Figure 2

Risk of intestinal domination of the microbiota increases over time following allo-HSCT [12]. This Kaplan-Meier plot shows intestinal domination by Enteroccocus (top), Streptococcus (middle), and Proteobacteria (bottom) at various times throughout the transplant observation period. Republished by permission of Oxford University Press and the Infectious Diseases Society of America. Taur Y, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:905–914.

Figure 3

Intestinal microbiota diversity decreases following allo-HSCT [12]. A microbiota diversity trend, solid black line, was calculated for each fecal specimen of each patient during the transplant period using the Shannon diversity index. The gray area indicates the 95% confidence interval. Intestinal microbiota diversity decreased after allo-HSCT (Day 0). Republished by permission of Oxford University Press and the Infectious Diseases Society of America. Taur Y, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:905–914.

Figure 4

Loss of microbiota diversity following allo-HSCT is variable [12]. The microbiota diversity of 3 patients following allo-HSCT is depicted here. The vertical bars represent the microbial composition of a single fecal sample, and the horizontal bars indicate antibiotics administered concurrently. As can be seen, the diversity is variable from patient to patient. Republished by permission of Oxford University Press and the Infectious Diseases Society of America. Taur Y, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:905–914.

Figure 4

Loss of microbiota diversity following allo-HSCT is variable [12]. The microbiota diversity of 3 patients following allo-HSCT is depicted here. The vertical bars represent the microbial composition of a single fecal sample, and the horizontal bars indicate antibiotics administered concurrently. As can be seen, the diversity is variable from patient to patient. Republished by permission of Oxford University Press and the Infectious Diseases Society of America. Taur Y, et al. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis 2012;55:905–914.

Figure 5

After transplant engraftment: Intestinal microbial diversity correlates with survival [13]. This research was originally published in Blood. Taur Y, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 2014;124:1174–1182. © the American Society of Hematology.

Figure 6

Transplant-related mortality is markedly reduced in patients with a diverse microbiota following engraftment [13]. This research was originally published in Blood. Taur Y, et al. The effects of intestinal tract bacterial diversity on mortality following allogeneic hematopoietic stem cell transplantation. Blood 2014;124:1174–1182. © the American Society of Hematology.