The Microbiome and Pediatric Transplantation

Abstract

The microbial communities that inhabit our bodies have been increasingly linked to host physiology and pathophysiology. This microbiome, through its role in colonization resistance, influences the risk of infections after transplantation, including those caused by multidrug-resistant organisms. In addition, through both direct interactions with the host immune system and via the production of metabolites that impact local and systemic immunity, the microbiome plays an important role in the establishment of immune tolerance after transplantation, and conversely, in the development of graft-versus-host disease and graft rejection. This review offers a comprehensive overview of the evidence for the role of the microbiome in hematopoietic cell and solid organ transplant complications, drivers of microbiome shift during transplantation, and the potential of microbiome-based therapies to improve pediatric transplantation outcomes.

Keywords: antibiotic resistance; biotherapeutics; gut microbiota; hematopoietic stem cell transplant; solid organ transplant.

Figure 1.

Host factors and exposures that influence microbiome colonization resistance and host infection susceptibility. Two microbial communities are shown representing opposite ends of the spectrum of microbiome diversity, stability, colonization resistance, and host susceptibility to infection. Compared with the microbiome shown at the bottom of the figure, the microbiome at the top of the figure has higher diversity in that it contains more species and these species have similar abundances; such a state is also generally associated with higher stability (more resiliency to external perturbations), the ability to more effectively resist colonization by potential pathogens, and lower susceptibility to infections.

Figure 2.

Key drivers of microbiome injury and microbiome–host interactions that influence outcomes after transplantation. In health (shown on the left), diverse gut microbes and microbial metabolites maintain epithelial barrier integrity, resist pathogen expansion, and promote host immune recovery and tolerance. During transplantation (shown on the right), dietary changes, antibiotics, and immunosuppressive medications alter the microbiome, leading to the loss of putatively beneficial bacteria and the expansion of potential pathogens that produce harmful metabolites that promote inflammation and alter the intestinal microenvironment. These changes leave the host susceptible to bacterial translocation and initiate an inflammatory cascade that can result in adverse outcomes of transplantation such as GVHD and graft failure. GVHD, graft-versus-host disease; SCFA, short-chain fatty acid; TLR, Toll-like receptor.

Figure 3.

Microbiome-based interventions in development or under investigation for use in transplant recipients. Strategies that seek to directly alter the microbiome include prebiotics (nonviable substances that promote the growth of beneficial microbes), probiotics (live microorganisms that confer a potential health benefit), bacteriophages that enable targeted elimination of harmful bacteria, transfer of entire gut microbial communities through fecal microbiota transplantation, and administration of microbial consortia containing multiple live bacterial strains. Other strategies such as dietary modifications and selection of specific antibiotics for prophylaxis or treatment indirectly modify the microbiome with the potential to influence transplantation outcomes. Created with Biorender.com.