Journal Article

The eukaryotic gut virome in hematopoietic stem cell transplantation: new clues in enteric graft-versus-host disease

Simon, François, Mercier-Delarue, Séverine, Samayoa, Erik, Chiu, Charles Y, Robin, Marie, Resche-Rigon, Matthieu, Rousseau, Clotilde, Legoff, Jérôme, Bouquet, Jerome, Piron, Prescillia, Kapel, Nathalie, Socié, Gérard, Naccache, Samia N, Federman, Scot

2017

Overview

Charles Chiu and colleagues analyze the gut viromes of recipients of hematopoietic stem cell transplantation and identify characteristics associated with the severity of graft-versus-host disease in the gut. Much attention has been focused on the role of the bacterial microbiome in human health, but the virome is understudied. Although previously investigated in individuals with inflammatory bowel diseases or solid-organ transplants 1 , 2 , virome dynamics in allogeneic hematopoietic stem cell transplantation (HSCT) and enteric graft-versus-host disease (GVHD) remain unexplored. Here we characterize the longitudinal gut virome in 44 recipients of HSCT using metagenomics. A viral 'bloom' was identified, and significant increases were demonstrated in the overall proportion of vertebrate viral sequences following transplantation ( P = 0.02). Increases in both the rates of detection ( P < 0.0001) and number of sequences ( P = 0.047) of persistent DNA viruses (anelloviruses, herpesviruses, papillomaviruses and polyomaviruses) over time were observed in individuals with enteric GVHD relative to those without, a finding accompanied by a reduced phage richness ( P = 0.01). Picobirnaviruses were detected in 18 individuals (40.9%), more frequently before or within a week after transplant than at later time points ( P = 0.008). In a time-dependent Cox proportional-hazards model, picobirnaviruses were predictive of the occurrence of severe enteric GVHD (hazard ratio, 2.66; 95% confidence interval (CI) = 1.46–4.86; P = 0.001), and correlated with higher fecal levels of two GVHD severity markers, calprotectin and α1-antitrypsin. These results reveal a progressive expansion of vertebrate viral infections over time following HSCT, and they suggest an unexpected association of picobirnaviruses with early post-transplant GVHD.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 38/23 / 38/90 / 38/91 / 45 / 631/326/596/2097 / 692/308/53/2421 / 692/699/1503/1581 / 692/699/249/1529 / 692/699/255/2514 / a1-antitrypsin / Adolescent / Adult / Aged / alpha 1-Antitrypsin - metabolism / Anelloviridae - genetics / Anelloviridae - immunology / Bacteria / Biomedicine / Cancer Research / Care and treatment / Confidence intervals / Deoxyribonucleic acid / Disease / DNA / DNA viruses / DNA, Viral - analysis / Eukaryotes / Feces - chemistry / Female / Gastrointestinal diseases / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - immunology / Gene sequencing / Graft vs Host Disease - immunology / Graft-versus-host reaction / Hazards / Hematopoietic Stem Cell Transplantation / Herpesviridae - genetics / Herpesviridae - immunology / Humans / Infectious Diseases / Inflammatory bowel diseases / Intestinal Diseases - immunology / Intestine / Intestines - virology / letter / Leukocyte L1 Antigen Complex - metabolism / Male / Metabolic Diseases / Metagenomics / Microbiota (Symbiotic organisms) / Middle Aged / Molecular Medicine / Neurosciences / Nucleotide sequence / Papillomaviridae / Papillomaviridae - genetics / Papillomaviridae - immunology / Patient outcomes / Phages / Physiological aspects / Picobirnavirus - genetics / Picobirnavirus - immunology / Plastic surgery / Polyomaviridae - genetics / Polyomaviridae - immunology / Proportional Hazards Models / Risk Factors / Severity of Illness Index / Stem cell transplantation / Stem cells / Transplantation / Transplantation, Homologous / Transplants / Transplants & implants / Vertebrates / Young Adult