Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors

Abstract

Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient's pre-conditioning microbiota nor the influence of the transplant donor's microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors. On average, recipients had lower fecal bacterial diversity (P=0.0002) and different phylogenetic membership (UniFrac P=0.001) than the healthy transplant donors. Recipients with lower phylogenetic diversity had higher overall mortality rates (hazard ratio=0.37, P=0.008), but no statistically significant difference in agGvHD risk. In contrast, high bacterial donor diversity was associated with decreased agGvHD risk (odds ratio=0.12, P=0.038). Further investigation is warranted as to whether selection of hematopoietic stem cell transplant donors with high gut microbiota diversity and/or other specific compositional attributes may reduce agGvHD incidence, and by what mechanisms.