Early intestinal microbial features are associated with CD4 T cell recovery after allogeneic hematopoietic transplant

Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2,067 stool samples and flow-cytometry data from 2,370 peripheral blood samples drawn from 894 allogeneic HCT patients, we have linked features of the early post-HCT microbiome with subsequent immune cell recovery. We examined lymphocyte recovery and microbiota features in recipients of both unmodified and CD34-selected allografts. We observed that fecal microbial diversity was an independent predictor of CD4 T cell count 3 months after HCT in recipients of a CD34-selected allograft, who are dependent on de novo lymphopoiesis for their immune recovery. In multivariate models using clinical factors and microbiota features, we consistently observed that increased fecal relative abundance of genus Staphylococcus during the early post-transplant period was associated with worse CD4 T cell recovery. Our observations suggest that the intestinal bacteria - or the factors they produce - can affect early lymphopoiesis and the homeostasis of allograft-derived T cells after transplantation.