Early intestinal microbial features are associated with CD4 T-cell recovery after allogeneic hematopoietic transplant
Oriana Miltiadous, Nicholas R. Waters, Hana Andrlová, Anqi Dai, Chi L. Nguyen, Marina Burgos da Silva, Sarah Lindner, John Slingerland, Paul Giardina, Annelie Clurman, Gabriel K. Armijo, Antonio L. C. Gomes, Madhavi Lakkaraja, Peter Maslak, Michael Scordo, Roni Shouval, Anna Staffas, Richard O’Reilly, Ying Taur, Susan Prockop, Jaap Jan Boelens, Sergio Giralt, Miguel-Angel Perales, Sean M. Devlin, Jonathan U. Peled, Kate A. Markey, Marcel R. M. van den Brink
Abstract
Low intestinal microbial diversity is associated with poor outcomes after allogeneic hematopoietic cell transplantation (HCT). Using 16S rRNA sequencing of 2067 stool samples and flow cytometry data from 2370 peripheral blood samples drawn from 894 patients who underwent allogeneic HCT, 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 posttransplant 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.