4.7 Article

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

期刊

BLOOD
卷 139, 期 18, 页码 2758-2769

出版社

AMER SOC HEMATOLOGY
DOI: 10.1182/blood.2021014255

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资金

  1. National Institutes of Health (NIH), National Cancer Institute (NCI) Cancer Center Support Grant [P30-CA008748]
  2. NIH, NCI [P01-CA023766]
  3. American Society of Clinical Oncology (ASCO) young investigator award
  4. Hyundai Hope on Wheels young investigator award
  5. Cycle for Survival Equinox Innovation award
  6. Collaborative Pediatric Cancer Research Program Award
  7. Deutsche Forschungsgemeinschaft (DFG)
  8. American Society for Transplantation and Cellular Therapy (ASTCT)
  9. NIH, National Heart, Lung, and Blood Institute (NHLBI) [K08HL143189]
  10. Parker Institute for Cancer Immunotherapy at Memorial Sloan Kettering Cancer Center
  11. NCI [R01-CA228358, R01-CA228308]
  12. NHLBI [R01-HL125571, R01-HL123340]
  13. National Institute of Aging (NIA) [2 P01-AG052359]
  14. National institute of Allergy and Infectious Diseases (NIAID) [U01 AI124275]
  15. Lymphoma Foundation
  16. Susan and Peter Solomon Divisional Genomics Program
  17. DKMS (Deutsche KnochenMarkSpenderdatei or German Bone Marrow Donor File)
  18. Parker Institute for Cancer Immunotherapy
  19. Tri-Institutional Stem Cell Initiative award [2016-013]

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This study analyzed stool samples and peripheral blood samples from patients undergoing allogeneic hematopoietic cell transplantation, and found that the diversity of intestinal microbiota and the relative abundance of specific bacterial genera were associated with the recovery of immune cells.
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.

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