Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease Journal Article
| Authors: | Burgos da Silva, M.; Ponce, D. M.; Dai, A.; Devlin, S. M.; Gomes, A. L. C.; Moore, G.; Slingerland, J.; Shouval, R.; Armijo, G. K.; DeWolf, S.; Fei, T.; Clurman, A.; Fontana, E.; Amoretti, L. A.; Wright, R. J.; Andrlova, H.; Miltiadous, O.; Perales, M. A.; Taur, Y.; Peled, J. U.; van den Brink, M. R. M. |
| Article Title: | Preservation of the fecal microbiome is associated with reduced severity of graft-versus-host disease |
| Abstract: | Following allogeneic hematopoietic cell transplantation (allo-HCT), the gastrointestinal (GI) tract is frequently affected by acute graft-versus-host disease (aGVHD), the pathophysiology of which is associated with a dysbiotic microbiome. Since microbial composition varies along the length of the GI tract, the authors hypothesized that microbiome features correlate with the pattern of organ involvement after allo-HCT. We evaluated 266 allo-HCT recipients from whom 1303 stool samples were profiled by 16S ribosomal gene sequencing. Patients were classified according to which organs were affected by aGVHD. In the 20 days prior to disease onset, GVHD patients had lower abundances of members of the class Clostridia, lower counts of butyrate producers, and lower ratios of strict-to-facultative (S/F) anaerobic bacteria compared with allograft recipients who were free of GVHD. GI GVHD patients showed significant reduction in microbial diversity preonset. Patients with lower GI aGVHD had lower S/F anaerobe ratios compared with those with isolated upper GI aGVHD. In the 20 days after disease onset, dysbiosis was observed only in GVHD patients with GI involvement, particularly those with lower-tract disease. Importantly, Clostridial and butyrate-producer abundance as well as S/F anaerobe ratio were predictors of longer overall survival; higher abundance of butyrate producers and higher S/F anaerobe ratio were associated with decreased risk of GVHD-related death. These findings suggest that the intestinal microbiome can serve as a biomarker for outcomes of allo-HCT patients with GVHD. © 2022 The American Society of Hematology |
| Keywords: | adult; controlled study; aged; major clinical study; overall survival; busulfan; fludarabine; nonhuman; methotrexate; prospective study; biological marker; bortezomib; multiple myeloma; cyclophosphamide; melphalan; hematopoietic stem cell transplantation; chronic myeloid leukemia; thiotepa; acute graft versus host disease; disease severity; hla matching; myeloablative conditioning; myelodysplastic syndrome; nonmyeloablative conditioning; whole body radiation; graft versus host reaction; reduced intensity conditioning; allogeneic hematopoietic stem cell transplantation; umbilical cord blood; graft survival; enterococcus; intestine flora; microbiology; calcineurin inhibitor; tacrolimus; graft vs host disease; rna 16s; chronic lymphatic leukemia; peripheral blood stem cell transplantation; onset age; feces; sirolimus; cyclosporine; graft recipient; clofarabine; bacterium; butyric acid; adverse event; prolymphocytic leukemia; bacteria; microflora; klebsiella; microbiota; target organ; microbial diversity; actinobacteria; bacteroidetes; eubacterium; lactobacillus; proteobacteria; streptococcus; escherichia; staphylococcus; butyric acid derivative; butyrates; mycophenolate mofetil; feces microflora; clostridiales; metagenomics; maraviroc; humans; human; male; female; article; rna sequencing; anaerobic bacterium; population abundance; dysbiosis; blautia; lachnospiraceae; ruminococcaceae; mismatched unrelated donor; matched related donor; matched unrelated donor; parabacteroides; ruminococcus; clostridia; akkermansia; anaerobe; coprococcus |
| Journal Title: | Blood |
| Volume: | 140 |
| Issue: | 22 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2022-12-01 |
| Start Page: | 2385 |
| End Page: | 2397 |
| Language: | English |
| DOI: | 10.1182/blood.2021015352 |
| PUBMED: | 35969834 |
| PROVIDER: | scopus |
| PMCID: | PMC9837450 |
| DOI/URL: | |
| Notes: | Erratum issued, see DOI: [10.1182/blood.2023019750] -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work