Original Article

Gut microbiota and graft-versus-host disease in hematopoietic stem cell transplant patients

Abstract

Background and Objectives: Graft-versus-host disease (GvHD) frequently complicates hematopoietic stem cell transplantation (HSCT). Emerging evidence suggests a correlation between gut microbiota and GvHD risk. This study aims to elucidate the microbiota profiles in HSCT patients before and after transplantation and their association with GvHD.
Materials and Methods: This study, conducted from December 2022 to December 2023, involved the collection of 15 stool samples from HSCT patients. Bacterial content was quantified using real-time PCR, while interleukin-6 levels were assessed via ELISA.
Results: Among the 15 participants (8 male, 7 female), 9 underwent allogeneic HSCT (allo-HSCT) and 6 received autologous HSCT. In the aGvHD group, there was a significant reduction in the abundance of Bacteroides and Bifidobacterium compared to those without aGvHD. Additionally, declines were observed in Clostridium and Firmicutes populations. The genus Blautia also showed reduced prevalence in the aGvHD group, whereas no significant differences were noted in the uncomplicated group. ELISA analysis revealed that interleukin-6 levels remained within the normal range (30-960 pg/ml) with no significant elevation in the aGvHD group.
Conclusion: The study highlights a notable association between alterations in gut microbiota, specifically reductions in certain bacterial populations and the development of aGvHD following allo-HSCT.

1. Gupta V, Braun TM, Chowdhury M, Tewari M, Choi SW. A systematic review of machine learning techniques in hematopoietic stem cell transplantation (HSCT). Sensors (Basel) 2020; 20: 6100.
2. Qian C, Wang Y, Reppel L, D'aveni M, Campidelli A, Decot V, et al. Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT. Bone Marrow Transplant 2018; 53: 114-122.
3. Fredricks DN. The gut microbiota and graft-versus-host disease. J Clin Invest 2019; 129: 1808-1817.
4. Ramachandran V, Kolli SS, Strowd LC. Review of graft-versus-host disease. Dermatol Clin 2019; 37: 569-582.
5. Malard F, Holler E, Sandmaier BM, Huang H, Mohty M. Acute graft-versus-host disease. Nat Rev Dis Primers 2023; 9: 27.
6. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet 2009; 373: 1550-1561.
7. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature 2007; 449: 804-810.
8. Sędzikowska A, Szablewski L. Human gut microbiota in health and selected cancers. Int J Mol Sci 2021; 22: 13440.
9. Andermann TM, Peled JU, Ho C, Reddy P, Riches M, Storb R, et al. The microbiome and hematopoietic cell transplantation: past, present, and future. Biol Blood Marrow Transplant 2018; 24: 1322-1340.
10. Holler E, Butzhammer P, Schmid K, Hundsrucker C, Koestler J, Peter K, et al. Metagenomic analysis of the stool microbiome in patients receiving allogeneic stem cell transplantation: loss of diversity is associated with use of systemic antibiotics and more pronounced in gastrointestinal graft-versus-host disease. Biol Blood Marrow Transplant 2014; 20: 640-645.
11. Peled JU, Devlin SM, Staffas A, Lumish M, Khanin R, Littmann ER, et al. Intestinal microbiota and relapse after hematopoietic-cell transplantation. J Clin Oncol 2017; 35: 1650-1659.
12. Ferrara JL. Pathogenesis of acute graft-versus-host disease: cytokines and cellular effectors. J Hematother Stem Cell Res 2000; 9: 299-306.
13. Zeiser R, Blazar BR. Pathophysiology of chronic graft-versus-host disease and therapeutic targets. N Engl J Med 2017; 377: 2565-2579.
14. Rychlik W. OLIGO 7 primer analysis software. Methods Mol Biol 2007; 402: 35-60.
15. Zhou J, Chen J, Peng Y, Xie Y, Xiao Y. A promising tool in serological diagnosis: current research progress of antigenic epitopes in infectious diseases. Pathogens 2022; 11: 1095.
16. Doki N, Suyama M, Sasajima S, Ota J, Igarashi A, Mimura I, et al. Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation. Ann Hematol 2017; 96: 1517-1523.
17. Li DS, Wu YR, Du WH, Zhu YL, Zhang WJ, Fu Y, et al. The composition of the intestinal microbiota after allogeneic haematopoietic stem cell transplantation and its association with graft versus host disease as assessed by 16Sribosomal ribonucleic acid. J Physiol Pharmacol 2023; 74: 10.26402/jpp.2023.1.10.
18. Kouidhi S, Souai N, Zidi O, Mosbah A, Lakhal A, Ben Othmane T, et al. High throughput analysis reveals changes in gut microbiota and specific fecal metabolomic signature in hematopoietic stem cell transplant patients. Microorganisms 2021; 9: 1845.
19. Jenq RR, Taur Y, Devlin SM, Ponce DM, Goldberg JD, Ahr KF, et al. Intestinal Blautia is associated with reduced death from graft-versus-host disease. Biol Blood Marrow Transplant 2015; 21: 1373-1383.
20. Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta) genomic data. mBio 2014; 5(2): e00889.
21. Metafuni E, Di Marino L, Giammarco S, Bellesi S, Limongiello MA, Sorà F, et al. The role of fecal microbiota transplantation in the allogeneic stem cell transplant setting. Microorganisms 2023; 11: 2182.
22. Narazaki M, Kishimoto T. The two-faced cytokine IL-6 in host defense and diseases. Int J Mol Sci 2018; 19: 3528.
23. Greco R, Lorentino F, Nitti R, Lupo Stanghellini MT, Giglio F, Clerici D, et al. Interleukin-6 as biomarker for acute GvHD and survival after allogeneic transplant with post-transplant cyclophosphamide. Front Immunol 2019; 10: 2319.
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IssueVol 16 No 5 (2024) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijm.v16i5.16800
Keywords
Gut microbiota; Hematopoietic stem cell transplantation; Graft-versus-host disease; Interleukin-6; Real-time polymerase chain reaction; Enzyme-linked immunosorbent assay

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How to Cite
1.
Panahi P, Hashemian AH, Payandeh M, Taghadosi M, Nomanpour B. Gut microbiota and graft-versus-host disease in hematopoietic stem cell transplant patients. Iran J Microbiol. 2024;16(5):648-654.