DYSBIOSIS IN GUT MICROBIOTA AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION CAN BE DETERMINED BY THE COMBINATION OF CONDITIONING REGIMEN AND ANTIBIOTIC USAGE
Author(s): ,
Yasuyuki Arai
Affiliations:
Kyoto University,Kyoto,Japan
,
Takamitsu Tsukahara
Affiliations:
Institute of Nutrion & Pathology Inc.,Ujitawara,Japan
,
Miki Nagao
Affiliations:
Kyoto University,Kyoto,Japan
,
Tadakazu Kondo
Affiliations:
Kyoto University,Kyoto,Japan
Akifumi Takaori-Kondo
Affiliations:
Kyoto University,Kyoto,Japan
EHA Library. Arai Y. Jun 14, 2019; 266559; PF760
Dr. Yasuyuki Arai
Dr. Yasuyuki Arai
Contributions
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Abstract

Abstract: PF760

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background
Gut microbiota is known to change drastically after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and the change (“dysbiosis”) can be a predicting factor or the pathophysiological cause of post-transplant intestinal complications such as acute graft-versus-host disease (GVHD). The cause of dysbiosis, however, is not elucidated yet.

Aims
In this study, we analyzed gut microbiota consecutively after allo-HSCT along with the comprehensive analysis on metabolites, and determined the effects of conditioning regimens and post-transplant antibiotics.

Methods
We included 20 adult patients who underwent allo-HSCT in our institute (Kyoto University Hospital, Kyoto, Japan) after the written informed consent. Stool samples were collected at 7 timepoints in each patient (before conditioning, Day0, 7, 14, 21, 28, and 35), and bacterial population was determined using next generation sequence technique on 16S ribosomal RNA coding region. Sequence data along with metabolome using the same samples were compared with the clinical information.

Results
More than 100 samples were subjected the analysis. Shannon index which indicates diversity of microbiota demonstrated the highest values before transplant (4.075 in average), followed by the significant decrease after allo-HSCT (minimal, 2.469 on Day21, p < 0.05) and gradual recovery toward Day35 (2.736 in average). Chao1 index showed the same tendency; 93.478 before allo-HSCT, 43.456 on Day21, and 46.033 on Day35. Decrease of Shannon index and Chao1 index was more severely observed in patients treated with myeloablative conditioning (MAC) regimens than those with reduced-intensity conditioning (RIC).

Moreover, loss of microbiome diversity was also related to the residual antibiotic in stool samples; detection of piperacillin, which is derived from tazobactam/piperacillin, and meropenem showed strong correlation in a concentration-dependent manner. Fermentation in gut was not observed in these patients with metabolome analysis.

Conclusion
Types of conditioning regimens (MAC rather than RIC) and antibiotics were closely related to the dysbiosis after allo-HSCT and, as a result, abnormality in metabolome. They can be used as predictive factors for post-transplant gut dysfunction such as aGVHD.

Session topic: 22. Stem cell transplantation - Clinical

Keyword(s): Allogeneic hematopoietic stem cell transplant, Graft-versus-host disease (GVHD)

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