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Open Forum Infect Dis. 2019 Apr 4;6(5):ofz173. doi: 10.1093/ofid/ofz173. eCollection 2019 May.

Fecal Microbiome, Metabolites, and Stem Cell Transplant Outcomes: A Single-Center Pilot Study.

Author information

1
Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas MD Anderson Cancer Center, Houston.
2
Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston.
3
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston.
4
Department of Epidemiology and Biostatistics, Long School of Medicine and Mays Cancer Center, University of Texas Health Science Center at San Antonio.
5
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston.
6
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston.
7
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston.

Abstract

Background:

Accumulating evidence suggests that the intestinal microbiome may dramatically affect the outcomes of hematopoietic stem cell transplant (HSCT) recipients. Providing 16S ribosomal RNA based microbiome characterization in a clinically actionable time frame is currently problematic. Thus, determination of microbial metabolites as surrogates for microbiome composition could offer practical biomarkers.

Methods:

Longitudinal fecal specimens (n = 451) were collected from 44 patients before HSCT through 100 days after transplantation, as well as 1-time samples from healthy volunteers (n = 18) as controls. Microbiota composition was determined using 16S ribosomal RNA V4 sequencing. Fecal indole and butyrate levels were determined using liquid chromatography tandem mass spectrometry.

Results:

Among HSCT recipients, both fecal indole and butyrate levels correlated with the Shannon diversity index at baseline (P = .02 and P = .002, respectively) and directly after transplantation (P = .006 and P < .001, respectively). Samples with high butyrate levels were enriched for Clostridiales, whereas samples containing high indole were also enriched for Bacteroidales. A lower Shannon diversity index at the time of engraftment was associated with increased incidence of acute intestinal graft-vs-host disease (iGVHD) (P = .02) and transplant-related deaths (P = .03). Although fecal metabolites were not associated with acute iGVHD or overall survival, patients contracting bloodstream infections within 30 days after transplantation had significantly lower levels of fecal butyrate (P = .03).

Conclusions:

Longitudinal analysis of fecal microbiome and metabolites after HSCT identified butyrate and indole as potential surrogate markers for microbial diversity and specific taxa. Further studies are needed to ascertain whether fecal metabolites can be used as biomarkers of acute iGVHD or bacteremia after HSCT.

KEYWORDS:

butyrate; graft-vs-host disease (GVHD); hematopoietic stem cell transplant (HSCT); indole; microbiome

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