TY - JOUR
T1 - Fecal microbiome, metabolites, and stem cell transplant outcomes
T2 - A single-center pilot study
AU - Galloway-Pena, Jessica
AU - Peterson, Christine B.
AU - Malik, Farida
AU - Sahasrabhojane, Pranoti V.
AU - Shah, Dimpy Jagdish
AU - Brumlow, Chelcy E.
AU - Carlin, Lily G.
AU - Chemaly, Roy F.
AU - Im, Jin Seon
AU - Rondon, Gabriela
AU - Felix, Edd
AU - Veillon, Lucas
AU - Lorenzi, Philip L.
AU - Alousi, Amin M.
AU - Jenq, Robert R.
AU - Kontoyiannis, Dimitrios P.
AU - Shpall, Elizabeth J.
AU - Shelburne, Samuel A.
AU - Okhuysen, Pablo C.
N1 - Funding Information:
Financial support. This work was supported by the MD Anderson Cancer Center (MDACC) (S. A. S. and P. C. O.; Multidisciplinary Research Program funding to D. P. K. and E. J. S.; and Odyssey Fellowship Program support to J. R. G. P.); the CFP Foundation (J. R. G. P.); and the American Cancer Society (Mentored Research Scholar Grants in Applied and Clinical Research, MRSG-16-152-01-CCE to D.P.S.) The Grant–Biostatistics Shared Resource (C.B.P.) and the Proteomics and Metabolomics Core Facility (L. V. and P. L. L.) are supported by the National Cancer Institute, National Institutes of Health Cancer Center Support Grant (grant 4P30CA016672-41. The Proteomics and Metabolomics Core Facility (L. V. and P. L. L.) is also supported by the Cancer Prevention and Research Institute of Texas (grant RP130397), and the National Institutes of Health (grant 1S10OD012304-01).
Publisher Copyright:
© The Author(s) 2019.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
KW - Butyrate
KW - Graft-vs-host disease (GVHD)
KW - Hematopoietic stem cell transplant (HSCT)
KW - Indole
KW - Microbiome
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U2 - 10.1093/ofid/ofz173
DO - 10.1093/ofid/ofz173
M3 - Article
C2 - 31065565
AN - SCOPUS:85067203435
SN - 2328-8957
VL - 6
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
IS - 5
ER -