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

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.

Biomarkers for Allogeneic HCT Outcomes

“…For instance, the presence of fecal butyrate and indole, in patients post-HCT directly correlated with enrichment of Clostridiales and Bacteriodales, respectively, in an analysis of 451 fecal specimen from 44 patients before HCT through 100 days post-HCT. Although fecal butyrate and indole did not impact aGVHD incidence or overall survival in these patients, low levels of butyrate were found in patients contracting blood stream infections within 30 days (90).…”

Effect of gut microbiota from Henoch-Schönlein Purpura patients on acid-sensitive ion channel 3 expression and intestinal motility in Germ-free rats

“…The colon has higher numbers of anaerobic bacteria and the dominant bacteria are Bacteroides, Bi dobacterium and fungi, while its pH ranges from 6.1 to 7.5. These intestinal orae are used to produce vitamins, fatty acids, bile acids and other products, while propionic acid, butyric acid, acetic acid and other short chain fatty acids (SCFAs) are usually the fermentation products of anaerobic bacteria [16,17]. The presence of a large number of SCFAs can reduce intestinal pH [18].…”

Targeting the gut microbiome in allogeneic hematopoietic stem cell transplantation

“…The materials summarized in Table 1 have been made available in the form of raw 16S data sets in the short read archive. Five of the six collected datasets 1/10 have been made available as part of scientific publication: PRJEB23820 [Biagi et al 2019], PRJEB16057 , PRJNA528754 [Galloway-Peña et al 2019], PRJNA592853 [D'Amico et al 2019] and PRJNA491657 [Taur et al 2018].…”

“…A lower GM diversity index at the time of engraftment (neutrophil recovery) has been associated in multiple studies with increased incidence of intestinal aGvHD disease and transplant related mortality (TRM) , Golob et al 2017, Han et al 2018, Galloway-Peña et al 2019. Enterococci have been proposed as a landmark for aGvHD whether induced by antibiotics or not [Holler et al 2014], whereas intestinal Blautia has been found associated with reduced death from aGvHD [Jenq et al 2015].…”