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. 2014 May;20(5):640-5.
doi: 10.1016/j.bbmt.2014.01.030. Epub 2014 Jan 31.

V体育官网 - 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

Ernst Holler  1 , Peter Butzhammer  2 , Karin Schmid  3 , Christian Hundsrucker  2 , Josef Koestler  4 , Katrin Peter  3 , Wentao Zhu  2 , Daniela Sporrer  3 , Thomas Hehlgans  5 , Marina Kreutz  3 , Barbara Holler  3 , Daniel Wolff  3 , Matthias Edinger  3 , Reinhard Andreesen  3 , John E Levine  6 , James L Ferrara  6 , Andre Gessner  4 , Rainer Spang  2 , Peter J Oefner  2
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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

Ernst Holler et al. Biol Blood Marrow Transplant. 2014 May.

Abstract

Next-generation sequencing of the hypervariable V3 region of the 16s rRNA gene isolated from serial stool specimens collected from 31 patients receiving allogeneic stem cell transplantation (SCT) was performed to elucidate variations in the composition of the intestinal microbiome in the course of allogeneic SCT. Metagenomic analysis was complemented by strain-specific enterococcal PCR and indirect assessment of bacterial load by liquid chromatography-tandem mass spectrometry of urinary indoxyl sulfate. At the time of admission, patients showed a predominance of commensal bacteria. After transplantation, a relative shift toward enterococci was observed, which was more pronounced under antibiotic prophylaxis and treatment of neutropenic infections. The shift was particularly prominent in patients that developed subsequently or suffered from active gastrointestinal (GI) graft-versus-host disease (GVHD). The mean proportion of enterococci in post-transplant stool specimens was 21% in patients who did not develop GI GVHD as compared with 46% in those that subsequently developed GI GVHD and 74% at the time of active GVHD. Enterococcal PCR confirmed predominance of Enterococcus faecium or both E. faecium and Enterococcus faecalis in these specimens. As a consequence of the loss of bacterial diversity, mean urinary indoxyl sulfate levels dropped from 42. 5 ± 11 μmol/L to 11. 8 ± 2. 8 μmol/L in all post-transplant samples and to 3. 5 ± 3 μmol/L in samples from patients with active GVHD VSports手机版. Our study reveals major microbiome shifts in the course of allogeneic SCT that occur in the period of antibiotic treatment but are more prominent in association with GI GVHD. Our data indicate early microbiome shifts and a loss of diversity of the intestinal microbiome that may affect intestinal inflammation in the setting of allogeneic SCT. .

Keywords: Clinical allogeneic transplantation; GVHD; Metagenomics; Microbiome. V体育安卓版.

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Conflict of interest statement

Conflict of interest statement: There are no conflicts of interest to report.

Figures (V体育平台登录)

Figure 1
Figure 1
Box plots of the 10 most variable bacteria in patients pretransplant and post-transplant with and without active GVHD. Data for each bacterium are grouped according to simultaneous use of antibiotics (no antibiotics or oral ciprofloxacin/oral trimethoprim/sulfamethoxazole and oral and systemic antibiotics). Boxes show the median and lower and upper quartiles, respectively, whereas the ends of the whiskers represent the minimum and maximum of all data after removal of outliers. The fraction of microbiome shown on the y-axis was iteratively renormalized as follows: For the most prominent bacterium, the absolute fraction is shown. All reads mapping to this bacterium where removed before calculating the relative fraction of the second most abundant bacterium. For calculating the fraction of the nth most abundant bacterium, all reads of the n-1 more frequent bacteria were removed.
Figure 2
Figure 2
Box plot of the risk of GI GVHD as a function of relative abundance of enterococci in stool specimens. Boxes show the median and lower and upper quartiles, respectively, whereas ends of the whiskers represent the 9th percentile and the 91st percentile. Outliers are shown as dots. Because the number of observations per patients varies substantially, we sampled 10,000 times randomly 2 observations per patient and averaged the number of enterococci. The distribution of risks across the 10,000 random samples is shown as box plots.
Figure 3
Figure 3
Time courses of urinary IS levels (µmol/L, ±2 standard errors). Significant drop of IS levels in relation to antibiotic prophylaxis (trimethoprim/sulfamethoxazole [Cotrim] until day −1, ciprofloxacin + metronidazole day −1 until engraftment [days 16 to 20]). Interaction of GVHD and antibiotic treatment is shown in Table 3.
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