Mortality and microbial diversity after allogeneic hematopoietic stem cell transplantation: secondary analysis of a randomized nutritional intervention trial

Kristin J Skaarud, Johannes R Hov, Simen H Hansen, Martin Kummen, Jørgen Valeur, Ingebjørg Seljeflot, Asta Bye, Vemund Paulsen, Knut E A Lundin, Marius Trøseid, Geir E Tjønnfjord, Per Ole Iversen, Kristin J Skaarud, Johannes R Hov, Simen H Hansen, Martin Kummen, Jørgen Valeur, Ingebjørg Seljeflot, Asta Bye, Vemund Paulsen, Knut E A Lundin, Marius Trøseid, Geir E Tjønnfjord, Per Ole Iversen

Abstract

Gut mucosal barrier injury is common following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and associated with poor clinical outcomes. Diet is critical for microbial diversity, but whether nutritional support affects microbiota and outcome after allo-HSCT is unknown. We present a secondary analysis of a randomized controlled nutritional intervention trial during allo-HSCT. We investigated if the intervention influenced gut microbiota, short-chain fatty acids (SCFAs), and markers of gut barrier functions, and if these parameters were associated with clinical outcomes. Fecal specimens were available from 47 recipients, and subjected to 16S rRNA gene sequencing. We found no significant differences between the intervention group and controls in investigated parameters. We observed a major depletion of microbiota, SCFAs, and altered markers of gut barrier function from baseline to 3 weeks post-transplant. One-year mortality was significantly higher in patients with lower diversity at 3 weeks post-HSCT, but not related to diversity at baseline. The relative abundance of Blautia genus at 3 weeks was higher in survivors. Fecal propionic acid was associated with survival. Markers of gut barrier functions were less strongly associated with clinical outcomes. Possibly, other strategies than dietary intervention are needed to prevent negative effects of gut microbiota and clinical outcomes after allo-HSCT.ClinicalTrials.gov (NCT01181076).

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Gut microbial diversity and the intervention and control group at baseline and 3 weeks. (a) Observed operational taxonomic units (OTUs) and groups, (b) Shannon diversity index and groups. Data are observed operational taxonomic units (OTUs) and Shannon diversity index given as individual values (dots) and box plots (median and interquartile range) with minimum and maximum values.
Figure 2
Figure 2
Fecal total SCFAs and the intervention and control group at baseline and 3 weeks. Data are total SCFAs given as individual values (dots) and box plots (median and interquartile range) with minimum and maximum values.
Figure 3
Figure 3
Markers of gut barrier functions and the intervention and control group at baseline and 3 weeks. (a) Intestinal fatty acid binding protein (I-FABP) and groups, (b) lipopolysaccharide binding protein (LBP) and groups. Data are I-FABP and LBP given as individual values (dots) and box plots (median and interquartile range) with minimum and maximum values.
Figure 4
Figure 4
Gut microbiota diversity and one-year survival. (a) Observed operational taxonomic units (OTUs) at baseline and 3 weeks and one-year survival, (b) Shannon diversity index at baseline and 3 weeks and one-year survival, (c) Loss of observed OTUs from baseline to 3 weeks and one-year survival. Data are observed OTUs and Shannon diversity index, and given as individual values (dots) and box plots (median and interquartile range) with minimum and maximum values.
Figure 5
Figure 5
Blautia abundance and one-year survival. (a) Blautia abundance at 3 weeks and one-year survival, (b) and (c) Drop in Blautia abundance from baseline to 3 weeks and one-year survival. Data are Blautia abundance given as individual values (dots) and box plots (median and interquartile range) with minimum and maximum values. Lines connect individual data points.

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