Abstract

Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation (allo-HSCT). We evaluated if the oral mucosa microbiota (OM) could impact the outcomes in patients who underwent allo-HSCT. Samples from the oral mucosa of 30 patients were collected at three time points: before the conditioning regimen, at aplasia, and at engraftment. We analyzed the associations of OM diversity and composition with allo-HSCT outcomes. Lower OM diversity at preconditioning was associated with a higher risk of relapse at 3 years (68% versus 33%, respectively; P = 0.04). Dominance (relative abundance ≥ 30%) by a single genus at preconditioning was also associated with a higher risk of relapse (63% versus 36% at 3 years, respectively; P = 0.04), as well as worse progression-free survival (PFS; 19% versus 55%, respectively; P = 0.01), and overall survival (OS) at 3 years (38% versus 81%, respectively; P = 0.02). In our study we observed that OM dysbiosis is associated with a higher risk of relapse and worse survival after allo-HSCT.

Highlights

  • Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation

  • To the best of our knowledge, this is the first study to evaluate the possible impact of the oral mucosa microbiota (OM) using amplicon sequencing variants (ASVs) on allo-HSCT outcomes

  • ASVs, which are read sequences denoised to single-nucleotide resolution, is a more reproducible and comprehensive technique with higher sensitivity and specificity than operational taxonomic units (OTU) in analyzing ­microbiota[44,45,46]

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Summary

Introduction

Intestinal microbiota (IM) diversity and composition regulates host immunity and affects outcomes after allogeneic stem cell transplantation (allo-HSCT). We evaluated if the oral mucosa microbiota (OM) could impact the outcomes in patients who underwent allo-HSCT. We analyzed the associations of OM diversity and composition with allo-HSCT outcomes. In our study we observed that OM dysbiosis is associated with a higher risk of relapse and worse survival after allo-HSCT. Abbreviations 95% Cis Ninety-five percent confidence intervals aGVHD Acute GVHD allo-HSCT Allogeneic stem cell transplantation ASVs Amplicon sequencing variants cGVHD Chronic GVHD DRI Disease risk index GVHD Graft versus host disease IM Intestinal microbiota NRM Non-relapse mortality OM Oral mucosa microbiota OS Overall survival PFS Progression-free survival. IM disruption, characterized by significant changes in microbiota diversity and composition, is associated with allo-HSCT clinical outcomes. In allo-HSCT, IM disruption is associated with the incidence of G­ VHD20–22, overall survival (OS)[23,24,25,26], and underlying disease r­ elapse[27,28]

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