Gut microbiota dynamic signature and antibiotic-induced dysbiosis in hematopoietic stem cell transplantation patients as well as potential microbiome biomarker discovery for prognosis

Little is known about the early diagnosis and biomarkers for graft versus host diseases (GVHD) and nonrelapse mortality in hematopoietic stem cell transplantation (HSCT) recipients. This study therefore was conducted to reveal dynamic changes in gut microbiota (GM) during different stage of HSCT, and to analyze impact of specific antibiotics on GM, aimed to identify diagnostic markers to predict acute GVHD (aGVHD) and outcomes based on GM. Accordingly, 41 hematological patients undergoing HSCT were recruited. 149 fecal samples were collected at seven indicated time points, and GM composition was determined by 16SrRNA sequencing. Distinct dynamics in GM diversity were observed across precondition and post-transplant phases. Moreover, GM diversity significantly declined in patients who ever used Biapenem (P=0.018) or Cefmerazole sodium (P=0.025) compared to those never used. During neutrophil engraftment, the GM abundence was also significantly different between aGVHD 1-2 and 3-4 groups, namely, Clostridiales, Lachnospiraceae and Ruminococcaceae were predominant in aGVHD 1-2, while Weissella viridescens was enriched in aGVHD 3-4. And in non-relapsing death group, Enterococcus was richer. Overall, Biapenem and Cefmerazole sodium had independent effects on the GM after HSCT. Furthermore, Clostridiales, Lachnospiraceae, Ruminococcaceae, Weissella viridescens, and Enterococcus were specific biomarkers correlated to aGVHD and consistent with clinical severity.