Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as predictor of mortality in children

The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children likewise. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S rRNA amplicon sequencing to profile the gut microbiota and estimate diversity with the Shannon index. A global-to-local networking approach was used to characterize the ecological structure of the gut microbiota. Patients were stratified into higher- and lower-diversity groups at two timepoints: pre-transplantation and at neutrophil engraftment. The higher-diversity group prior to transplantation exhibited a higher probability of overall survival (88.9±5.7 standard error [SE] vs 62.7±8.2 [SE]) (p = 0.011) and lower incidence of grade II-IV (20.0±6.0 [SE] vs 44.4±7.4 [SE]) (p = 0.017) and grade III-IV acute graft-versus-host disease (aGvHD) (2.2±2.2 [SE] vs 20.0±6.0 [SE]) (p = 0.007). No significant difference in relapse-free survival was observed between the two groups (80.0±6.0 [SE] vs 55.4±10.8 [SE]) (p = 0.091). The higher-diversity group was characterized by higher relative abundances of potentially health-related families, such as Ruminococcaceae and Oscillospiraceae. In contrast, the lower-diversity group showed an overabundance of Enterococcaceae and Enterobacteriaceae. Network analysis detected short-chain fatty acid producers such as Blautia, Faecalibacterium, Roseburia, and Bacteroides as keystones in the higher-diversity group. Enterococcus, Escherichia-Shigella and Enterobacter were instead the keystones detected in the lower-diversity group. These results indicate that gut microbiota diversity and composition before transplantation correlate with survival and with the likelihood of developing aGvHD.