A gut microbiota score predicting acute graft-versus-host disease following myeloablative allogeneic hematopoietic stem cell transplantation

Abstract

Although studies have reported that intestinal microbiota are associated with acute graft‐versus‐host disease (aGVHD), they lacked a satisfactory method for predicting aGVHD. We collected stool and blood samples at day 15 posttransplant from 150 patients from two centers who underwent myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Stool microbiota were detected by 16S ribosomal RNA gene sequencing; inflammatory factors and T lymphocytes were detected by multiplex immunoassays and flow cytometry, respectively. A gut microbiota score (GMS) from a LASSO (least absolute shrinkage and selection operator) model was developed and validated to predict aGVHD. In the discovery cohort, the GMS could predict II‐IV aGVHD (area under the receiver operating characteristic [ROC] curve [AUC] = 0.904, P < .0001). Furthermore, the validation model was consistent with the discovery set (AUC = 0.887, P < .0001). Regulatory T/T‐helper 17 (Treg/Th17) cells ratio in the low GMS subgroup was higher compared with the high GMS (P = .012), and the validation set is consistent with the discovery set (P = .003). In addition, high cytokine levels were associated with high GMS. In conclusion, the GMS at neutrophil engraftment could predict aGVHD, and it was a potential and novel method. The GMS was associated with the inflammatory factor and Treg/Th17 balance.

The impact of intestinal microbiota in antithymocyte globulin–based myeloablative allogeneic hematopoietic cell transplantation

“…32 To improve the prognostic values for clinical outcomes, studies also tried to establish microbiota-compositional score systems. 5,33 Nevertheless, it is currently unrealistic to predict clinical outcome through precise characterization of an individual intestinal microbiota.…”

Applications of gut microbiota in patients with hematopoietic stem-cell transplantation

“…Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality [9]. The microbiota can be used as predictor of mortality in allo-HSCT [10], and the constitution of the intestinal microbiota at neutrophil engraftment and GM score can predict the development of aGvHD following myeloablative allo-HSCT [24,25]. These results supported the idea for modulation of the GM in patients with HSCT.…”

Opportunities and Challenges for Gut Microbiota in Acute Leukemia

“…A study by Han L et al. found more gut microbiota diversity in the non-aGVHD group than in the aGVHD group ( 91 ), they evaluated the gut microbiota to predict GVHD and found that Lachnospiraceae and Peptostreptococcaceae were negatively associated with GVHD, while Enterobacteriaceae were positively associated with aGVHD ( 91 ). Lachnospiraceae was negatively correlated with severe aGVHD, and levels of all major SFCAs were significantly decreased in patients with severe aGVHD, with a 75.8% decrease in acetate, a 95.8% decrease in propionate, and a 94.6% decrease in butyrate, while propionate levels were retained in patients with mild aGVHD.…”