Intestinal Microbiota Can Predict Acute Graft-versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, whether intestinal microbiota can predict the development of aGVHD has been reported only rarely. Here we conducted a prospective study of microbiota in 141 patients after allogeneic hematopoietic stem cell transplantation. We found lower microbiota diversity in the aGVHD group compared with the non-aGVHD group at day 0 and day 15 ± 1 (P = .018 and .009, respectively). Diversity was negatively associated with conditioning intensity (P = .017, day 0; P = .045, day 15) and β-lactam antibiotic administration (P = .004, day 15). Intensified conditioning and β-lactam antibiotics were associated with a lower regulatory T (Treg)/T helper 17 (Th17) cell ratio at day 15 (P = .030 and .047, respectively). At day 15, the levels of the inflammatory factors (tumor necrosis factor α, interleukin [IL]-6, IL-17A, IL-1β, and lipopolysaccharide) were higher in the intensified conditioning group compared with the standard group (P < .05). The accumulated intestinal microbiota (AIM) score was defined as microbiota diversity and gradient of the 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) at day 15 post-transplantation. The AIM score was positively correlated with aGVHD grade (r = .481, P < .001), and the AIM score could be predictive of the development of aGVHD (grade II-IV aGVHD: area under the curve [AUC], .75, P < .001; grade III-IV aGVHD: AUC, .84, P < .001). These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development of aGVHD.

Keywords: Acute graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation; Intestinal microbiota; Microbiota diversity; Microbiota marker.