S1623 intestinal microbiota can predict agvhd following allogeneic hematopoietic stem cell transplantation

Background: The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, it is not well known whether the intestinal microbiota at neutrophil engraftment could predict the occurrence and grades of aGVHD. Methods: We collected stool and blood samples from 141 patients undergoing allogeneic hematopoietic stem cell transplantation. The microbiota, the inflammatory factors and T lymphocyte subsets were detected at pre-conditioning, day 0 and day 15 post-transplantation. The abundance of bacterial that could predict aGVHD and diversity were included in accumulated intestinal microbiota (AIM) score.   Findings: We found microbiota diversity was associated with conditioning (P = 0.017, day 0 and P = 0.045, day 15) and β-lactam antibiotics (P = 0.004, day 15). Treg/Th17 ratio was positively correlated with microbial diversity (r = 0.216, P = 0.010), while it was negatively correlated with levels of TNF-α, IL-17A, IL-1β and LPS in plasma (r = -0.226, -0.225, -0.335, -0.291; P = 0.007, 0.010, < 0.001, < 0.001, respectively) at day 15. The accumulated intestinal microbiota (AIM) score at day 15 could be a predictor for the development of aGVHD (II-IV aGVHD: AUC = 0.75, P < 0.001; III-IV aGVHD: AUC = 0.84, P < 0.001). AIM score was also correlated with aGVHD grades (r = 0.481, P < 0.001).   Interpretations: These findings suggest intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and influence Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development and grades of aGVHD.   Funding: This work was funded by the National Natural Science Foundation of China (Nos. U1401221, 81770190, 81870144, 81600141, 81700176, and 81470349), the National primary research plan (Nos. 2017YFA105500 and 2017YFA105504). Science and Technology Major Planning Project of Guangdong Province (2014B020226004), Natural Science Foundation of Guangdong Province (No.2016A030310390), and Medical Science and Technology Planning Project of Henan Province (201403227). Declaration of Interest: The authors declare no competing financial interests. Ethical Approval: This study was approved by the ethical committee of the Nanfang Hospital, Southern Medical University, China. After approval of the study, the consent of the participants was signed for biospecimen collection and analysis. This study was conducted in accordance with the Declaration of Helsinki.