The ocular surface microbiome in patients following hematopoietic stem cell transplantation

Abstract

Purpose: Hematopoietic stem cell transplantation (HSCT), or bone marrow transplantation, is a medical procedure used to treat diseases related to faulty blood-producing and immune systems. A significant chronic complication that may arise in HSCT recipients is graft-versus-host disease (GVHD). Noteworthy alterations have been observed in the gut microbiome of HSCT recipients, correlating with complications such as GVHD. However, few studies have focused on changes in the ocular surface microbiome post-HSCT and the corresponding clinical outcomes. Therefore, this study aimed to investigate the ocular surface microbiome in HSCT patients and its potential impact on ocular GVHD. Methods: A prospective investigation of the ocular surface microbiome in HSCT patients was conducted. Conjunctival swabs were collected from 17 HSCT recipients at three time points: before the transplant, 6 months post-transplant, and 12 months post-transplant. The microbial profile was assessed using 16S rRNA gene sequencing and analyzed with the QIIME2 microbiome analysis pipeline. Microbiome comparisons between pre- and post-HSCT were performed, including alpha diversity analyses (e.g., Chao1 index, Shannon Diversity Index) and beta diversity analyses (e.g., Bray-Curtis dissimilarity, Faith’s Phylogenetic Diversity). Additionally, bacterial differential abundance and diversity among different severity levels of ocular GVHD in post-HSCT patients were compared using statistical methods such as Linear Discriminant Analysis Effect Size (LEfSe) and Permutational Multivariate Analysis of Variance (PERMANOVA). Results: A significant increase in local ocular surface microbiome diversity, including observed features and the Chao1 index, was observed following HSCT. The genus TM7x was identified as a potential biomarker, showing a strong association with the onset of ocular GVHD. These findings suggest that alterations in the ocular microbiome may indicate the development of ocular GVHD in HSCT recipients. Conclusion: This study presents the first comprehensive longitudinal analysis of the ocular surface microbiome in HSCT patients in Hong Kong. The critical role of microbiome changes in the ocular health of HSCT recipients was underscored. The identification of TM7x as a potential biomarker for ocular GVHD highlights the importance of microbiome monitoring in improving the management and therapeutic strategies for ocular GVHD in HSCT patients.