The correlation in the microbiome analysis of the conjunctiva and the gut between ocular graft-versus-host disease patients and graft-versus-host disease model mice.

Abstract

Purpose : Graft- versus- host disease (GVHD) is the most frequent and lethal complication after allogeneic hematopoietic stem cell transplantation (HSCT). The ocular region such as the conjunctiva and the lacrimal glands can be affected by GVHD. It is well-documented that the microbiome is related to the immune system and that symptoms of chronic GVHD are similar to those of autoimmune diseases. We reported that the alteration of the microbiome could result in the mitigation of ocular GVHD in mice (ARVO 2018, 2019). With our promising data, we investigated whether our findings could be extended from mice to humans.

Methods : The 16S rRNA microbiome analysis was conducted to delve into HSCT recipients’ conjunctiva and gut as well as their murine counterparts. The GVHD mouse model was produced as previously described (Zhang, Y. et al J Immunol. 2002). The human conjunctival samples were collected according to the protocol (#20090277) approved by the institutional ethics review board of the Keio University School of Medicine. We divided the human subjects into 3 groups; 1) GVHD group which showed the phenotypes of GVHD, 2) non-GVHD group which received HSCT and did not show any GVHD findings, and 3) healthy control. The same division was applied to the murine subjects. It should be noted that we utilized the criteria of ocular GVHD that were defined by the international chronic ocular GVHD consensus group(Ogawa Y. et al. Sci Rep. 2013).

Results : In the microbiome analysis, Bifidobacterium was lower in the gut from the mice affected by GVHD than that from the control mice. In contrast, Pseudomonas was higher in the gut from the mice with GVHD compared to that in their control counterparts. Moreover, Bifidobacterium was low in the GVHD patients' conjunctiva compared to the healthy controls. Furthermore, Pseudomonas was higher in the GVHD patients' conjunctiva compared to the healthy controls. Interestingly, a similar trend was observed in untreated mice with GVHD and antibiotics-administrated ones in which ocular and systemic GVHD was profoundly reduced.

Conclusions : We found a similar tendency in the 16S rRNA microbiome analysis between GVHD patients and a mouse model of GVHD. The results suggest that a similar microbiome is involved in the development of ocular GVHD in humans and mice.

This is a 2020 ARVO Annual Meeting abstract.