Deciphering the Transformed bacterial ocular surface microbiome in diabetic mice and its Consequential influence on corneal wound healing restoration

Abstract

To obtain a profound understanding of microbiome variations and their associations with diabetic cornea wound healing, a type 1 diabetic mouse model and a corneal epithelial wound healing model were established. Corneal tissues from diabetic mice and healthy controls were collected. The 2bRAD sequencing for microbiome (2bRAD-M)technique was used to analyze the ocular microbiome profiles. Fifty-five distinct bacterial species were identified through alignment against the 2bRAD-M database. Among all the species identified on the corneal wound, 17 (30.91 %) unique species were discovered on the diabetic epithelium side, 13 (23.64 %) on the non-diabetic epithelium side, and 25 (45.45 %) species were common to both. The top five most abundant bacterial species on the non-diabetic side were Exiguobacterium sibiricum (26.50 %), Enterobacter hormaechei (13.37 %), Brevibacillus agri (6.24 %), Ralstonia sp. UNC404CL21Col (6.11 %), and Cupriavidus pauculus (5.71 %). On the diabetic side, the predominant five species were Methylobacterium sp. MB200 (38.73 %), Exiguobacterium sibiricum (11.58 %), Acinetobacter johnsonii (9.80 %), Corynebacterium glutamicum (6.46 %), and Corynebacterium stationis (5.71 %). Increased levels of gram-negative bacilli, such as Methylobacterium, in the diabetic ocular surface microbiota may be involved in the delayed healing of corneal wounds. Gatifloxacin eye drops with antibacterial activity against gram-negative bacteria were applied to the ocular surface. The corneal epithelium of diabetic mice healed more rapidly after the application of gatifloxacin eye drops. The changes in the ocular surface microbiota of diabetic corneal wounds may be related to delayed healing of the corneal epithelium in diabetic mice, providing a new research target for the investigation of this pathology.