Association between ocular surface microbiota species and type 2 diabetes mellitus with or without retinopathy and...

Diabetic retinopathy (DR) is the most prevalent blinding microvascular complication of diabetes mellitus. Although altered ocular surface microbiota (OSM) has been recently linked to type 2 diabetes mellitus (DM) and diabetic retinopathy (DR), its involvement in these diseases remains to be elucidated at the species level. Our current study investigated 92 conjunctival sac swabs from 28 nondiabetic controls (NC) and 64 type 2 DM patients, including 31 with DR and 33 without DR (non-DR, NDR), for species-resolved OSM profiles using 2bRAD-M sequencing, and investigated their correlations with clinical parameters. A total of 232 species were identified in the study, with 12.5% and 10.8% exclusively observed in DR and NDR, respectively. Significant differences in beta diversity, but not in alpha diversity, were observed in DR compared to NDR and NC. Substantial changes in OSM species composition were observed in DM compared to NC, most attributable to DR. Commensal bacterial species, especially Actinomycetota species, such as Bifidobacterium infantis, and fungal species, such as Malassezia restricta, substantially decreased in DM. In contrast, species mainly belonging to the Pseudomonadota phylum, such as Pseudomonas and Pseudomonas aeruginosa, increased in DM, especially in DR. Moreover, such differential OSM species exhibited a significant correlation with clinical parameters, especially those associated with blood sugar indices, kidney complications, or insulin treatment, with Acinetobacter johnsonii being the most positively correlated with glycosylated hemoglobin A1c. Our current study revealed substantially altered OSM species profiles associated with DM/DR, suggesting a potential role for OSM species and providing new insights into the clinical correlation and diagnostic value of OSM.

Our research characterizes the ocular surface microbiota (OSM) at the species level in patients with type 2 diabetes mellitus (DM), both with and without diabetic retinopathy (DR and NDR), using 2bRAD-M sequencing. It uncovers unique microbial signatures, notably the reduction of commensal Actinomycetota and Malassezia restricta, and the increase of opportunistic Pseudomonadota such as Pseudomonas aeruginosa and Acinetobacter johnsonii. These microbial changes are linked to glycemic control, kidney function, and systemic inflammation, connecting local ocular microbiota to systemic microvascular damage. The study also highlights OSM species with strong diagnostic potential for DM and DR, indicating that noninvasive, microbiota-based biomarkers could supplement existing imaging-based screening. Overall, these findings deepen the understanding of host-microbiota interactions in diabetes and retinopathy and support future research into mechanisms, longitudinal effects, and microbiota-targeted therapies to prevent or reduce vision-threatening diabetic complications.