Potential Protective Role of Bifidobacteria in Myopia Prevention: Evidence from Full-Length 16S rRNA Sequencing and Bidirectional Mendelian Randomization Analysis

Guodong Tang¹Yibo Han²Xiaoqi Gong²Xuejing Wang¹Jing Li²Jun Zhang²Junru Wang²Jike Song^2,3,4Hongsheng Bi^1,3,4*

• ¹Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Jinan, China
• ²Shandong University of Traditional Chinese Medicine, Jinan, China
• ³Shandong Academy of Eye Disease Prevention and Therapy, Jinan, China
• ⁴Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, China

The increasing prevalence of myopia worldwide poses significant public health concerns. Accumulating evidence suggests a potential link between ocular diseases and the gut microbiota (GM); however, whether the GM directly contributes to myopia development remains to be established. This study investigated the potential causal link between the GM and myopia through bidirectional Mendelian randomization (MR) analysis, further validated by experiments conducted on a form-deprivation myopia (FDM) guinea pig model. Bidirectional two-sample MR analysis was performed using genome-wide association study summary statistics comprising data on 196 GM taxa from the MiBioGen consortium and myopia-associated data from the FinnGen database. Instrumental variables were carefully selected according to predetermined standards. Subsequently, MR estimates were calculated using the inverse variance weighted, MR-Egger regression, and weighted median approaches, along with supplementary sensitivity evaluations. Concurrently, FDM was experimentally induced in guinea pigs, and fecal samples were subjected to comprehensive fulllength 16S rRNA gene sequencing analysis. MR analysis identified five bacterial taxa linked to the risk of myopia. Specifically, higher Bifidobacterium abundance was associated with lower myopia risk (odds ratio = 0.834, 95% confidence interval = 0.705-0.986, p < 0.05). Animal experiments validated the MR findings, demonstrating a significant enrichment of Bifidobacteria in control animals. Conclusively, supplementation with Bifidobacteria is a potential strategy for reducing the risk of myopia. Future research should focus on developing and testing Bifidobacterium-based interventions to validate their effectiveness in controlling myopia.