Clarifying the effect of gut microbiota on allergic conjunctivitis risk is instrumental for predictive, preventive, and personalized medicine: a Mendelian randomization analysis.

Background: Allergic conjunctivitis is an ocular immune disease which affects the conjunctiva, eyelids, and cornea. Growing evidence implicates the gut microbiota in balancing and modulating immunity response, and in the pathogenesis of allergic disease. As a result, gut microbial imbalance could be a useful indicator for allergic conjunctivitis. From the perspective of predictive, preventive, and personalized medicine (PPPM), clarifying the role of gut microbial imbalance in the development of allergic conjunctivitis could provide a window of opportunity for primary prediction, targeted prevention, and personalized treatment of the disease.

Working hypothesis and methodology: In our study, we hypothesized that individuals with microbial dysbiosis may be more susceptible to allergic conjunctivitis due to an increased inflammatory response. To verify the working hypothesis, our analysis selected genetic variants linked with gut microbiota features (N = 18,340) and allergic conjunctivitis (4513 cases, 649,376 controls) from genome-wide association studies. The inverse-variance weighted (IVW) estimate, Mendelian randomization (MR)-Egger, weighted median estimator, maximum likelihood estimator (MLE), and MR robust adjusted profile score (MR.RAPS) were employed to analyze the impact of gut microbiota on the risk of allergic conjunctivitis and identify allergic conjunctivitis-related gut microbes. Ultimately, these findings may enable the identification of individuals at risk of allergic conjunctivitis through screening of gut microbial imbalances, and allow for new targeted prevention and personalized treatment strategies.

Results: Genetic liability to Ruminococcaceae_UCG_002 (OR, 0.83; 95% CI, 0.70-0.99; P = 4.04×10^-2), Holdemanella (OR, 0.78; 95% CI, 0.64-0.96; P = 2.04×10^-2), Catenibacterium (OR, 0.69; 95% CI, 0.56-0.86; P = 1.09×10^-3), Senegalimassilia (OR, 0.71; 95% CI, 0.55-0.93; P = 1.23×10^-2) genus were associated with a low risk of allergic conjunctivitis with IVW. Besides, we found suggestive associations of a genetic-driven increase in the Oscillospira (OR, 1.41; 95% CI, 1.00-2.00; P = 4.63×10^-2) genus with a higher risk of allergic conjunctivitis. Moreover, MLE and MR.RAPS show consistent results with IVW after further validation and strengthened confidence in the true causal associations. No heterogeneity and pleiotropy was detected.

Conclusions: Our study suggests that gut microbiota may play a causal role in the development of allergic conjunctivitis and provides new insights into the microbiota-mediated mechanism of the disease. Gut microbiota may serve as a target for future predictive diagnostics, targeted prevention, and individualized therapy in allergic conjunctivitis, facilitating the transition from reactive medical services to PPPM in the management of the disease.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-023-00321-9.