Lactobacillaceae-mediated eye-brain-gut axis regulates high myopia-related anxiety: from the perspective of predictive, preventive, and personalized medicine

Abstract

Background: High myopia has become a major cause of blindness worldwide and can contribute to emotional deficits through its impact on the central nervous system. The potential crosstalk with gut microbiome positions high myopia as a valuable model for studying the eye-brain-gut axis, highlighting the intricate interplay between visual health, neurological function, and the gut microbiome. Understanding these connections is crucial from a predictive, preventive, and personalized medicine (PPPM) perspective, as it may reveal novel intervention targets for managing both visual and mental health.

Working hypothesis and methodology: In our study, we hypothesized that visual stimuli associated with high myopia may lead to gut microecological dysregulation, potentially triggering mood disorders such as anxiety and depression. To test this hypothesis, we assessed genetic associations between high myopia (N = 50,372) and depression (N = 674,452) as well as anxiety (N = 21,761) using inverse variance weighted as the primary analytical method. We also investigated the potential mediating role of the gut microbiome (N = 18,340). The findings were validated in an independent cohort and summarized through meta-analysis.

Results: A genetic causal relationship between high myopia and anxiety was found (odds ratio [OR] = 8.76; 95% confidence interval [CI], 2.69-28.54; p = 3.16 × 10^-4), with 20.3% of the effect mediated by the gut microbiome family Lactobacillaceae (β = 0.517; 95% CI, 0.104-1.090; p = 0.037). The analysis also showed a suggestive causal relationship between high myopia and depression (OR = 1.25; 95% CI, 1.00-1.57; p = 0.048).

Conclusions: Our study shows that high myopia causes anxiety via the Lactobacillaceae family of the gut microbiome, supporting the eye-brain-gut axis concept. This underscores the need to shift from reactive to predictive, preventive, and personalized medicine (PPPM). Targeting Lactobacillaceae offers novel insights for early intervention and personalized treatment of high myopia-related anxiety and sheds light on interventions for other vision-related brain disorders.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-024-00387-z.

Keywords: Anxiety; Depression; Eye-brain-gut axis; Gut microbiome; High myopia; Lactobacillaceae; Neurological function; Predictive, preventive, and personalized medicine (PPPM / 3PM); Visual health.

Fig. 1

The study design of this two-sample MR analysis and two-step MR analysis. IVs, instrumental variables; MR, Mendelian randomization; SNPs, single nucleotide polymorphisms; GWAS, genome-wide association studies

Fig. 2

Circular heat map of MR analysis results. A From high myopia to gut microbiome. B From gut microbiome to anxiety (PGC). OR showed the estimated causal effect from the IVW method. Abbreviation: MR, Mendelian randomization; OR, odd ratio; IVW, inverse variance weighted; PWM, penalized weighted median; ML, maximum likelihood; RAPS, robust adjusted profile score

Fig. 3

The mediated effect of family Lactobacillaceae in the association between high myopia and anxiety. The effects (β and 95% CI) and p-value (from high myopia to anxiety, from high myopia to family Lactobacillaceae, and from family Lactobacillaceae to anxiety) were estimated by inverse variance weighted (IVW) of MR analysis. The estimated mediated effects (β and 95%CI) were calculated using the delta method, and the p-value was the result of the Sobel test. FDR, false discovery rate, represented the adjusted p-value