Multi-omics Mendelian Randomization Reveals Immunometabolic Signatures of the Gut Microbiota in Optic Neuritis and the Potential Therapeutic Role of Vitamin B6

Abstract

Optic neuritis (ON) is an inflammatory condition often linked to autoimmune disorders like multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Despite its low incidence, ON can lead to severe, irreversible visual impairment. Emerging evidence suggests the gut microbiota (GM) may influence ON through complex immune and metabolic pathways, yet the mechanisms remain underexplored. This study employed a multi-omics Mendelian randomization (MR) approach to assess the causal relationships between GM taxa and ON. We analyzed data from extensive genetic and metabolic profiling, examining the causal effect between 473 GM taxa, 731 immune cells/traits, 1400 metabolites, vitamin B6, and ON. Our methodology involved two-sample MR analysis to establish causality and mediation analysis to explore the mechanisms between GM and ON and potential therapeutic strategies. We identified 27 GM taxa with a direct causal relationship to ON risk. Further analysis highlighted three GM taxa with particularly strong associations. Mediation analysis revealed specific metabolic and immune pathways through which these taxa exert their effects, including notable interactions with vitamin B6 metabolism, which appeared to mediate some of these relationships. We found that vitamin B6 could be a potential therapeutic method by acting on GM in ON. This study advances our understanding of the complex etiology of ON and highlights the potential of GM as a target for therapeutic strategies. The significant role of vitamin B6 suggests new avenues for prevention and treatment, emphasizing the need for further research into diet-based interventions.

Keywords: Gut microbiota; Immune cells; Mendelian randomization; Optic neuritis; Vitamin B6.

Fig. 1

The study design and overview

Fig. 2

The MR result of GM and ON. A The result shows the causal effect between three GM taxa and ON. B–D The scatter plot of MR result of three GM taxa and ON

Fig. 3

The volcano plot of the MR result. A The volcano plot shows the most significant immune cells that have a causal relationship with ON. B The volcano plot shows the most significant metabolites that have a causal relationship with ON

Fig. 4

The enrichment analysis. A The metabolite enrichment of ON in different enrichment ratios. B The top 25 metabolic pathways associated with ON, with red being the most significant

Fig. 5

The mediation analysis of vitamin B6 and ON mediated by GM