Association of lipopolysaccharide, a gut bacterial toxin, with retinal neurodegeneration

Abstract

Purpose : Lipopolysaccharide (LPS) is a potent pro-inflammatory toxin originating from gut bacteria and there is emerging evidence of a link between gut microbiota and neuroinflammation leading to retinal neurodegeneration. The retinal nerve fiber layer (RNFL) thinning is a hallmark of glaucoma, the second leading cause of blindness worldwide, and a biomarker of retinal neurodegeneration. We assessed the association of a blood biomarker of LPS exposure with RNFL thickness at baseline and with longitudinal RNFL thickness changes.

Methods : The Alienor study is a prospective population-based study, based on 963 residents of Bordeaux (France), aged 73 years or more at baseline. Esterified 3-hydroxy fatty acids (3-OH FAs) were measured as a proxy of total plasma LPS burden, using Liquid Chromatography Tandem Mass Spectrometry. RNFL thickness was measured using optical coherence tomography imaging every two years from 2009 to 2017 (5 follow-up visits). Associations of plasma esterified 3-OH FAs with RNFL thickness were assessed using linear mixed models adjusted for potential confounders and imputation for missing covariates.

Results : In the studied sample of 703 participants, mean age at baseline was 82.3 ± 4.2 and 61.9 % of the participants were women. Exposure to higher plasma esterified 3-OH FAs was significantly associated with thinner RNFL at baseline (Standardized Coefficient Beta (ß)= -1.42, 95% confidence interval (CI) [-2.56; - 0.28], p = 0.01). This association remained stable after multivariate adjustment for potential confounders (ß= -1.21, CI [-2.24; - 0.18], p = 0.02). No statistically significant association was found of 3-OH FAs with longitudinal RNFL thickness changes.

Conclusions : This study evidenced a positive association between higher plasma esterified 3-OH FAs and retinal neurodegeneration. These results suggest that exposure to LPS may be involved in the early pathophysiological processes of glaucoma and highlight the potential importance of the human gut microbiota in preserving retinal health.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.