Shared household environment structures the gut microbiota in a large family cohort with central areolar choroidal dystrophy

Abstract

Central areolar choroidal dystrophy (CACD) is a rare monogenic hereditary retinal dystrophy characterised by progressive retinal pigment epithelium and choriocapillaris atrophy, photoreceptor loss, oxidative stress, and chronic inflammation. Emerging evidence suggests that the gut microbiota can modulate systemic inflammatory responses and may influence ocular health through the gut-eye axis. However, the contribution of the gut microbiota to CACD remains unexplored. In this pilot study, we investigated the gut microbiota composition of members of a large Spanish family carrying the PRPH2 Arg195Leu mutation associated with CACD. Faecal samples from 33 mutation carriers and 24 non-carrier household members were analysed using whole-metagenome shotgun sequencing. Taxonomic composition and bacterial diversity were compared adjusting for sequencing depth, age, and sex, accounting for shared household environment through paired and mixed-effects analyses. The findings suggest that gut microbiota variation in this CACD cohort is primarily driven by shared environmental factors rather than disease status at this depth of sequencing. Our study highlights the critical importance of accounting for household effects in microbiome studies of familial and rare genetic diseases and provides a robust framework for future investigations into the gut-eye axis using longitudinal or interventional designs.