Circulating acylcarnitine alterations in glaucoma: an exploratory study on systemic metabolic association

Glaucoma is a leading cause of irreversible blindness and has increasingly been linked to systemic metabolic alterations. In particular, mitochondrial dysfunction affecting lipid metabolism may contribute to disease pathophysiology. Acylcarnitines, intermediates of mitochondrial fatty acid oxidation, represent markers of systemic metabolic status and may reflect alterations in energy metabolism relevant to glaucoma. The gut microbiome may modulate host metabolism through microbial metabolites and immune-related pathways. In this exploratory cross-sectional study, shotgun metagenomic sequencing and targeted metabolomics were integrated to investigate differences in gut microbial composition and circulating acylcarnitine profiles between 16 glaucoma patients and 16 healthy controls. Analysis of the gut microbiome revealed no differences in alpha diversity or overall community composition between groups. However, species-level analysis identified limited differences, including increased relative abundance of Candidatus Pararuminococcus gallinarum in glaucoma (exploratory false discovery rate threshold, q ≤ 0.25), which did not remain below this threshold when age was included as a fixed effect. In contrast, the overall circulating acylcarnitine profile was significantly associated with age (PERMANOVA, R² = 0.078, p = 0.033) but not independently with glaucoma status (R² = 0.052, p = 0.126) in this decomposition. At the individual metabolite level, circulating acylcarnitine profiles showed several exploratory FDR-selected associations with glaucoma status (q ≤ 0.25, strongest for hexadecenoylcarnitine, q = 0.105), with predominantly medium- and long-chain acylcarnitines showing higher levels in glaucoma patients, a pattern which may be consistent with altered mitochondrial lipid metabolism. Integrative analyses showed only limited associations between microbial taxa and circulating acylcarnitines. These findings suggest changes in systemic metabolism rather than in the gut microbiome. Larger studies are needed to further elucidate potential interactions between host metabolism and the gut microbiome in glaucoma. Trial registration: ClinicalTrials.gov, TRN NCT02438111, Registration date 28. April 2015.