Glaucoma Study Identifies Circulating Acylcarnitine Alterations Linked to Systemic Metabolism

In an exploratory cross-sectional study evaluating thirty-two individuals, researchers observed alterations in circulating acylcarnitines among glaucoma patients, pointing toward systemic metabolic shifts rather than substantial gut microbial disruptions.

Scientific interest has focused particularly on mitochondrial dysfunction affecting lipid metabolism as a potential contributor to disease pathophysiology. Because acylcarnitines serve as critical intermediates of mitochondrial fatty acid oxidation, they function as measurable indicators of systemic metabolic status and energy metabolism, while the gut microbiome has been hypothesized to modulate host metabolic processes through microbial metabolites and immune-related pathways.

To investigate potential biological differences, the research team designed an exploratory cross-sectional study that enrolled sixteen patients diagnosed with glaucoma and sixteen healthy control participants. The experimental protocol integrated two analytical modalities: targeted metabolomics to characterize circulating acylcarnitine species and shotgun metagenomic sequencing to profile gut microbial communities. This dual-omics strategy was implemented to examine whether systemic metabolic markers or gut microbiome configurations associate with glaucoma status.

Metagenomic profiling of the participants’ gut microbiomes demonstrated no significant differences between the glaucoma cohort and the healthy control cohort in overall microbial community composition.

At the species level, the investigators detected only limited differences across the gut microbial landscape. The relative abundance of Candidatus Pararuminococcus gallinarum was initially elevated in glaucoma patients under an exploratory false discovery rate threshold of q ≤ 0.25. However, this statistical association did not remain below the exploratory significance threshold after the researchers included age as a fixed effect in the analytical model.

Multivariate decomposition of the targeted metabolomic data showed that the overall circulating acylcarnitine profile was significantly associated with participant age, accounting for an R² of 0.078 with a p-value of 0.033 by PERMANOVA. In contrast, the overall profile was not independently associated with glaucoma status in this decomposition, yielding an R² of 0.052 with a p-value of 0.126.

Despite the lack of global profile divergence, individual metabolite analyses uncovered multiple exploratory associations with glaucoma status using a false discovery rate threshold of q ≤ 0.25. The strongest individual association was observed for hexadecenoylcarnitine, which demonstrated an exploratory q-value of 0.105.

Integrative analyses evaluating potential relationships between specific microbial taxa and circulating acylcarnitines revealed only limited cross-omic associations. The study authors concluded that the observed signatures primarily reflect alterations in systemic metabolism rather than gut microbial dysbiosis, noting that larger cohorts are required to clarify host-microbiome metabolic interactions in glaucoma. The study was registered under ClinicalTrials.gov identifier NCT02438111.

Subject of Research: Exploratory analysis of circulating acylcarnitine alterations and gut microbial composition in glaucoma

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

Article References: Haldimann, G., Spörri, L., Eldridge, N., Mathis, D., Largiadèr, C. R., Zinkernagel, M. S., Unterlauft, J. D., & Zysset-Burri, D. C. (2026). Circulating acylcarnitine alterations in glaucoma: an exploratory study on systemic metabolic association. BMC Microbiology. https://doi.org/10.1186/s12866-026-05917-5

Image Credits: AI Generated

DOI: 10.1186/s12866-026-05917-5

Keywords: Glaucoma, Acylcarnitines, Systemic metabolism, Mitochondrial dysfunction, Lipid metabolism, Fatty acid oxidation, Gut microbiome, Shotgun metagenomics, Targeted metabolomics, Hexadecenoylcarnitine, Candidatus Pararuminococcus gallinarum, Medium-chain acylcarnitines, Long-chain acylcarnitines, Host-microbiome interactions, Cross-sectional study, PERMANOVA, False discovery rate