Abstract
PURPOSE: To compare the plasma metabolic profile of patients with a Crumbs homolog 1-associated inherited retinal degeneration (CRB1-IRD) with that of healthy controls (HCs). DESIGN: A case-control study. PARTICIPANTS: A cohort of 30 Dutch patients with CRB1-IRD and 29 Dutch HCs. METHODS: The MxP Quant 500 Kit was used for measuring metabolite concentrations. We fitted a linear regression model with adjustments for age and sex based on the concentration of metabolites in micromolar (micromoles per liter) or on the sums and ratios of metabolites to determine differences between patients and controls. MAIN OUTCOME MEASURES: Plasma concentration of 619 metabolites. RESULTS: Overrepresentation of pathways among metabolites associated strongest to CRB1-IRDs (P < 0.05, n = 62) identified amino acid pathways (such as β-alanine, histidine, and glycine/serine) and bile acid biosynthesis, driven by a decrease in deoxycholic acid derivatives produced by gut microbiota. Enrichment analysis of metabolic classes across the plasma metabolic profile further identified significant positive enrichment for lipid metabolites glycerophospholipids, cholesterol esters, and ceramides, and significant depletion for bile acid metabolites. Further investigation of the sums and ratios (i.e., metabolism indicators) ascertained a significant decrease in intestinal microbial-dependent secondary bile acid classes. CONCLUSIONS: Lipid metabolic alterations and decreased microbiota-related secondary bile acid concentrations indicate significant alterations in gut metabolism in patients with a CRB1-IRD. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.