Related Experiment Video
Updated: Jan 18, 2026
Author Spotlight: Unraveling Vitamin A Transport Mechanisms — Linking Liver Receptors to Vision Health Through RBPR2 and RBP4 Interactions
Published on: October 4, 2024
Bile Acid Metabolism Changes in Patients with a CRB1-Associated Inherited Retinal Degeneration
Lude Moekotte1, Joke H de Boer1, Sanne Hiddingh1
1Department of Ophthalmology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
Patients with Crumbs homolog 1-associated inherited retinal degeneration (CRB1-IRD) show altered gut metabolism, including lipid changes and reduced secondary bile acids. These findings highlight significant metabolic differences compared to healthy individuals.
Area of Science:
- Ophthalmology
- Metabolomics
- Genetics
Background:
- Inherited retinal degenerations (IRDs) are a group of genetic disorders affecting vision.
- Crumbs homolog 1 (CRB1)-associated IRD is a severe form of inherited retinal disease.
- Understanding the systemic metabolic consequences of CRB1-IRD is crucial for comprehensive patient care.
Purpose of the Study:
- To compare the plasma metabolic profiles of patients with CRB1-IRD and healthy controls (HCs).
- To identify specific metabolic pathways and metabolite classes altered in CRB1-IRD.
Main Methods:
- A case-control study involving 30 Dutch patients with CRB1-IRD and 29 Dutch HCs.
- Plasma concentrations of 619 metabolites were measured using the MxP Quant 500 Kit.
- Linear regression models were used to determine differences between patients and controls, adjusting for age and sex.
Main Results:
- Significant overrepresentation of amino acid pathways (e.g., $\beta$-alanine, histidine, glycine/serine) and bile acid biosynthesis pathways were identified in CRB1-IRD patients.
- A decrease in deoxycholic acid derivatives, produced by gut microbiota, was observed.
- Enrichment analysis revealed significant increases in lipid metabolites (glycerophospholipids, cholesterol esters, ceramides) and depletion of bile acid metabolites.
- A significant decrease in intestinal microbial-dependent secondary bile acid classes was confirmed.
Conclusions:
- Patients with CRB1-IRD exhibit significant alterations in lipid metabolism.
- Decreased concentrations of microbiota-related secondary bile acids suggest impaired gut metabolism in CRB1-IRD.
- These findings indicate substantial gut metabolic changes associated with CRB1-IRD.
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.
