Bile Acid Metabolism Changes in Patients with a CRB1-Associated Inherited Retinal Degeneration

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-01-07 DOI:10.1016/j.xops.2025.100704

Lude Moekotte MD, PhD , Joke H. de Boer MD, PhD , Sanne Hiddingh MSc , Bram Gerritsen PhD , Jutta Lintelmann PhD , Alexander Cecil PhD , L. Ingeborgh van den Born MD, PhD , Xuan-Thanh-An Nguyen MD, PhD , Camiel J.F. Boon MD, PhD , Maria M. van Genderen MD, PhD , Jonas J.W. Kuiper PhD

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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 Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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目的比较Crumbs同源物1相关遗传性视网膜变性（CRB1-IRD）患者与健康对照组（HCs）的血浆代谢谱。方法使用MxP Quant 500试剂盒测量代谢物浓度。我们根据代谢物的微摩尔（微摩尔/升）浓度或代谢物的总和和比值建立了一个线性回归模型，并对年龄和性别进行了调整，以确定患者和对照组之间的差异。结果由于肠道微生物群产生的脱氧胆酸衍生物减少，与CRB1-IRDs相关性最强的代谢物之间的通路代表性过高（P < 0.05，n = 62），确定了氨基酸通路（如β-丙氨酸、组氨酸和甘氨酸/丝氨酸）和胆汁酸生物合成。对整个血浆代谢轮廓进行的代谢类别富集分析进一步发现，脂质代谢物甘油磷脂、胆固醇酯和神经酰胺显著正富集，而胆汁酸代谢物则显著减少。结论脂质代谢改变和与微生物相关的次级胆汁酸浓度降低表明CRB1-IRD患者的肠道代谢发生了重大改变。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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