The Gut Metabolism is altered in patients with CRB1-associated inherited retinal degeneration

Purpose: To compare the plasma metabolic profile of patients with a CRB1-associated inherited retinal degeneration (CRB1-IRD) with healthy controls (HCs). Design: A case-control study. Methods: Plasma concentration of 619 metabolites was measured with the MxP® Quant 500 Kit in 30 patients with a CRB1-IRD and 29 HCs. We fitted a linear regression model with adjustments for age and sex based on the concentration of metabolites in μM (μmol/L), or on the sums and ratios of metabolites, to determine differences between patients and controls. Results: Over-representation of pathways among metabolites associated strongest to CRB1-IRDs (P < 0.05, n = 62) identified amino acid pathways (such as beta-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.