Altered fecal and plasma metabolic signatures and increased inflammatory markers in patients with acute anterior uveitis

Abstract

Purpose : Acute anterior uveitis (AAU) is the most common uveitis, and is often accompanied by other inflammatory diseases such as ankylosing spondylitis. While AAU has been associated with gut microbial dysbiosis, its functional impact on disease pathogenesis remains unclear. Our study aimed to assess whether AAU patients exhibit distinct fecal and plasma metabolic profiles compared to healthy controls (HC).

Methods : Patients diagnosed with acute anterior uveitis (AAU) and healthy controls (HC) provided consent following an IRB-approved protocol and their stool and blood samples were collected. Fecal and plasma metabolites from AAU and HC were isolated and profiled with liquid chromatography-mass spectrometry (LC-MS) for untargeted metabolomic analysis. Fecal and plasma marker of inflammation (calprotectin), and plasma levels of bacterial endotoxin (LPS) were also measured in AAU and HC.

Results : The fecal metabolomic analysis included 52 subjects (26 AAU and 26 HC), whereas the plasma metabolomic analysis included 69 subjects (31 AAU and 38 HC). Both fecal and plasma cohorts had age, sex, and BMI matched samples in AAU and HC groups. Of these cohorts, paired fecal and plasma samples were obtained from 22 AAU patients and 26 HC. Metabolomic profiling revealed distinct fecal and plasma metabolic signatures in AAU patients. Of interest, fecal levels of various inflammatory metabolites (e.g. palmitoyl carnitine, stearoyl-L-carnitine, biliverdin) were significantly (p<0.05) increased, while anti-inflammatory metabolites such as naringenin were significantly decreased in AAU patients in comparison with HC. Furthermore, the plasma of AAU patients exhibited significantly elevated levels of inflammatory metabolites such as phenylacetylglutamine and 3- indoxy sulphate, 5-oxi-proline, adenosine, etc. In addition, AAU patients had a significant increase in the levels of fecal and plasma calprotectin and plasma LPS levels in comparison with HC.

Conclusions : Our study demonstrates that AAU patients exhibit increased carnitine, bile acid, and inflammatory metabolites with a concomitant decrease in anti-inflammatory metabolites in fecal and plasma samples. Future investigations aimed at understanding the mechanisms underlying these metabolic perturbations may identify novel metabolites as therapeutic strategies for AAU and other inflammatory diseases.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.