Altered urinary tryptophan metabolites in alcohol-associated liver disease

Raobo Xu; Vatsalya Vatsalya; Liqing He; Xipeng Ma; Wenke Feng; Craig J McClain; Xiang Zhang

doi:10.1111/acer.15148

Altered urinary tryptophan metabolites in alcohol-associated liver disease

Alcohol Clin Exp Res (Hoboken). 2023 Sep;47(9):1665-1676. doi: 10.1111/acer.15148. Epub 2023 Jul 17.

Authors

Raobo Xu^{1

2

3

4}, Vatsalya Vatsalya^{2

5}, Liqing He^{1

2

3

4}, Xipeng Ma^{1

2

3

4}, Wenke Feng^{2

3

5

6}, Craig J McClain^{2

3

5

6

7}, Xiang Zhang^{1

2

3

4

6}

Affiliations

¹ Department of Chemistry, University of Louisville, Louisville, Kentucky, USA.
² University of Louisville Alcohol Research Center, University of Louisville, Louisville, Kentucky, USA.
³ University of Louisville Hepatobiology and Toxicology Center of Biomedical Research Excellence, University of Louisville, Louisville, Kentucky, USA.
⁴ Center for Regulatory and Environmental Analytical Metabolomics, University of Louisville, Louisville, Kentucky, USA.
⁵ Department of Medicine, University of Louisville, Louisville, Kentucky, USA.
⁶ Department of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, USA.
⁷ Robley Rex Louisville VAMC, Louisville, Kentucky, USA.

PMID: 37431708
PMCID: PMC10782820 (available on 2024-09-01)
DOI: 10.1111/acer.15148

Abstract

Background: Alcohol-associated liver disease (ALD) leads to millions of deaths worldwide annually. A few potential biomarkers of ALD have been discovered through metabolomic or proteomic analysis. Tryptophan (Trp), one of nine essential amino acids, has been extensively studied and shown to play significant roles in many mammalian physiological processes. However, Trp metabolism changes in ALD are not yet fully understood. Whereas urine is an abundant and non-invasive source for disease biomarker discovery the current study investigated whether the abundance of Trp metabolites in the urine of ALD patients differs from that of healthy subjects. We also examined whether, if present in ALD, changes in urinary Trp metabolites can serve as markers for differentiating between mild/moderate and severe ALD.

Methods: We quantified the concentration of Trp and its metabolites in urine samples of healthy controls (n = 18), patients with mild or moderate alcohol-related liver injury (non-severe ALD; n = 21), and patients with severe alcohol-associated hepatitis (severe AH; n = 25) using both untargeted and targeted metabolomics.

Results: Eighteen Trp metabolites were identified and quantified from the untargeted metabolomics data. We developed a targeted metabolomics method to quantify the Trp and its metabolites and quantified 17 metabolites from the human urine samples. The data acquired in the untargeted and targeted platforms agreed and showed that the Trp concentration is not affected by the severity of ALD. However, the abundance of 10 Trp metabolites was correlated with the model for end-stage liver disease (MELD) score, with the abundance of nine metabolites significantly different between the healthy control and ALD patient groups.

Conclusion: We found that Trp metabolism differs between ALD patients and healthy controls even though the concentration of Trp was not affected. Two Trp metabolites, quinolinic acid and indoxyl sulfate, correlate highly with the severity of ALD.

Keywords: alcohol-associated liver disease; metabolomics; tryptophan metabolites; urine.

Abstract

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