1H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression

Oh, Junsang; Kim, Jayoung; Lee, Sanghak; Park, Gyubin; Baritugo, Kei-Anne Garcia; Han, Ki Jun; Lee, Sangheun; Sung, Gi-Ho

doi:10.3390/metabo14010039

Open AccessArticle

¹H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression

by

Junsang Oh

^1,2,†,

Jayoung Kim

^1,3,†,

Sanghak Lee

⁴,

Gyubin Park

⁴,

Kei-Anne Garcia Baritugo

^1,2

,

Ki Jun Han

⁵,

Sangheun Lee

^1,5,* and

Gi-Ho Sung

^1,2,*

¹

Biomedical Institute of Mycological Resource, International St. Mary’s Hospital, College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea

²

Department of Convergence Science, College of Medicine, Catholic Kwandong University, Gangneung-si 25601, Gang-won-do, Republic of Korea

³

Department of Laboratory Medicine, International St. Mary’s Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea

⁴

Department of Biomedical Science, Graduate School, Catholic Kwandong University, Gangneung-si 25601, Gang-won-do, Republic of Korea

⁵

Department of Internal Medicine, International St. Mary’s Hospital, College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Metabolites 2024, 14(1), 39; https://doi.org/10.3390/metabo14010039

Submission received: 13 November 2023 / Revised: 28 December 2023 / Accepted: 3 January 2024 / Published: 8 January 2024

(This article belongs to the Topic Biomarker Development and Application)

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Abstract

Without early detection and treatment, chronic and excessive alcohol consumption can lead to the development of alcoholic liver disease (ALD). With this in mind, we exploit the recent concept of the liver–gut axis and analyze the serum profile of ALD patients for identification of microbiome-derived metabolites that can be used as diagnostic biomarkers for onset of ALD. ¹H-NMR was used to analyze serum metabolites of 38 ALD patients that were grouped according to their Child–Turcotte–Pugh scores (CTP): class A (CTP-A; 19), class B(CTP-B; 10), and class C (CTP-C; 9). A partial least squares-discriminant analysis (PLS-DA) and a variable importance of projection (VIP) score were used to identify significant metabolites. A receiver operating characteristic (ROC) curve and correlation heatmap were used to evaluate the predictability of identified metabolites as ALD biomarkers. Among 42 identified metabolites, 6 were significantly correlated to exacerbation of ALD. As ALD progressed in CTP-C, the levels of trimethylamine N-oxide (TMAO), malate, tyrosine, and 2-hydroxyisovalerate increased, while isobutyrate and isocitrate decreased. Out of six metabolites, elevated levels of TMAO and its precursors (carnitine, betaine, choline) were associated with severity of ALD. This indicates that TMAO can be used as an effective biomarker for the diagnosis of ALD progression.

Keywords: alcohol-related liver disease; trimethylamine N-oxide; serum metabolites; multivariate analysis; ¹H-NMR

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MDPI and ACS Style

Oh, J.; Kim, J.; Lee, S.; Park, G.; Baritugo, K.-A.G.; Han, K.J.; Lee, S.; Sung, G.-H. ¹H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression. Metabolites 2024, 14, 39. https://doi.org/10.3390/metabo14010039

AMA Style

Oh J, Kim J, Lee S, Park G, Baritugo K-AG, Han KJ, Lee S, Sung G-H. ¹H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression. Metabolites. 2024; 14(1):39. https://doi.org/10.3390/metabo14010039

Chicago/Turabian Style

Oh, Junsang, Jayoung Kim, Sanghak Lee, Gyubin Park, Kei-Anne Garcia Baritugo, Ki Jun Han, Sangheun Lee, and Gi-Ho Sung. 2024. "¹H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression" Metabolites 14, no. 1: 39. https://doi.org/10.3390/metabo14010039

APA Style

Oh, J., Kim, J., Lee, S., Park, G., Baritugo, K.-A. G., Han, K. J., Lee, S., & Sung, G.-H. (2024). ¹H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression. Metabolites, 14(1), 39. https://doi.org/10.3390/metabo14010039

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¹H NMR Serum Metabolomic Change of Trimethylamine N-oxide (TMAO) Is Associated with Alcoholic Liver Disease Progression

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