The Detection of Primary Sclerosing Cholangitis Using Volatile Metabolites in Fecal Headspace and Exhaled Breath

Overview

Journal Metabolites

Publisher MDPI

Date 2024 Jan 22

PMID 38248826

Authors

Robert van Vorstenbosch

Kim van Munster

Danielle Pachen

Alex Mommers

Georgios Stavropoulos

Frederik-Jan van Schooten

Cyriel Ponsioen

Agnieszka Smolinska

Affiliations

Soon will be listed here.

Abstract

Up to 5% of inflammatory bowel disease patients may at some point develop primary sclerosing cholangitis (PSC). PSC is a rare liver disease that ultimately results in liver damage, cirrhosis and liver failure. It typically remains subclinical until irreversible damage has been inflicted. Hence, it is crucial to screen IBD patients for PSC, but its early detection is challenging, and the disease's etiology is not well understood. This current study aimed at the early detection of PSC in an IBD population using Volatile Organic Compounds in fecal headspace and exhaled breath. To this aim, fecal material and exhaled breath were collected from 73 patients ( = 16 PSC/IBD; = 8 PSC; = 49 IBD), and their volatile profile were analyzed using Gas Chromatography-Mass Spectrometry. Using the most discriminatory features, PSC detection resulted in areas under the ROC curve (AUCs) of 0.83 and 0.84 based on fecal headspace and exhaled breath, respectively. Upon data fusion, the predictive performance increased to AUC 0.92. The observed features in the fecal headspace relate to detrimental microbial dysbiosis and exogenous exposure. Future research should aim for the early detection of PSC in a prospective study design.

Citing Articles

Progress and challenges of developing volatile metabolites from exhaled breath as a biomarker platform.

Chou H, Godbeer L, Allsworth M, Boyle B, Ball M Metabolomics. 2024; 20(4):72.

PMID: 38977623 PMC: 11230972. DOI: 10.1007/s11306-024-02142-x.

References

Lemoinne S, Kemgang A, Belkacem K, Straube M, Jegou S, Corpechot C . Fungi participate in the dysbiosis of gut microbiota in patients with primary sclerosing cholangitis. Gut. 2019; 69(1):92-102. DOI: 10.1136/gutjnl-2018-317791. View

Longo V, Forleo A, Ferramosca A, Notari T, Pappalardo S, Siciliano P . Blood, urine and semen Volatile Organic Compound (VOC) pattern analysis for assessing health environmental impact in highly polluted areas in Italy. Environ Pollut. 2021; 286:117410. DOI: 10.1016/j.envpol.2021.117410. View

Trottier J, Bialek A, Caron P, Straka R, Heathcote J, Milkiewicz P . Metabolomic profiling of 17 bile acids in serum from patients with primary biliary cirrhosis and primary sclerosing cholangitis: a pilot study. Dig Liver Dis. 2011; 44(4):303-10. DOI: 10.1016/j.dld.2011.10.025. View

Chen X, Zhang Z, Li H, Zhao J, Wei X, Lin W . Endogenous ethanol produced by intestinal bacteria induces mitochondrial dysfunction in non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2020; 35(11):2009-2019. DOI: 10.1111/jgh.15027. View

Huang Y, Zhang S, Weng J, Huang D, Gu W . Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis. Open Med (Wars). 2022; 17(1):915-929. PMC: 9106112. DOI: 10.1515/med-2022-0481. View

Kurada S, Alkhouri N, Fiocchi C, Dweik R, Rieder F . Review article: breath analysis in inflammatory bowel diseases. Aliment Pharmacol Ther. 2014; 41(4):329-41. DOI: 10.1111/apt.13050. View

Dieterle F, Ross A, Schlotterbeck G, Senn H . Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Anal Chem. 2006; 78(13):4281-90. DOI: 10.1021/ac051632c. View

Kummen M, Thingholm L, Ruhlemann M, Holm K, Hansen S, Moitinho-Silva L . Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis. Gastroenterology. 2021; 160(5):1784-1798.e0. PMC: 7611822. DOI: 10.1053/j.gastro.2020.12.058. View

Garner C, Smith S, de Lacy Costello B, White P, Spencer R, Probert C . Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease. FASEB J. 2007; 21(8):1675-88. DOI: 10.1096/fj.06-6927com. View

10.

Karlsen T, Folseraas T, Thorburn D, Vesterhus M . Primary sclerosing cholangitis - a comprehensive review. J Hepatol. 2017; 67(6):1298-1323. DOI: 10.1016/j.jhep.2017.07.022. View

11.

van Vorstenbosch R, van Munster K, Stavropoulos G, Pachen D, van Schooten F, Ponsioen C . The potential of volatile organic compounds to diagnose primary sclerosing cholangitis. JHEP Rep. 2024; 6(8):101103. PMC: 11315128. DOI: 10.1016/j.jhepr.2024.101103. View

12.

Couch R, Dailey A, Zaidi F, Navarro K, Forsyth C, Mutlu E . Alcohol induced alterations to the human fecal VOC metabolome. PLoS One. 2015; 10(3):e0119362. PMC: 4353727. DOI: 10.1371/journal.pone.0119362. View

13.

Engel J, Blanchet L, Bloemen B, van den Heuvel L, Engelke U, Wevers R . Regularized MANOVA (rMANOVA) in untargeted metabolomics. Anal Chim Acta. 2015; 899:1-12. DOI: 10.1016/j.aca.2015.06.042. View

14.

van Vorstenbosch R, Cheng H, Jonkers D, Penders J, Schoon E, Masclee A . Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia. Metabolites. 2023; 13(1). PMC: 9865897. DOI: 10.3390/metabo13010055. View

15.

Little R, Wine E, Kamath B, Griffiths A, Ricciuto A . Gut microbiome in primary sclerosing cholangitis: A review. World J Gastroenterol. 2020; 26(21):2768-2780. PMC: 7284173. DOI: 10.3748/wjg.v26.i21.2768. View

16.

Guazzotti V, Hendrich V, Gruner A, Fiedler D, Stormer A, Welle F . Migration of Styrene in Yogurt and Dairy Products Packaged in Polystyrene: Results from Market Samples. Foods. 2022; 11(14). PMC: 9323499. DOI: 10.3390/foods11142120. View

17.

Smolinska A, Hauschild A, Fijten R, Dallinga J, Baumbach J, Schooten F . Current breathomics--a review on data pre-processing techniques and machine learning in metabolomics breath analysis. J Breath Res. 2014; 8(2):027105. DOI: 10.1088/1752-7155/8/2/027105. View

18.

Smolinska A, Tedjo D, Blanchet L, Bodelier A, Pierik M, Masclee A . Volatile metabolites in breath strongly correlate with gut microbiome in CD patients. Anal Chim Acta. 2018; 1025:1-11. DOI: 10.1016/j.aca.2018.03.046. View

19.

Stavropoulos G, van Munster K, Ferrandino G, Sauca M, Ponsioen C, van Schooten F . Liver Impairment-The Potential Application of Volatile Organic Compounds in Hepatology. Metabolites. 2021; 11(9). PMC: 8471934. DOI: 10.3390/metabo11090618. View

20.

. EASL Clinical Practice Guidelines: management of cholestatic liver diseases. J Hepatol. 2009; 51(2):237-67. DOI: 10.1016/j.jhep.2009.04.009. View