Oral Intake of L-Ornithine-L-Aspartate Is Associated with Distinct Microbiome and Metabolome Changes in Cirrhosis |
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Authors: | Angela Horvath Julia Traub Benard Aliwa Benjamin Bourgeois Tobias Madl Vanessa Stadlbauer |
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Affiliation: | 1.Department of Gastroenterology and Hepatology, Medical University of Graz, 8036 Graz, Austria; (A.H.); (B.A.);2.Center of Biomarker Research in Medicine, CBmed GmbH Graz, 8010 Graz, Austria;3.Department of Clinical Medical Nutrition, University Hospital Graz, 8036 Graz, Austria;4.Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging Molecular Biology and Biochemistry, Medical University of Graz, 8036 Graz, Austria; (B.B.); (T.M.);5.BioTechMed-Graz, 8010 Graz, Austria |
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Abstract: | L-ornithine L-aspartate (LOLA) is administered as a therapeutic and/or preventive strategy against hepatic encephalopathy either intravenously or orally in patients with liver cirrhosis. Here, we analyzed how LOLA influences the microbiome and metabolome of patients with liver cirrhosis. We retrospectively analyzed the stool microbiome, stool, urine and serum metabolome as well as markers for gut permeability, inflammation and muscle metabolism of 15 cirrhosis patients treated orally with LOLA for at least one month and 15 propensity-score-matched cirrhosis patients without LOLA. Results were validated by comparing the LOLA-treated patients to a second set of controls. Patients with and without LOLA were comparable in age, sex, etiology and severity of cirrhosis as well as PPI and laxative use. In the microbiome, Flavonifractor and Oscillospira were more abundant in patients treated with LOLA compared to the control group, while alpha and beta diversity were comparable between groups. Differences in stool and serum metabolomes reflected the pathophysiology of hepatic encephalopathy and confirmed LOLA intake. In the urine metabolome, ethanol to acetic acid ratio was lower in patients treated with LOLA compared to controls. LOLA-treated patients also showed lower serum levels of insulin-like growth factor (IGF) 1 than patients without LOLA. No differences in gut permeability or inflammation markers were found. A higher abundance of Flavonifractor and Oscillospira in LOLA-treated patients could indicate LOLA as a potential microbiome modulating strategy in patients with liver disease. The lower levels of IGF1 in patients treated with LOLA suggest a possible link between the pathophysiology of hepatic encephalopathy and muscle health. |
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Keywords: | microbiome metabolome L-ornithine-L-aspartate cirrhosis hepatic encephalopathy |
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