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.
Highlights
Chronic liver diseases and liver cirrhosis are on the rise in Europe [1]
The pathogenesis is still incompletely understood, currently, it is assumed that protein and urea breakdown by colonic bacteria leads to ammonia release, and due to the reduced capacity of the liver to detoxify, ammonia accumulates and is shunted into the systemic circulation [3,4]
Our retrospective analysis of 15 patients with oral LOLA intake for at least one month and propensity-score-matched controls showed that patients with LOLA intake show a higher abundance of the genera Flavonifractor and Oscillospira in the intestinal microbiome, a reduced ratio of ethanol to acetic acid in urine, an increased ratio of propylene glycol to isopropyl alcohol in stool, increased ratio of propylene glycol to valeric acid in stool, decreased ratio of valeric acid to glycerol in stool, increased levels of ornithine and decreased levels of leucine and isoleucine as well as lower levels of insulin-like growth factor (IGF)-1 in serum
Summary
Chronic liver diseases and liver cirrhosis are on the rise in Europe [1]. Hepatic encephalopathy (HE) is one of the most debilitating complications of cirrhosis and is associated with increased morbidity and mortality [2]. The pathogenesis is still incompletely understood, currently, it is assumed that protein and urea breakdown by colonic bacteria leads to ammonia release, and due to the reduced capacity of the liver to detoxify, ammonia accumulates and is shunted into the systemic circulation [3,4]. Ammonia accumulates in the brain and has neurotoxic effects, especially on astrocytes [5,6]. Available treatment modalities to lower ammonia include L-ornithine-L-aspartate (LOLA), nonabsorbable disaccharides (lactulose) and nonabsorbable antibiotics (rifaximin) [7].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
