Oral Intake of L-Ornithine-L-Aspartate Is Associated with Distinct Microbiome and Metabolome Changes in Cirrhosis

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.

Ornithine aspartate effects on bacterial composition and metabolic pathways in a rat model of steatotic liver disease

“…So far, only a recent work analyzed microbiota changes at LOLA treatment. Horvath et al [ 21 ], 2022, evaluated the microbiota composition of 15 cirrhotic patients treated or not treated with LOLA. The authors reported no differences in alpha and beta diversities, but significant differential abundances in two genera ( i.e.…”

Intravenous versus oral ‘l-ornithine-l-aspartate’ in overt hepatic encephalopathy: a randomized comparative study

“…LOLA, when added to other anti-HE treatments, has been proven effective and should be used in therapy without hesitation. Moreover, beyond HE treatment, Horvath et al recently observed LOLA's positive impact on enhancing the microbiome and beneficial metabolomic changes, such as IGF-1 levels, in liver disease patients 27 .…”