Metabolic Signature of Primary Biliary Cholangitis and Its Comparison with Celiac Disease

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by ongoing inflammatory destruction of the interlobular bile ducts, eventually leading to chronic cholestasis and biliary cirrhosis. This study primarily aims to define the metabolomic signature of PBC after comparison with healthy controls (HC). Secondly it aims at evaluating the possible metabolic association between PBC and coeliac disease (CD), an immune-mediated disorder frequently associated with PBC. Serum and urine samples from 20 PBC, 21 CD and 19 sex-matched HC subjects were collected. 1H NMR spectra for all samples were acquired, and multivariate statistics was used to evaluate the differences among the three groups and to provide information about the involved metabolites. The classification accuracies to discriminate PBC and HC groups were 78.9-84.6% for serum and 76.9% for urine. In comparison with HC, PBC patient sera were characterized by altered levels (P-value <0.05) of pyruvate, citrate, glutamate, glutamine, serine, tyrosine, phenylalanine and lactate. PBC patient urines showed lower levels (P-value <0.05) of trigonelline and hippurate with respect to HC. Furthermore, NMR metabolomic fingerprint showed to be able to cluster PBC with respect to CD patients, the classification accuracies in the discriminations between these groups were 81.9-91.7% for serum and 77.7% for urine. Our results show that PBC displays a unique metabolomic fingerprint, and lead to speculate about an impaired energy metabolism, probably associated with an altered gut microbiota. PBC and CD showed two distinct metabolic fingerprints. These data could provide clues for the comprehension of the PBC pathogenetic mechanisms and the detection of novel therapeutical targets.