Targeted metabolomics reveals aberrant profiles of serum bile acids in patients with schizophrenia

Abstract

Emerging evidence indicates that bile acids (BAs), which are signaling molecules that regulate metabolism and inflammation, appear to be dysregulated in schizophrenia (SZ). Further investigation is warranted to comprehensively characterize BA profiles in SZ. To address this, we analyzed serum BA profiles in 108 drug-free patients with SZ and in 108 healthy controls (HCs), divided into a discovery set (n = 119) and a validation set (n = 97), using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Forty serum BAs were detected and absolutely quantified using calibration curves. Global BA profiling showed differences in SZ and HC groups in both discovery and validation sets. The concentrations of chenodeoxycholic acid, ursodeoxycholic acid, 3β-chenodeoxycholic acid, 7-ketolithocholic acid, 3-dehydrocholic acid, total BAs, and unconjugated BAs were significantly lower in patients with SZ compared with HCs in the two sample sets. The BA deconjugation potentials by gut microbiota and the affinity index of the farnesoid X receptor (FXR) were notably decreased in SZ patients compared to those of HCs. Conjugated BAs and BA deconjugation potentials differed in SZ patients with first versus recurrent episodes, although similar BA profiles were observed in both groups. In addition, a panel of 8 BA variables acted as a potential auxiliary diagnostic biomarker in discriminating SZ patients from HCs, with area under the curve values for receiver operating characteristic curves of 0.758 and 0.732 and for precision-recall curves of 0.750 and 0.714 in the discovery and validation sets, respectively. This study has provided compelling evidence of comprehensive characteristics of circulating BA metabolism in patients with SZ and promoted a deeper understanding of the role of BAs in the pathophysiology of this disease, possibly via the gut microbiota-FXR signaling pathway.