Qing Ying, Wang Pengkun, Cui Gaoping, Zhang Juan, Liang Kemei, Xia Zhong, Wang Peng, He Lin, Jia Wei
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200030, China.
The Fourth People's Hospital of Wuhu, Wuhu, 241003, China.
Schizophrenia (Heidelb). 2022 Aug 18;8(1):65. doi: 10.1038/s41537-022-00273-5.
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.
新出现的证据表明，胆汁酸（BAs）作为调节代谢和炎症的信号分子，在精神分裂症（SZ）中似乎失调。有必要进一步研究以全面表征SZ患者的胆汁酸谱。为了解决这个问题，我们使用超高效液相色谱三重四极杆质谱法分析了108例未服用药物的SZ患者和108例健康对照者（HCs）的血清胆汁酸谱，分为发现集（n = 119）和验证集（n = 97）。检测到40种血清胆汁酸，并使用校准曲线进行绝对定量。整体胆汁酸谱分析显示，在发现集和验证集中，SZ组和HC组存在差异。在两个样本组中，SZ患者的鹅去氧胆酸、熊去氧胆酸、3β-鹅去氧胆酸、7-酮石胆酸、3-脱氢胆酸、总胆汁酸和未结合胆汁酸的浓度均显著低于HCs。与HCs相比，SZ患者肠道微生物群的胆汁酸去结合潜力和法尼醇X受体（FXR）的亲和力指数显著降低。首发与复发的SZ患者的结合胆汁酸和胆汁酸去结合潜力不同，尽管两组的胆汁酸谱相似。此外，一组8个胆汁酸变量在区分SZ患者和HCs方面可作为潜在的辅助诊断生物标志物，在发现集和验证集中，受试者操作特征曲线的曲线下面积值分别为0.758和0.732，精确召回曲线的曲线下面积值分别为0.750和0.714。这项研究提供了令人信服的证据，证明了SZ患者循环胆汁酸代谢的综合特征，并促进了对胆汁酸在该疾病病理生理学中作用的更深入理解，可能是通过肠道微生物群-FXR信号通路实现的。
