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多组学视角下精神分裂症患者脂肪酸代谢的改变

Alterations in fatty acid metabolism in patients with schizophrenia in a multi-omics perspective.

作者信息

Chen Long, Wang Zhiqiang, Wang Yanyu, Jiang Haonan, Ding Yuntong, Xia Qingrong, Cheng Xialong, Zhang Xulai

机构信息

Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China.

Anhui Clinical Center for mental and psychological diseases, Hefei Fourth People's Hospital, 316 Mei shan Road, Hefei, Anhui 230000, China; Affiliated Psychological Hospital of Anhui Medical University, Hefei 230022, China,; Anhui Mental Health Center, Hefei 230000, China; School of Mental Health and Psychological Science, Anhui Medical University, Hefei 230022, China.

出版信息

Schizophr Res. 2025 May;279:94-105. doi: 10.1016/j.schres.2025.03.036. Epub 2025 Apr 3.

Abstract

BACKGROUND

Recent research has extensively explored the involvement of gut microbes in various fatty acid metabolic processes, elucidating their crucial roles in host energy homeostasis and metabolism. Nevertheless, there remains a dearth of studies examining the comprehensive profile of fatty acid metabolites in schizophrenia and their potential connection to gut microbes.

METHOD

Conducting a thorough investigation, this study scrutinized the gut microbiome composition of 63 individuals, consisting of 35 schizophrenia (SZ) patients and 28 demographically matched healthy control (HC) subjects. Feces and serum samples were meticulously collected, with stool samples subjected to 16S rRNA sequencing targeting region V4 and untargeted metabolomics analysis, while serum samples underwent untargeted metabolomics assessment.

RESULTS

A total of 21 different genus-level species were identified in the SZ and HC groups. Predictive analysis of gut flora pathways revealed abnormal fatty acid degradation in schizophrenia. Notably, 17 differential fatty acid metabolites were found in feces, whereas 43 were found in serum fatty acid metabolites. A higher proportion of differential fatty acid metabolites were found in serum compared to those in feces. The predominant pathways enriched in fatty acid metabolites included biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, and linoleic acid metabolism. Additionally, a significant correlation was noted between intestinal flora and fatty acids, as well as potential interactions between intestinal flora, fecal fatty acids and serum fatty acids.

CONCLUSIONS

Our multi-omics study provides new insights into the pathogenesis of schizophrenia, which may inform the treatment of neurodevelopmental disorders by modifying fatty acid metabolism through modulation of the gut microbiota.

摘要

背景

近期研究广泛探讨了肠道微生物在各种脂肪酸代谢过程中的参与情况,阐明了它们在宿主能量稳态和代谢中的关键作用。然而,关于精神分裂症中脂肪酸代谢物的全面概况及其与肠道微生物的潜在联系的研究仍然匮乏。

方法

本研究进行了全面调查,仔细研究了63名个体的肠道微生物群组成,其中包括35名精神分裂症(SZ)患者和28名人口统计学匹配的健康对照(HC)受试者。精心收集粪便和血清样本,粪便样本进行靶向V4区域的16S rRNA测序和非靶向代谢组学分析,而血清样本进行非靶向代谢组学评估。

结果

在SZ组和HC组中共鉴定出21种不同的属级物种。肠道菌群途径的预测分析显示精神分裂症中脂肪酸降解异常。值得注意的是,在粪便中发现了17种差异脂肪酸代谢物,而在血清脂肪酸代谢物中发现了43种。与粪便中的差异脂肪酸代谢物相比,血清中发现的差异脂肪酸代谢物比例更高。脂肪酸代谢物中富集的主要途径包括不饱和脂肪酸的生物合成、花生四烯酸代谢和亚油酸代谢。此外,还发现肠道菌群与脂肪酸之间存在显著相关性,以及肠道菌群、粪便脂肪酸和血清脂肪酸之间的潜在相互作用。

结论

我们的多组学研究为精神分裂症的发病机制提供了新的见解,这可能通过调节肠道微生物群来改变脂肪酸代谢,从而为神经发育障碍的治疗提供参考。

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