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双相情感障碍患者队列中,非典型抗精神病药物与肠道微生物群的相互作用

Interaction Between Atypical Antipsychotics and the Gut Microbiome in a Bipolar Disease Cohort.

作者信息

Flowers Stephanie A, Evans Simon J, Ward Kristen M, McInnis Melvin G, Ellingrod Vicki L

机构信息

College of Pharmacy, University of Michigan, Ann Arbor, Michigan.

Department of Psychiatry, University of Michigan, Ann Arbor, Michigan.

出版信息

Pharmacotherapy. 2017 Mar;37(3):261-267. doi: 10.1002/phar.1890. Epub 2017 Feb 20.

Abstract

OBJECTIVES

The atypical antipsychotic (AAP) class is often associated with metabolic disease, but the mechanistic underpinnings of this risk are not understood. Due to reports linking gut bacteria function to metabolic disease, we hypothesize that AAP treatment in adults results in gut dysbiosis potentiating metabolic criteria. This report describes recent findings linking AAP treatment with differences in gut microbiota communities in a human cohort with bipolar disorder (BD).

METHODS

In a cross-sectional design, we obtained 16S ribosomal sequences from 117 BD patients (49 AAP treated, 68 non-AAP treated). Analysis of molecular variance (AMOVA) was used to detect significant clustering of microbial communities between groups, and the inverse Simpson Diversity Index was used to calculate alpha diversity. Detection of differentially abundant operational taxonomic units (OTUs) between groups was performed using linear discriminant analysis effect size.

RESULTS

The AAP-treated cohort was significantly younger and had an increased body mass index compared with non-AAP-treated patients. Groups did not differ in other psychotropic medication use with the exception of higher use of benzodiazepines in the AAP cohort. We detected significant separation between microbiota communities of AAP-treated and nontreated patients (AMOVA; p=0.04). AAP-treated females showed significant decreased species diversity when compared with non-AAP-treated females (p=0.015). Males showed no significant diversity between treatment groups (p=0.8). Differentially abundant OTUs between treatment groups were OTU1, OTU25, and OTU32 that classified to Lachnospiraceae, Akkermansia, and Sutterella, respectively.

CONCLUSIONS

These data suggest that AAP treatment is associated with specific representation of gut bacterial families in AAP-treated patients. In addition, AAP treatment is associated with decreased species richness in female AAP-treated patients.

摘要

目的

非典型抗精神病药物(AAP)类药物常与代谢性疾病相关,但这种风险的机制基础尚不清楚。由于有报道将肠道细菌功能与代谢性疾病联系起来,我们推测成人使用AAP治疗会导致肠道菌群失调,从而加重代谢指标。本报告描述了近期在一个双相情感障碍(BD)人类队列中,将AAP治疗与肠道微生物群落差异联系起来的研究结果。

方法

在一项横断面设计中,我们从117名BD患者(49名接受AAP治疗,68名未接受AAP治疗)中获取了16S核糖体序列。采用分子方差分析(AMOVA)检测组间微生物群落的显著聚类情况,并使用逆辛普森多样性指数计算α多样性。使用线性判别分析效应大小来检测组间差异丰富的可操作分类单元(OTU)。

结果

与未接受AAP治疗的患者相比,接受AAP治疗的队列明显更年轻,体重指数更高。除AAP队列中苯二氮䓬类药物的使用量较高外,两组在其他精神药物的使用上没有差异。我们检测到接受AAP治疗和未治疗患者的微生物群落之间存在显著分离(AMOVA;p = 0.04)。与未接受AAP治疗的女性相比,接受AAP治疗的女性物种多样性显著降低(p = 0.015)。男性在治疗组之间没有显著的多样性差异(p = 0.8)。治疗组之间差异丰富的OTU分别为OTU1、OTU25和OTU32,它们分别归类于毛螺菌科、阿克曼氏菌属和萨特氏菌属。

结论

这些数据表明,AAP治疗与接受AAP治疗患者肠道细菌家族的特定表现有关。此外,AAP治疗与接受AAP治疗的女性患者物种丰富度降低有关。

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