西班牙 Dr. Josep Trueta医院José Manuel Fernández-Real、Jordi Mayneris-Perxachs和庞培法布拉大学Rafael Maldonado研究组合作取得一项新成果。经过不懈努力，他们的研究发现与脯氨酸代谢相关菌群的改变会影响抑郁症。2022年5月3日，国际学术期刊《细胞-代谢》发表了这一成果。

研究人员运用一种多组学方法，将临床前模型与包括轻度抑郁症患者在内的三个类队列相结合。微生物功能和与谷氨酸/GABA代谢相结合的代谢物，特别是脯氨酸，与抑郁症有关。高脯氨酸摄入是对抑郁症影响最大的饮食因素。全脑动力学揭示了与抑郁症和脯氨酸循环相关的多样网络中断。在小鼠饮食中补充脯氨酸会加剧抑郁症以及微生物易位。

将人类微生物群移植入小鼠诱导了情绪受损的表型以及GABA、脯氨酸和细胞外基质相关的前额叶皮层基因的改变。RNAi介导的果蝇脯氨酸和GABA转运蛋白的敲低以及与高GABA生产者L. plantarum的单一关联，增加了对抑郁样状态的保护。靶向微生物组和改变膳食脯氨酸可能为有效治疗抑郁症打开新窗口。

据介绍，微生物-肠-脑通路已成为治疗抑郁症的新靶点，抑郁症是一种治疗效果不佳的疾病。然而，目前的研究主要集中在重度抑郁症上，而针对微生物组功能、成分性质或混杂因素的研究比较稀缺。

附：英文原文

Title: Microbiota alterations in proline metabolism impact depression

Author: Jordi Mayneris-Perxachs, Anna Castells-Nobau, María Arnoriaga-Rodríguez, Miquel Martin, Lisset de la Vega-Correa, Cristina Zapata, Aurelijus Burokas, Gerard Blasco, Clàudia Coll, Anira Escrichs, Carles Biarnés, José María Moreno-Navarrete, Josep Puig, Josep Garre-Olmo, Rafel Ramos, Salvador Pedraza, Ramón Brugada, Joan Carles Vilanova, Joaquín Serena, Jordi Gich, Lluís Ramió-Torrentà, Vicente Pérez-Brocal, Andrés Moya, Reinald Pamplona, Joaquim Sol, Mariona Jové, Wifredo Ricart, Manuel Portero-Otin, Gustavo Deco, Rafael Maldonado, José Manuel Fernández-Real

Issue&Volume: 2022/05/03

Abstract: The microbiota-gut-brain axis has emerged as a novel target in depression, a disorder with low treatment efficacy. However, the field is dominated by underpowered studies focusing on major depression not addressing microbiome functionality, compositional nature, or confounding factors. We applied a multi-omics approach combining pre-clinical models with three human cohorts including patients with mild depression. Microbial functions and metabolites converging onto glutamate/GABA metabolism, particularly proline, were linked to depression. High proline consumption was the dietary factor with the strongest impact on depression. Whole-brain dynamics revealed rich club network disruptions associated with depression and circulating proline. Proline supplementation in mice exacerbated depression along with microbial translocation. Human microbiota transplantation induced an emotionally impaired phenotype in mice and alterations in GABA-, proline-, and extracellular matrix-related prefrontal cortex genes. RNAi-mediated knockdown of proline and GABA transporters in Drosophila and mono-association with L. plantarum, a high GABA producer, conferred protection against depression-like states. Targeting the microbiome and dietary proline may open new windows for efficient depression treatment.

DOI: 10.1016/j.cmet.2022.04.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00128-0