Cell子刊:菌群+饮食没“管好”,升脯氨酸致抑郁
创作:617 审核:617 2022年06月01日
  • 饮食来源的脯氨酸(Pro)和血液中的Pro水平与抑郁程度呈正相关;
  • 不同抑郁程度的患者肠道菌群的组成和功能不同,且肠道菌群会对循环Pro水平产生影响;
  • 脑铁沉积以及多个与rich-hub相关的脑部区域与抑郁程度或Pro水平相关;
  • 队列数据和小鼠实验表明,编码Pro和GABA转运蛋白的基因与抑郁症相关;
  • 果蝇实验表明,神经元中Pro和GABA转运蛋白的低表达可抵抗机械应激诱导的抑郁状态;
  • 给果蝇单一定植GABA高效生产者植物乳杆菌可抵抗抑郁状态。
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抑郁症是一种常见的精神障碍,影响了全球超过3亿人。近年来的研究表明,抑郁症患者的肠道菌群与健康人显著不同。这项来自于西班牙José Manuel Fernández-Real和Rafael Maldonado团队的研究利用3个队列的数据,结合多组学分析手段以及小鼠和果蝇实验,深入探究了微生物组与抑郁症的关系,揭示了依赖于微生物组的脯氨酸代谢变化对抑郁症的影响,强调了脯氨酸-谷氨酸-GABA-微生物组互作在抑郁症中的重要性。同时,该研究还提示我们减少饮食来源的脯氨酸和促进产GABA的肠菌或可有效改善抑郁情况。该研究的工作量和数据量非常大,值得大家仔细阅读原文。
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Cell Metabolism [IF:31.373]

Microbiota alterations in proline metabolism impact depression

依赖于菌群的脯氨酸代谢会影响抑郁症

10.1016/j.cmet.2022.04.001

2022-05-03, Article

Abstract & Authors:展开

Abstract:收起
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.

First Authors:
Jordi Mayneris-Perxachs

Correspondence Authors:
Jordi Mayneris-Perxachs,Rafael Maldonado,José Manuel Fernández-Real

All Authors:
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

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