Microbiota alterations in proline metabolism impact depression

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...

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Bibliographic Details
Authors: Mayneris Perxachs, Jordi, Castells Nobau, Anna, Arnoriaga Rodríguez, María, Martín Sánchez, Miquel, Vega-Correa, Lisset de la, Zapata-Tona, Cristina, Burokas, Aurelijus, Blasco Solà, Gerard, Coll-Martinez, Clàudia, Escrichs, Anira, Biarnés, Carles, Moreno Navarrete, José María, Puig Alcántara, Josep, Garre Olmo, Josep, Ramos Blanes, Rafel, Pedraza, S., Brugada, Ramon, Vilanova, Joan Carles, Serena, Joaquín, Gich Fullà, Jordi, Ramió i Torrentà, Lluís, Pérez Brocal, Vicente, Moya, Andrés, Pamplona, Reinald, Sol, Joaquim, Jové, Mariona, Ricart, Wifredo, Portero Otin, Manuel, Deco, Gustavo, Maldonado, Rafael, Fernández-Real Lemos, José Manuel
Format: article
Status:Published version
Publication Date:2022
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10256/24504
Online Access:http://hdl.handle.net/10256/24504
Access Level:Open access
Keyword:Depressió psíquica
Mental depression
Intestins -- Microbiologia
Intestines -- Microbiology
Description
Summary: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

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