Microbiota alterations in proline metabolism impact depression

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2022Author
Mayneris Perxachs, Jordi
Castells Nobau, Anna
Arnoriaga Rodríguez, María
Martin, Miquel
de la Vega Correa, Lisset
Zapata, Cristina
Burokas, Aurelijus
Blasco Solà, Gerard
Coll, Claudia
Escrichs, Anira
Biarnés, Carles
Moreno Navarrete, José María
Puig, Josep
Garre Olmo, Josep
Ramos, Rafel
Pedraza, Salvador
Brugada, Ramon
Vilanova, Joan Carles
Serena, Joaquín
Gich, Jordi
Ramió Torrentà, Lluís
Pérez Brocal, Vicente
Moya, Andrés
Sol, Joaquim
Ricart, Wifredo
Deco, Gustavo
Maldonado, Rafael
Fernández Real, José Manuel
Suggested citation
Mayneris Perxachs, Jordi;
Castells Nobau, Anna;
Arnoriaga Rodríguez, María;
Martin, Miquel;
de la Vega Correa, Lisset;
Zapata, Cristina;
...
Fernández Real, José Manuel.
(2022)
.
Microbiota alterations in proline metabolism impact depression.
Cell Metabolism, vol. 34, núm. 5, p. 681-701.
https://doi.org/10.1016/j.cmet.2022.04.001.
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Show full item recordAbstract
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 ad-
dressing 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 pro-line 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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Cell Metabolism, vol. 34, núm. 5, p. 681-701European research projects
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