Study Links Depression with High Levels of the Amino Acid prolin

Good news! Are we finally coming closer to better treatment options?

"A growing body of literature ties the gut microbiome to symptoms of depression in a seemingly circular relationship where each affects the other. However, many of the studies on this relationship merely link certain bacterial populations or diets to major depressive disorder—leaving open critical questions about the underlying mechanisms of how the gut microbes might influence depression.

Research published last month (May 3) in Cell Metabolism takes an important step toward filling such gaps, demonstrating in multiple animal species that there is likely a causative relationship between depression severity and serum levels of the nonessential amino acid proline, which the study finds depend on both diet and the activity of proline-metabolizing bacteria in the gut. ..."

From the 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."

Study Links Depression with High Levels of an Amino Acid | The Scientist  Magazine® Experiments in animals and observations in humans suggest that the amount of proline circulating in one’s plasma has a strong association with depression severity.

Microbiota alterations in proline metabolism impact depression (open access)