Metabolism and Major Depression: Blood microbiome and metabolome exploration

Response to antidepressant is associated with blood microbiome and metabolome of patients with major depressive episodes (MDE)

In this article, Ciocan and colleagues explored the blood microbiome and metabolome in patients with major depressive episodes (MDE) before and after treatment and compared them to healthy controls.

→ The importance of the gut-brain axis is now very well-known and gut microbiota dysbiosis has been associated with neurodegenerative and mood disorders.

→ Gut microbiota dysbiosis is also known to exaggerate bacterial translocation from the gut to the bloodstream.

→ Using multi-omics, blood microbiome and metabolome were explored in patients with major depressive episodes (MDE) before and after treatment and compared to healthy controls.

→ Related to healthy controls, patients with MDE had a distinct blood microbiome with bacterial taxa previously associated with mood disorders or alcohol dependence, and a unique metabolomic signature (cyanoaminoacid and tryptophan metabolism)

→ Blood microbiome and metabolome changed after antidepressant treatment, and these changes depended on antidepressant treatment response.

→ Blood microbiome could be a new therapeutic target and prognostic tool for the treatment of patients experiencing a major depressive episode.

CITATIONS

Tissue microbiomes_1

Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case–control study

Ciocan D, Cassard AM, Becquemont L, Verstuyft C, Voican CS, El Asmar K, Colle R, David D, Trabado S, Feve B, Chanson P, Perlemuter G, Corruble E. J Psychiatry Neurosci. 2021 May 19;46(3):E358-E368. doi: 10.1503/jpn.200159. PMID: 34008933; PMCID: PMC8327971.

The microbiota interacts with the brain through the gut–brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment.

In this case–control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry.

The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment.

Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results.

Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode.

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