Abstract
Although alterations in the gut microbiota have been linked to the pathophysiology of major depressive disorder (MDD), including through effects on the immune response, our understanding is deficient about the straight connection patterns among microbiota and MDD in patients. Male and female MDD patients were recruited: 46 patients with a current active MDD (a-MDD) and 22 in remission or with only mild symptoms (r-MDD). Forty-five healthy controls (HC) were also recruited. Psychopathological states were assessed, and fecal and blood samples were collected. Results indicated that the inducible nitric oxide synthase expression was higher in MDD patients compared with HC and the oxidative stress levels were greater in the a-MDD group. Furthermore, the lipopolysaccharide (an indirect marker of bacterial translocation) was higher in a-MDD patients compared with the other groups. Fecal samples did not cluster according to the presence or the absence of MDD. There were bacterial genera whose relative abundance was altered in MDD: Bilophila (2-fold) and Alistipes (1.5-fold) were higher, while Anaerostipes (1.5-fold) and Dialister (15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of Alistipes and Anaerostipes (1.5-fold) and a complete depletion of Dialister compared with HC. Patients with r-MDD presented higher abundance of Bilophila (2.5-fold) compared with HC. Thus, the abundance of bacterial genera and some immune pathways, both with potential implications in the pathophysiology of depression, appear to be altered in MDD, with the most noticeable changes occurring in patients with the worse clinical condition, the a-MDD group.
Highlights
Inflammatory processes can be implicated in the development of depressive-like symptoms or major depressive disorder (MDD) [1,2,3]
Inflammation is linked with the clinical severity of mood disorders and remission of MDD is connected with the normalization of inflammatory markers [5, 6]
The abundance of sequences from the genera Bilophila and performed in cytosolic extracts, except for the two transcription Alistipes was higher in MDD patients (both MDD groups factors studied (i.e., NF-κBp65 and PPARγ), whose expression levels were analyzed in nuclear extracts compared with healthy controls (HC) (Fig. 1D, E)
Summary
Inflammatory processes can be implicated in the development of depressive-like symptoms or major depressive disorder (MDD) [1,2,3]. Clinical and psychopathological states were alterations could be a contributory factor to the development of assessed by means of the Spanish versions of the HDRS [31], the MDD [21] These alterations would increase the intestinal barrier Euroquol-5D visual analog scale (EQ-Vas, a measure of selfpermeability allowing a bacterial translocation [22], which could perceived health-related quality of life) [32], the perceived stress be related to the inflammatory hypothesis of depression [23]. Rome III criteria for functional gastrointestinal pathology inducing a neuroinflammatory response through TLR-4 activation [36] in the last 3 months were evaluated in all the groups by in the brain [24, 25] This scenario seems to happen in MDD means of a questionnaire (ten yes/no items) while the psycholopatients as well, suggesting that bacterial translocation would be gical assessments were performed. PCR amplification and sequencing. 16S rDNA gene amplicons were amplified following the Illumina protocol for 16S rDNA gene metagenomic sequencing library preparation
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