Gut microbiota, innate immune pathways, and inflammatory control mechanisms in patients with major depressive disorder.

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.

The role of PPARgamma on restoration of colonic homeostasis after experimental stress-induced inflammation and dysfunction.

BACKGROUND & AIMS: Psychological stress has been implicated in the clinical course of several gastrointestinal diseases, but the mechanisms implicated and the effects of stress on the normal colon are not yet fully understood. METHODS: Male Wistar rats were exposed to various immobilization periods as a stress paradigm. Colon was processed to assess myeloperoxidase activity, nitric oxide synthase 2, cyclooxygenase 2, and peroxisome proliferator-activated receptor gamma (PPARgamma) expression and production of prostaglandins. Colonic permeability, bacterial translocation, tight junctions ultrastructure, and immunoglobulin (Ig) A levels were also evaluated. RESULTS: Exposure to acute (6 hours) immobilization stress produced an increase in myeloperoxidase activity and nitric oxide synthase 2 and cyclooxygenase 2 expression. All these parameters remained increased after 5 days of repeated stress exposure, showing a trend to normalize after 10 days. Levels of the anti-inflammatory eicosanoid 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) and expression of PPARgamma run parallel with these changes. Colonic epithelial barrier was altered after stress exposure, and a significant decrease in colonic IgA levels after acute stress exposure was observed. Pretreatment with PPARgamma agonists 15d-PGJ(2) and rosiglitazone prevented colonic inflammation and barrier dysfunction as well as the decrease of IgA production induced after acute stress; PPARgamma specific antagonist T0070907 reverted these effects. CONCLUSIONS: Activation of PPARgamma in rat colon in vivo seems to counteract colonic inflammation and dysfunction induced by stress. On the other hand, PPARgamma ligands may be therapeutically useful in conditions in which inflammation and barrier dysfunction takes place in colon after exposure to stress.