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

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:<jats:italic>Bilophila</jats:italic>(2-fold) and<jats:italic>Alistipes</jats:italic>(1.5-fold) were higher, while<jats:italic>Anaerostipes</jats:italic>(1.5-fold) and<jats:italic>Dialister</jats:italic>(15-fold) were lower in MDD patients compared with HC. Patients with a-MDD presented higher relative abundance of<jats:italic>Alistipes</jats:italic>and<jats:italic>Anaerostipes</jats:italic>(1.5-fold) and a complete depletion of<jats:italic>Dialister</jats:italic>compared with HC. Patients with r-MDD presented higher abundance of<jats:italic>Bilophila</jats:italic>(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.