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: 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.

Effect of Probiotics on Psychiatric Symptoms and Central Nervous System Functions in Human Health and Disease: A Systematic Review and Meta-Analysis

“…Immune defense via unspecific mechanisms along with the gut-associated lymphoid tissue are essential in this interplay. Furthermore, the immune-modulating potential of the GI microbiota [ 5 ] and some probiotics has been reported [ 6 ]. However, the interactions between the indigenous microorganisms and the host are mostly beneficial.…”

“…The former are important for the maintenance of the gut barrier function but also the overall health of the host [ 7 , 8 ]. Interestingly, the composition of the gut microbiota is different in patients with severe and moderate major depression disorder in comparison to healthy individuals [ 5 ]. In line with this, the gut microbiota can exert effects on central nervous system (CNS) functions via the microbiota–gut–brain axis, which has been extensively reviewed elsewhere [ 9 , 10 , 11 ].…”

Toward a Deeper Understanding of Gut Microbiome in Depression: The Promise of Clinical Applicability

“…These main findings are similar to several other human conditions which are linked to systemic and gut inflammation, and further confirm the inflammatory hypothesis of depression. Depression‐related gut microbial dysbiosis causes changes in the inflammatory markers, [ 57 ] and conversely, the activation of pro‐inflammatory responses can indirectly induce bacterial translocation that can participate in the pathophysiology of depression. [ 58 , 59 ] In brief, gut‐derived systemic inflammation is a driver of depression.…”

Alterations of the Gut Microbiome in Chinese Zhuang Ethnic Patients with Sepsis

“…Based on the abundance of these microbes, patients could be effectively classified as healthy individuals or patients with sepsis using an SVM algorithm. Among the four increased genera, Bilophila can produce lipopolysaccharides to stimulate the immune system via TLR-4 [30]. Porphyromonas gingivalis can regulate host innate immune signaling and induce inflammation [31].…”