Major depression is a highly prevalent, debilitating stress-related disorder and is recognized globally as one of the significant causes of disability, with considerable social consequences. The most consistently demonstrated abnormality in depressed patients is hypothalamic–pituitary–adrenal (HPA) axis dysregulation, manifested as elevated cortisol and corticotropin releasing factor (CRF). Furthermore, significant increases in the plasma concentrations of pro-inflammatory cytokines are usually observed.

Microbes exert a major influence on both the HPA axis and on the immune system, compounding the link between the microbiota and the stress response. Sudo and colleagues [5] were the first to demonstrate that germ-free mice who grew up in a sterile environment have an exaggerated HPA axis response to an acute stressor. It is noteworthy that this enhanced responsivity of the HPA axis can be reversed by monoassociation with a single bacterial strain, in this case Bifidobacterium infantis. Published studies in rodents indicate that treatment with this probiotic does impact on central neurotransmitter functioning.

A number of years ago, together with Bienenstock and colleagues at MacMaster University [6], we examined the impact of a Lactobacillus rhamnosus strain (JB-1) on anxiety- and antidepressant-related behavior, in addition to neurochemical changes in mice. L. rhamnosus-treated animals had lower levels of anxiety on a variety of behavioral measures, which was concomitant with alterations in the expression of both GABA A and GABA B receptors across a variety of brain regions studied. Yet the question remained as to how a dietary intake of a bacterial strain could alter brain and behavior. One possible route of communication is via the vagus nerve. To test this, animals underwent vagotomy or sham surgery and were subsequently treated with L. rhamnosus or an inactive control broth. Indeed, vagotomy prevented the behavioral and neurochemical effects of the potential probiotic strain, suggesting that L. rhamnosus could serve as a potential antidepressant/anxiolytic via its (or one of its metabolites) effects on the vagus nerve. Studies are currently underway to examine the effect of this microbe on stress responses in humans; preliminary results should be available shortly.

In what is the largest study of the microbiome in major depressive disorders to date, Jiang and colleagues [7] analyzed fecal samples from 46 patients with major depression and 30 healthy controls. The authors showed that patients with depression could be stratified according to their microbiome; acutely depressed patients had higher levels of Bacteroidetes, Proteobacteria and Actinobacteria, whereas levels of Firmicutes were significantly reduced. A negative correlation was observed between Faecalibacterium and the severity of depressive symptoms. This study needs replication and further additional questions need to be answered. Are there microbes that confer a resilience against depression and are there microbes that have a melancholic impact? Assuming microbes influence mood, through which mechanisms do they produce their effects?