Inflammatory processes have been linked to depressive illness, possibly being driven by stressful experiences. As well changes in the balance between microbial species compromising the microbiome could be important in precipitating cytokines and other inflammatory factors that, in turn, influence several pathways leading to depression. In particular, hormonal (e.g. glucocorticoids), trophic (e.g. reductions of growth factors) and oxidative stress signaling in the brain can be altered by the inflammatory milieu, including excessive cytokine release, which contribute to the symptoms that characterize a depressed state (e.g. anhedonia, lethargy, disturbed feeding). Identifying the ‘signature’ of inflammatory changes evident in the microbiome of specific depressed patients could yield important biomarkers to guide the development of personalized approaches to treatment.