Microbiota-Orientated Treatments for Major Depression and Schizophrenia.

BACKGROUND AND SIGNIFICANCE: There is a need to develop new hypothesis-driven treatment for both both major depression (MD) and schizophrenia in which the risk of depression is 5 times higher than the general population. Major depression has been also associated with poor illness outcomes including pain, metabolic disturbances, and less adherence. Conventional antidepressants are partly effective, and 44% of the subjects remain unremitted under treatment. Improving MD treatment efficacy is thus needed to improve the SZ prognosis. Microbiota-orientated treatments are currently one of the most promising tracks. METHOD: This work is a systematic review synthetizing data of arguments to develop microbiota-orientated treatments (including fecal microbiota transplantation (FMT)) in major depression and schizophrenia. RESULTS: The effectiveness of probiotic administration in MD constitutes a strong evidence for developing microbiota-orientated treatments. Probiotics have yielded medium-to-large significant effects on depressive symptoms, but it is still unclear if the effect is maintained following probiotic discontinuation. Several factors may limit MD improvement when using probiotics, including the small number of bacterial strains administered in probiotic complementary agents, as well as the presence of a disturbed gut microbiota that probably limits the probiotics' impact. FMT is a safe technique enabling to improve microbiota in several gut disorders. The benefit/risk ratio of FMT has been discussed and has been recently improved by capsule administration. CONCLUSION: Cleaning up the gut microbiota by transplanting a totally new human gut microbiota in one shot, which is referred to as FMT, is likely to strongly improve the efficacy of microbiota-orientated treatments in MD and schizophrenia and maintain the effect over time. This hypothesis should be tested in future clinical trials.

The gastrointestinal tract microbiome, probiotics, and mood.

Mental health is closely linked to physical health. Depression (e.g., major depression) is highly prevalent worldwide and a major cause of disability. In a subgroup with treatment-resistant depression, standard pharmacotherapy interventions provide small if any incremental improvement in patient outcomes and may also require the application of an alternate approach. Therefore, in addition to the standard pharmacotherapies prescribed, patients will also be advised on the benefits of psychological counseling, electroconvulsive therapy, and transcranial magnetic stimulation or increasing physical activity and reducing harmful substance consumption. Numerous nutraceuticals have a beneficial role in treatment-resistant depression and include, herbal medicines of which Hypericum perforatum is the best studied, omega-3 fatty acid preparations, S-Adenosyl-L-Methionine (SAMe), various mineral formulations (e.g., magnesium) and folate (singly or in combination with B group vitamins) are prescribed to a lesser extent. Furthermore, a largely neglected area of research activity has been the role of live probiotic cultures that contribute to repairing dysbiosis (a leaky gut barrier abnormality) in the gastrointestinal tract (GIT). In this commentary, we build a hypothesis that in addition suggests that GIT metabolites that are elaborated by the microbiome cohort may provide novel and significant avenues for efficacious therapeutic interventions for mood disorders. We posit that the microbiome in the gastrointestinal tract is implicit as an important participant for the amelioration of adverse mood conditions via the diverse metabolic activities provided by live beneficial bacteria (probiotics) as an active adjuvant treatment. This activity is in part triggered by a controlled release of reactive oxygen species (ROS) and hence further questions the antioxidant/oxidative stress postulate.