*Review* **Microbiota-Orientated Treatments for Major Depression and Schizophrenia**

**Guillaume B. Fond 1,\*, Jean-Christophe Lagier 2, Stéphane Honore 1, Christophe Lancon 1, Théo Korchia 1, Pierre-Louis Sunhary De Verville 1, Pierre-Michel Llorca 3, Pascal Auquier 1, Eric Guedj <sup>4</sup> and Laurent Boyer <sup>1</sup>**


Received: 7 February 2020; Accepted: 2 April 2020; Published: 8 April 2020

**Abstract:** 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.

**Keywords:** psychiatry; schizophrenia; depression; microbiota; transplantation
