Amelioration of depressive symptoms on Fawn-Hooded rats through the 'healthy' fecal microbiota transplantation

Abstract

Background : Depression is a recurrent, heterogeneous mood disorder, occurring in more than 260 million people worldwide. Gut microbiome dysbiosis is associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through the microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression, but the therapeutic efficiency and mechanism is unknown. Results : We performed FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) rats (depression model). Pre-FMT, the FH rats exhibited significantly elevated depressive behaviors and distinct neurotransmitter and cytokine levels compared with SD rats. Post-FMT, FH recipients receiving SD microbiota showed reduced depressive behaviors, a significant increase in hippocampal neurotransmitters and a significant decrease of some hippocampal cytokines compared to the ones receiving FH microbiota. SD-FMT resulted in the FH recipients' gut microbiome resembling the SD donor, and a significant shift in the serum metabolome but not the hippocampal metabolome. Conclusions : SD-FMT was inferred to ameliorate recipients' physiochemical features of depression via the significant decrease of gut microbial species such as Dialister sp., which led to the recipients' metabolic modulation in serum and hippocampus through the enteric nervous system, the intestinal barrier and the blood-brain barrier. Our results provided new data pointing to multiple mechanisms of interaction for the impact of gut microbiome modulation on depression therapy.