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


 Gut microbiome dysbiosis is associated with the development of depression. Fecal microbiota transplantation (FMT) has been proposed as a potential therapeutic solution for depression. However, the efficacy of FMT to reduce depression is still unknown. 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; additionally, FH recipients showed a significant shift in the serum metabolome, but not the hippocampal metabolome. Co-occurrence analysis suggests that SD-FMT ameliorated recipients’ physiochemical features of depression by the metabolic modulation 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.