Effects of ‘Healthy’ Fecal Microbiota Transplantation against the Deterioration of Depression in Fawn-Hooded Rats

• DOI: 10.1128/msystems.00218-22
• Publication Date: 2022-04-28T12:01:27Z
• Authors: Bing Hu; Promi Das; Xianglin Lv; Meng Shi; Jiye Aa; Kun Wang; Liping Duan; Jack A. Gilbert; Yong Nie; Xiao-Lei Wu
• Keywords: Metabolome; Gut–brain axis; Depression

Depression is a recurrent, heterogeneous mood disorder occurring in more than 260 million people worldwide. Gut microbiome dysbiosis associated with the development of depressive-like behaviors by modulating neuro-biochemical metabolism through microbiome-gut-brain (MGB) axis. Fecal microbiota transplantation (FMT) has been proposed as potential therapeutic solution for depression, but efficiency and mechanism are unknown. Here, we performed an FMT from Sprague-Dawley (SD) rats ('healthy' controls) to Fawn-hooded (FH) (depression model). Pre-FMT, FH exhibited significantly elevated distinct neurotransmitter cytokine levels compared SD rats. Post-FMT, recipients receiving fecal (FH-FH rats) showed aggravated behaviors, while ones (FH-SD had alleviated depressive symptoms, significant increase hippocampal neurotransmitters, decrease some cytokines FH-FH SD-FMT resulted FH-SD rats' gut resembling donors, shift serum metabolome not metabolome. Co-occurrence analysis suggests that prevented recipients' depression via microbial species such Dialister sp., which led metabolic modulation hippocampus enteric nervous system, intestinal barrier, blood-brain barrier. Our results provided new data pointing multiple mechanisms interaction impact on therapy. IMPORTANCE chronic, recurrent mental disease, could make patients commit suicide severe cases. Considering cause symptoms animals MGB axis, modification expected be therapy daily administration probiotics invalid or transient. In this study, demonstrated transferred healthy rat model regulate recipient's neurobiology behavior systematic alternation followed metabolism. These underline significance understanding disorders suggest 'healthy' function solve host's cerebral inflammation may serve novel strategy depression.