Probiotic Bifico Ameliorates Depression- and Anxiety-Like Behaviors Induced by Estrogen Deficiency via NLRP3 Inflammasome Inhibition.

PURPOSE: Dysregulation of the microbiota-gut-brain (MGB) axis and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome are implicated in estrogen deficiency induced depression and anxiety disorders. This study aims to investigate the effects of the probiotic Bifico on neuroinflammation and behaviors in ovariectomized (OVX) rats. METHODS: After OVX rats were treated with Bifico for 6 weeks, depression- and anxiety-like behaviors were evaluated using the sucrose preference test, forced swimming test, open field test and elevated plus maze. Furthermore, 16S rRNA sequencing was used to analyze changes in gut microbiota. Hematoxylin-eosin (HE) staining was used to observe the changes in tissue structure (intestinal tissue and hippocampus). Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory factors. Western blot was used to detect tissue protein levels. RESULTS: The treatment of Bifico for 6 weeks can ameliorate depression- and anxiety-like behaviors induced by estrogen deficiency. In addition, Bifico increased the abundance of gut microbiota, especially Lactobacillus sp. and Desulfovibrio, and significantly ameliorated histological injuries in the ileum, colon and hippocampus. Bifico up-regulated the expression of tight-junction proteins zona occludens 1 (ZO-1) and Occludin in the colon and hippocampus, and down-regulated the expression of NLRP3 inflammasome signaling pathway-related proteins, including NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, interleukin (IL)-1β, IL-18, toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated (P)-P65 and P65. Meanwhile, Bifico also reduced the levels of IL-6 and tumor necrosis factor (TNF)-α in serum and hippocampus. CONCLUSION: Our findings suggest that probiotics ameliorate the depression- and anxiety-like behaviors in OVX rats by alleviating gut microbiota dysbiosis and reduce gut inflammation, thereby dampening neuroinflammation via inhibition of the NLRP3 inflammasome signaling pathway in the hippocampus. Therefore, NLRP3 inflammasome activation mediated by the MGB axis may be a potential therapeutic target for estrogen deficiency-induced affective disorders.