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Background  Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation.  Prevotella histicola  ( P. histicola ), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of  P. histicola  and clarify its potential mechanisms.    Methods  Mice were treated with  P. histicola  and cohousing after ovariectomy (OVX). The changes in depression-like behaviors among mice were examined by behavioral tasks, and alterations in the microbiota were detected through 16S rRNA sequencing. Changes in neuronal injury, protein synthesis, inflammatory factors, intestinal permeability, and nerve proliferation were observed by H&amp;amp;E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence.    Results   P. histicola  significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally,  P. histicola  significantly increases the abundance of intestinal flora, especially  Lactobacillus  and  Akkermansia . Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice.  P. histicola  was also found to upregulate tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the ileum and colon and reduce the levels of inflammatory factors VCAM, MCP-1, IL-6, IL-8, and TNF-α, mainly in the ileum, colon, and decrease the expression of COX-2, TLR4, Myd88, JNK, MCP-1, IL-6, IL-8, and TNF-α in the hippocampus. Moreover, significant downregulation of apoptosis (caspase-3 and caspase-8) and upregulation of neurotrophic factors (BDNF and Ki-67) were observed after  P. histicola  treatment.    Conclusion  Our data show that  P. histicola  significantly mitigates depression of OVX mice through improvement in intestinal microbiota to repair intestinal leakage and inhibit central inflammation to promote the expression of BDNF for hippocampal neurogenesis.  P. histicola  may be therapeutically beneficial for PMD.

Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice