AUTHOR=Huang Furong , Liu Xiujie , Xu Sheng , Hu Sitao , Wang Sisi , Shi Dibang , Wang Kaicheng , Wang Zhongxiang , Lin Qiongqiong , Li Shan , Zhao Siyuan , Jin KeKe , Wang Chuang , Chen Lei , Wang Fangyan 

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

JOURNAL=Frontiers in Nutrition

VOLUME=8

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2021.805465

DOI=10.3389/fnut.2021.805465

ISSN=2296-861X

ABSTRACT=<sec><title>Background</title><p>Estrogen deficiency-induced depression is closely associated with an imbalance in intestinal microbiota and inflammation. <italic>Prevotella histicola</italic> (<italic>P. histicola</italic>), an emerging probiotic, apparently improves inflammatory responses. This study aims to verify the antidepressant-like effects of <italic>P. histicola</italic> and clarify its potential mechanisms.</p></sec><sec><title>Methods</title><p>Mice were treated with <italic>P. histicola</italic> 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;E, Nissl staining, qRT-PCR, western blotting, and immunofluorescence.</p></sec><sec><title>Results</title><p><italic>P. histicola</italic> significantly reduces depression-like behaviors and neuronal damage induced by estrogen deficiency. Additionally, <italic>P. histicola</italic> significantly increases the abundance of intestinal flora, especially <italic>Lactobacillus</italic> and <italic>Akkermansia</italic>. Meanwhile, the cohoused mice also had a better emotional state and neutral structure compared with OVX mice. <italic>P. histicola</italic> 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 <italic>P. histicola</italic> treatment.</p></sec><sec><title>Conclusion</title><p>Our data show that <italic>P. histicola</italic> 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. <italic>P. histicola</italic> may be therapeutically beneficial for PMD.</p></sec>