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

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

doi:10.3389/fnut.2021.805465

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

Front Nutr. 2022 Jan 26:8:805465. doi: 10.3389/fnut.2021.805465. eCollection 2021.

Authors

Furong Huang^{1

2}, Xiujie Liu³, Sheng Xu⁴, Sitao Hu¹, Sisi Wang³, Dibang Shi⁴, Kaicheng Wang², Zhongxiang Wang¹, Qiongqiong Lin⁴, Shan Li³, Siyuan Zhao³, KeKe Jin³, Chuang Wang⁵, Lei Chen¹, Fangyan Wang³

Affiliations

¹ Department of Orthopaedics, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Key Laboratory of Intelligent Critical Care and Life Support Research of Zhejiang Province, Wenzhou, China.
³ School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.
⁴ The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
⁵ Department of Pharmacology, Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, China.

Abstract

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&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.

Keywords: BDNF; Prevotella histicola; depression; inflammation; microbiota; tight junction protein.