Journal Article

Estrogen receptor β deficiency impairs gut microbiota: a possible mechanism of IBD-induced anxiety-like behavior

Cai, Yun, Wang, Lian, Zou, Jiao, Xu, Xingshun, Ma, Yuanyuan, Zhao, Jinghui, Gustafsson, Jan-Ake, Li, Xin, Margaret, Warner, Fan, Xiaotang, Xiao, Rui, Gao, Junwei, Wang, Zhongke, Xu, Haiwei, Kong, Anqi, Xie, Ruxin, Yang, Ling, Liu, Tianyao

2022

Overview

Background Although the lack of estrogen receptor β (ERβ) is a risk factor for the development of inflammatory bowel disease (IBD) and psychiatric disorders, the underlying cellular and molecular mechanisms are not fully understood. Herein, we revealed the role of gut microbiota in the development of IBD and related anxiety-like behavior in ERβ-deficient mice. Results In response to dextran sodium sulfate (DSS) insult, the ERβ knockout mice displayed significant shift in α and β diversity in the fecal microbiota composition and demonstrated worsening of colitis and anxiety-like behaviors. In addition, DSS-induced colitis also induced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in ERβ-deficient mice, which was associated with colitis and anxiety-like behaviors. In addition, RNA sequencing data suggested that ErbB4 might be the target of ERβ that is involved in regulating the HPA axis hyperactivity caused by DSS insult. Gut microbiota remodeling by co-housing showed that both the colitis and anxiety-like behaviors were aggravated in co-housed wild-type mice compared to single-housed wild-type mice. These findings suggest that gut microbiota play a critical role in mediating colitis disease activity and anxiety-like behaviors via aberrant neural processing within the gut-brain axis. Conclusions ERβ has the potential to inhibit colitis development and anxiety-like behaviors via remodeling of the gut microbiota, which suggests that ERβ is a promising therapeutic target for the treatment of IBD and related anxiety-like behaviors. FTXHXyuG-24pgeg6Vx5ybR Video Abstract

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Anxiety / Behavior / Bioinformatics / Biomedical and Life Sciences / Biomedicine / Colitis / Colon / Crohn's disease / Development and progression / Dextran / Drinking water / ErbB-2 protein / ErbB4 / Estrogen / Estrogen receptor β / Estrogen receptors / Estrogens / Experiments / Fecal microflora / Feces / Gastrointestinal diseases / Gender differences / Gut microbiota / Gut-brain axis / Homeostasis / Hyperactivity / Hypothalamic-pituitary-adrenal axis / Hypothalamus / Inflammatory bowel disease / Inflammatory bowel diseases / Information processing / Intestinal microflora / Medical Microbiology / Medical research / Mental depression / Mental disorders / Mental health / Mental illness / Microbial Ecology / Microbial Genetics and Genomics / Microbiology / Microbiota / Microbiota (Symbiotic organisms) / Molecular modelling / Phenols / Pituitary / Risk factors / RNA sequencing / Sodium sulfate / Sulfates / Therapeutic targets / Virology