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

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

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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. [MediaObject not available: see fulltext.].

Original languageEnglish (US)
Article number160
Issue number1
StatePublished - Dec 2022


  • Anxiety
  • ErbB4
  • Estrogen receptor β
  • Gut microbiota
  • Hypothalamic-pituitary-adrenal axis
  • Inflammatory bowel disease
  • Stress

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)


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