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

Background: Although the lack of estrogen receptor beta (ER beta) 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 ER beta-deficient mice. Results: In response to dextran sodium sulfate (DSS) insult, the ER beta knockout mice displayed significant shift in alpha and beta 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 ER beta-deficient mice, which was associated with colitis and anxiety-like behaviors. In addition, RNA sequencing data suggested that ErbB4 might be the target of ER beta 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: ER beta has the potential to inhibit colitis development and anxiety-like behaviors via remodeling of the gut microbiota, which suggests that ER beta is a promising therapeutic target for the treatment of IBD and related anxiety-like behaviors.

Automated summary

The gut microbiota plays a critical role in mediating the development of colitis and anxiety-like behaviors. Lack of ER beta leads to changes in the gut microbiota composition, exacerbating colitis and anxiety-like behaviors. Remodeling of the gut microbiota can inhibit the development of colitis and anxiety-like behaviors.