The gut microbiome in patients with Cushing's disease affects depression- and anxiety-like behavior in mice.

Background: Depression and anxiety significantly impact the quality of life in individuals with Cushing's disease (CD), which originates from pituitary neuroendocrine tumors (PitNETs), yet our understanding of the underlying mechanisms is limited. There is substantial evidence linking gut microbes to depression, anxiety, and endocrinology.

Results: The gut bacterial phenotype of patients with Cushing's disease was significantly different from that of the control group, and when the mice were treated with fecal bacteria from these patients, both anxiety- and depression-like behavior were significantly increased. However, this effect can be alleviated by supplementing with 2-(14, 15-epoxyeicosatrienoyl) glycerol (2-14,15-EG) which was found at reduced levels in the peripheral blood of mice treated with coprofecal bacteria from Cushing's disease. In this process, the effects of hormone levels and immune factors were not significant. In addition, in an animal model, corticosterone has been observed to affect behavioral changes in mice through gut microbiota composition, clarifying the cause-and-effect relationship between hormones, microbiota, and behavior. Finally, there was no significant difference in gut microbiome composition and its effects on mouse behavior in patients with Cushing's disease with different levels of depression and anxiety.

Conclusions: In summary, this research enhances our current understanding of how gut microbes in patients with Cushing's disease contribute to depression and anxiety, offering novel insights for clinical treatment approaches. Video Abstract.