Research on the effects of long-term exposure to high cortisol concentrations on immune-inflammatory responses and microbiota-gut-brain axis based on a model of Cushing's disease
XU Junpeng
ZHANG Yanyang
ZHOU Tao
WANG Peng
FENG Zhebin
SHANG Guosong
SUN Yuxiang
MAO Zhiqi
YU Xinguang
ZHANG Jianning
Abstract：Objective To explore the effects of long-term exposure to high cortisol concentrations on human inflammatory response and microbiota-gut-brain axis by using Cushing's disease(CD)as a model.Methods We prospectively included 16 CD patients who were to be operated from May 2021 to March 2024 in the Chinese PLA General Hospital,and recruited 30 healthy controls(HC)during the same period.We compared the differences in neuropsychological and cognitive function scores,inflammatory factors,and gut microbiota between the two groups.Results Our study results showed that the average course of disease of CD patients was(55.75±39.96)months,and the levels of serum cortisol,adrenocorticotropic hormone,24-hour urinary cortisol excretion,and body mass index were significantly higher than those in HC group(P＜0.05).Neuropsychological and cognitive function scale data showed that the scores of Self-Rating Depression Scale and Self-Rating Anxiety Scale in CD patients were significantly higher than those in HC group,while the scores of Mini-Mental State Examination and Montreal Cognitive Assessment were lower than those in HC group(P＜0.000 1).The differences in gut microbial ecology structure between CD patients and HC group included decreased microbial diversity and significant differences at the species and genus levels.Analysis of blood and immunological indicators showed that the white blood cell count,neutrophil proportion,NLR,and levels of IL-1β and IL-8 in CD patients were higher,while the eosinophils proportion was lower(P＜0.05),and the levels of IL-6 and TNF were not significantly different.Conclusion High cortisol concentrations can increase the risk of obesity,cause anxiety and depression,and reduce cognitive function.In addition,it can also cause inflammatory responses,reduce immune function,and lead to changes in the composition and structure of gut microbiota and decreased diversity.
Keywords：cortisolCushing's diseasegut microbiotainflammatory responseneuropsychologyhypothalamic-pituitary-adrenal axismicrobiota-gut-brain axis
Publication Date：2025-03-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：6( 344-348,356 )