Altered Microbiome Signature in Cushing’s Syndrome Persists Beyond Remission

German Rubinstein, Ilias Lagkouvardos, Evangelia Intze, Andrea Osswald, Stephanie Zopp, Leah Theresa Braun, Adriana Albani, Heike Künzel, Anna Riester, Felix Beuschlein, Martin Reincke, Katrin Ritzel
The Journal of Clinical Endocrinology & Metabolism, Volume 110, Issue 9, September 2025, Pages 2615–2622
https://doi.org/10.1210/clinem/dgae887

Abstract

Context

Patients with Cushing's syndrome (CS) suffer from metabolic and cardiovascular comorbidities caused by hypercortisolism. The human gut microbiome responds to different pathological conditions.

Objective

The aim of our study was to analyze the effect of chronic endogenous cortisol excess on the gut microbiome.

Methods

We prospectively recruited 18 patients with endogenous CS of different etiologies (mainly pituitary CS, n = 13). Patients provided a stool sample during active CS and 1 to 2 years after successful surgical treatment being in biochemical remission. In addition, 36 patients, in whom CS was excluded, served as an obese control group and 108 samples from healthy lean students were used as a reference group. Amplicons of the V3/V4 region of the 16S ribosomal RNA gene, from every sample, were sequenced and clustered into operational taxonomic units. The microbial profiles of CS patients were then compared to the control and reference groups using R scripts.

Results

In comparison to lean references, the gut microbiome of patients with florid CS demonstrated a disturbed microbial profile. Microbial dysbiosis of patients with CS was maintained even after biochemical remission following curative surgery.

Conclusion

Patients with CS have a distinct and disturbed gut microbiome that persists even after surgery, indicating a possible target for additional probiotic interventions to accelerate convergence to a healthy microbiome.

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