Endocrine Abstracts

Background: Patients with Cushing’s syndrome (CS) in remission show residual cardiometabolic derangements leading to increased cardiovascular risk. Impaired characteristics of gut microbiome (dysbiosis), such as richness, diversity and composition, have been associated with several cardiometabolic risk factors, including obesity, insulin resistance and atherosclerosis. Whether CS patients present with intestinal dysbiosis is currently unknown. Our study was aimed at evaluating the relationship between the characteristics of gut microbiome and both body composition indexes and cardiometabolic risk factors in “cured” CS.

Methods: Twenty-seven female non-diabetic patients with CS in remission [mean (±SD) age, 51±9 years, mean (±SD) BMI, 26±3.8, median (IQR) duration of remission, 11(4) years] and 27 gender-, age-, and BMI-matched controls were included. Genomic DNA was extracted from fecal samples. The V4 region of the bacterial 16S rDNA was amplified by PCR, and sequencing was applied to analyze microbial richness (alpha diversity; Chao 1 index, observed number of species, effective Shannon index) and microbial community structure (beta diversity analysis through the Principal Coordinates Analysis (PCoA) of weighted and unweighted UniFrac distances). Inter-group difference in microbiome composition was analysed using ANCOM (Analysis of Composition of Microbiomes), a plugin from the QIIME2 pipeline. Lipid and coagulation profiles, fasting glycemia and fasting insulin were assessed using standard assays. Body composition was measured using dual-energy x-ray absorptiometry (DXA).

Results: The Chao 1 index was significantly lower in CS patients as compared with controls (Kruskal-Wallis test, q = 0.002), indicating that the former had lower microbial richness. Beta diversity analysis showed that fecal samples from CS patients clustered together and separated from the control samples (Adonis test, P<0.05). The Analysis of Composition of Microbiomes showed that several microbial groups at phylum, family, order and genus categories were associated with CS. In particular, Collinsella, a form genus of the Actinobacteria phylum, was present in all CS patients but not in controls. In CS, the Chao 1 index was associated with fibrinogen levels (ρ=0.44; P=0.034), and inversely correlated with both triglyceride concentrations (ρ=-0.48; P=0.035) and the HOMA-IR index (ρ=-0.45; P=0.038).

Conclusions: Patients with CS in remission have gut microbial dysbiosis with decreased microbiota richness and diversity, and specific variations in the bacterial community structure. Dysbiosis in CS may be one of the mechanisms whereby cardiometabolic dysfunctions persist after “cure”.