Gastrointestinal symptoms are associated with hypothalamic-pituitary-adrenal axis suppression in healthy individuals

The brain-gut axis has been proposed to influence symptoms in irritable bowel syndrome (IBS). In animal studies corticotropin-releasing hormone (CRH) challenge has been associated with decreased upper gastrointestinal motility and increased colonic motility. The purpose of this study was to investigate the association between gastrointestinal symptoms and the effect of CRH on the hypothalamic-pituitary-adrenal (HPA) axis using a weight-adjusted low-dose dexamethasone test in a group of healthy individuals (n = 157).

Pre- and post-dexamethasone morning serum cortisol was analysed. All participants completed questionnaires regarding symptoms of IBS (GSRS-IBS (Gastrointestinal Symptom Rating Scale-IBS) and symptoms of anxiety and depression (HADS (Hospital Anxiety and Depression Scale)). After exclusions, 124 subjects were available for analysis (F/M: 60/64, mean age 55.8 years, SD 15.4, range 21-80 years).

A positive correlation was found between the GSRS-IBS score and HADS score (rs =0.36; p <0.001). There was no linear correlation between either pre- (rs = 0.145; p = 0.11) or post-dexamethasone cortisol levels (rs =0.087; p =0.337) and GSRS-IBS scores. By subgrouping the subjects at the lower and higher 25th percentiles of their post-dexamethasone morning cortisol levels, we found a trend towards a higher GSRS-IBS score (median 7.0 versus 5.0; p =0.069) (multivariate adjusted OR 2.6; CI 0.80-8.3) and a significantly higher diarrhoea score (median 2 versus 0; p = 0.021) (multivariate adjusted OR 5.7; CI 1.5-22), and a higher early satiety score (p=0.008) (multivariate adjusted OR 6.7; CI: 1.9-23) in the subjects with high post-dexamethasone cortisol levels (low HPA suppression) compared with the subjects with intermediate post-dexamethasone cortisol levels. Furthermore, individuals with low post-dexamethasone cortisol levels (high HPA suppression) showed a significant, higher score for diarrhoea (median 2.0 versus 0; p =0.010) (multivariate adjusted OR 6.1; CI 1.8-20) and early satiety (p=0.076) (multivariate adjusted OR 3.2; CI 1.0-10) compared with those with intermediate cortisol levels.

A trend toward a non-linear relationship between IBS-like symptoms and post-dexamethasone cortisol levels was observed in healthy individuals, with significantly more symptoms of diarrhoea and early satiety in individuals with high or low post-dexamethasone cortisol levels in comparison with those with intermediate post-dexamethasone cortisol levels.