There is a higher prevalence of functional GI disorders among obese and overweight children. However, the role of obesity in functional GI disorders, such as irritable bowel syndrome (IBS), in adults remains unclear. In a study that used CT scans to measure visceral adipose tissue (VAT) it was demonstrated that higher VAT is associated with IBS, especially IBS-diarrhea (IBS-D). This study did not examine the role of VAT in clinical outcomes such as symptom severity or quality of life.
Previous studies have demonstrated that both obesity and IBS5 are independently associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Animal studies have established a sex-dependent link between VAT inflammatory markers and HPA axis overactivity. Thus, VAT may contribute to the pathophysiology of IBS in a sex-dependent manner. The association of visceral adiposity with IBS, IBS symptom severity and HPA function, and the possible sex-dependent relationship, has not been studied.
This study determines if visceral adiposity is associated with (1) the presence of IBS and IBS bowel habit subtype, and the sex differences in these associations will be assessed; (2) symptom severity and quality of life (QoL) in those with IBS; and (3) alterations in the HPA axis in response to hormone challenge. Sex differences in these associations will be assessed.
Study Population IBS patients determined by Rome III criteria and healthy controls (HC) were recruited. All participants completed a number of questionnaires including the IBS symptom severity scale (IBS-SSS), IBS quality of life (IBS-QoL), and Hospital Anxiety and Depression Scale (HAD). All participants underwent a DXA scan to measure VAT, subcutaneous adipose tissue (SAT), and total adipose tissue (TAT). Obesity measures including body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) were collected as per World Health Organization standards.
Hormone Challenge The HPA axis response to stress was evaluated in a subgroup of participants (34 HC, 61 IBS). Cortisol and ACTH levels in response to corticotrophin releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) were measured.
Statistical Analysis Linear regression analysis was used to test the association of the measures of visceral adiposity with primary and secondary outcomes in IBS patients and healthy controls, while controlling for age, sex, and anxiety where appropriate.
A total of 138 subjects (45 HC, 93 IBS) were analyzed. Males consistently showed higher measures of abdominal obesity than females: VAT p=0.004, VAT/SAT ratio p<0.0001, VAT/TAT ratio p<0.0001, WC p=0.050, WHR p<0.001. This was not seen with the generalized obesity measure of BMI (p=0.094). Visceral adiposity (VAT p=0.690; VAT/SAT ratio p=0.428; VAT/TAT ratio p=0.497) was not associated with IBS diagnosis, IBS disease-related quality of life, symptom severity, or visceral sensitivity. VAT showed a significant association with IBS-constipation (p=0.014) when compared with HC. The association of VAT and IBS, although not statistically significant, shows a sex dependent trend. Among those with IBS, a hyper-responsive HPA axis is demonstrated and is positively associated with VAT, independent of age, sex, and anxiety.
Among IBS patients, there was no association between visceral adiposity and the diagnosis of IBS, symptom severity, or quality of life. However, VAT showed a sex-dependent association with IBS with IBS women demonstrating lower VAT compared to IBS men and HCs. Therefore, sex differences in the distribution of visceral adiposity may play a role in IBS pathophysiology. The mechanism of this may be linked to sex differences that have been shown in other studies of IBS including differences in pathophysiology, visceral pain, and diet.
Our results are consistent with previous studies showing a positive association between VAT and IBS-D. IBS-C is negatively associated with VAT in this study. This difference appears to be primarily due to sex differences and the fact that there are a higher proportion of women in the IBS-C group.
Cortisol response to ACTH increases with increasing VAT in IBS patients. The physiological mechanism may be due to altered microbiome, adipokine profile, and/or enzyme expression. Further studies are needed to better understand the mechanism of this finding.