Relationship between sympathoadrenal and pituitary-adrenal response during colorectal distention in the presence of corticotropin-releasing hormone in patients with irritable bowel syndrome and healthy controls

<div><p>Corticotropin-releasing hormone (CRH) mediates stress responses in the brain-gut axis. Administration of CRH modulates brain activation, for example by controlling the autonomic nervous system in response to colorectal distention. Here, we investigated the relationship between sympathoadrenal and hypothalamic-pituitary-adrenal (HPA) responses to colorectal distention in patients with irritable bowel syndrome (IBS). We enrolled 32 patients with IBS (16 women and 16 men) and 32 healthy subjects (16 women and 16 men), and randomly divided them between CRH and saline injection groups. The patients randomly underwent no (0 mmHg), mild (20 mmHg), or strong (40 mmHg) colorectal distension. CRH (2 μg/kg) or saline was then administered via injection, and the distention protocol was repeated. The heart rate (HR) and HR variability (HRV; calculated as the low [LF] to high frequency [HF] peak ratio, LF/HF) were analyzed using electrocardiography. Plasma noradrenaline, adrenaline, adrenocorticotropic hormone (ACTH), and cortisol levels were measured at the time of each distention. Plasma adrenaline levels were shown to be associated with plasma ACTH levels in HCs injected with CRH during distention using structural equation modeling analysis. Patients with IBS injected with placebo during distention displayed a closer association between these two parameters than those injected with CRH. Generalized estimating equation analysis revealed a significant distention × group × drug interaction for HF power. Moreover, there was a strong correlation between adrenaline and HRV upon CRH injection in controls, but not patients with IBS. The relationship between HPA-sympathoadrenal responses and CRH levels during colorectal distention differs between patients with IBS and controls. Modulation of adrenal gland activity in response to ACTH stimulation may contribute to the brain-gut pathophysiology characteristic of IBS.</p></div

Features of HRV during each distention and correlation between HRV and neuroendocrine variables.

<p>Features of HRV during each distention and correlation between HRV and neuroendocrine variables.</p

Effects of CRH on HRV during random distention after injection.

<p>(<b>A</b>) HR (beats/min), (<b>B</b>) HF power, and (<b>C</b>) LF/HF ratio in HCs administered with saline (n = 16) or CRH (n = 16); and patients with IBS administered with saline (n = 16) or CRH (n = 16). Results are represented as mean ± SD. GEE analysis of HRV parameters during random distention revealed a significant distention × group × drug interaction for HF power (<i>P</i> = .016). LF, low frequency; HF, high frequency; HCs, healthy controls.</p

Neuroendocrine response models during 40 mmHg distention.

<p>(<b>A</b>) HCs injected with saline (n = 16), (<b>B</b>) HCs injected with CRH (n = 16), (<b>C</b>) patients with IBS injected with saline (n = 16), and (<b>D</b>) patients with IBS injected with CRH (n = 16). *<i>P</i> < .0125 indicate significant paths. The squared multiple correlations (R²) of the variables are reported in the top right corner. There were no significant factor correlations between ACTH and NA. ACTH, plasma ACTH; cortisol, serum cortisol; HCs, healthy controls; NA, plasma noradrenaline; Ad, plasma adrenaline; ACTH, adrenocorticotropic hormone; IBS, irritable bowel syndrome; CRH, corticotropin-releasing hormone.</p

Effects of CRH on HRV during the baseline period after injection.

<p>(<b>A</b>) HR (beats/min), (<b>B</b>) HF power, and (<b>C</b>) LF/HF ratio in HCs administered with saline (n = 16) or CRH (n = 16); and patients with IBS administered with saline (n = 16) or CRH (n = 16). Results are represented as mean ± SD. *<i>P</i> < .05 when compared with placebo; baseline after CRH or saline injection, paired t-test. LF, low frequency; HF, high frequency; HCs, healthy controls.</p

Additional file 2: Figure S2. of Abdominal bloating is the most bothersome symptom in irritable bowel syndrome with constipation (IBS-C): a large population-based Internet survey in Japan

Online questionnaire for the main study (written in Japanese). (PDF 1000 kb

IBS subtype and CRH-BP SNP.

<p>We analyzed the associations between the SNPs and psychometric scores according to IBS subtype. (a) In individuals with diarrhea-type IBS, <i>rs10474485</i> A allele non-carriers showed higher scores than carriers. There were significant differences in the PSS (p = 0.018) and Trait (p = 0.017) scores. (b) In addition, in the IBS group with mixed symptoms, a significant difference was observed in the SDS score (p = 0.030). There was no significant difference in the constipation group. *p <i><</i> 0.05.</p

Irritable Bowel Syndrome Is Positively Related to Metabolic Syndrome: A Population-Based Cross-Sectional Study

<div><p>Irritable bowel syndrome is a common gastrointestinal disorder that may affect dietary pattern, food digestion, and nutrient absorption. The nutrition-related factors are closely related to metabolic syndrome, implying that irritable bowel syndrome may be a potential risk factor for metabolic syndrome. However, few epidemiological studies are available which are related to this potential link. The purpose of this study is to determine whether irritable bowel syndrome is related to metabolic syndrome among middle-aged people. We designed a cross-sectional study of 1,096 subjects to evaluate the relationship between irritable bowel syndrome and metabolic syndrome and its components. Diagnosis of irritable bowel syndrome was based on the Japanese version of the Rome III Questionnaire. Metabolic syndrome was defined according to the criteria of the American Heart Association scientific statements of 2009. Dietary consumption was assessed via a validated food frequency questionnaire. Principal-components analysis was used to derive 3 major dietary patterns: “Japanese”, “sweets-fruits”, and “Izakaya (Japanese Pub) “from 39 food groups. The prevalence of irritable bowel syndrome and metabolic syndrome were 19.4% and 14.6%, respectively. No significant relationship was found between the dietary pattern factor score tertiles and irritable bowel syndrome. After adjustment for potential confounders (including dietary pattern), the odds ratio (95% confidence interval) of having metabolic syndrome and elevated triglycerides for subjects with irritable bowel syndrome as compared with non-irritable bowel syndrome are 2.01(1.13–3.55) and 1.50(1.03–2.18), respectively. Irritable bowel syndrome is significantly related to metabolic syndrome and it components. This study is the first to show that irritable bowel syndrome was significantly related to a higher prevalence of metabolic syndrome and elevated triglycerides among an adult population. The findings suggest that the treatment of irritable bowel syndrome may be a potentially beneficial factor for the prevention of metabolic syndrome. Further study is needed to clarify this association.</p></div

Study flow.

<p>We conducted a cross-sectional study of 1,686 university students. Statistical analysis was performed using the data collected from 1,663 participants. Of these 1,663 participants, 341 (21%) were diagnosed with IBS.</p

Relationships between Subtypes of IBS Status and Odds Ratios (ORs) for Experiencing Employment Anxiety in Academic Life.

<p>D-IBS: IBS with diarrhea; C-IBS: IBS with constipation; M-IBS: Mixed IBS; U-IBS: unsubtyped IBS</p><p>Relationships between Subtypes of IBS Status and Odds Ratios (ORs) for Experiencing Employment Anxiety in Academic Life.</p