Subacute stress and chronic stress interact to decrease intestinal barrier function in rats.

Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon.

Gastroesophageal reflux disease is inversely related with glycemic control in morbidly obese patients.

BACKGROUND: The link between diabetes mellitus and gastroesophageal reflux disease (GERD) is controversial. We assessed the relationship between glycemic control (GC) and GERD in morbidly obese patients. METHODS: Consecutive patients with morbid obesity (n = 86) underwent manometry, pH-metry, endoscopy, and contrasted X-ray after responding to a GERD questionnaire and dosing fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients with poor GC (HbA1c, 6.1-10% and FPG < 140 mg/dl) and those with very poor GC (HbA1c > 10% or FPG > 140 mg/dl) were compared. RESULTS: There were 63 patients with poor GC and 17 with very poor GC. Compared to patients with very poor GC, patients with poor GC showed higher heartburn scores [8 (0-12) vs. 0 (0-4); P = 0.003]; higher total esophageal acid exposure [5.2% (2.5-10.5%) vs. 2.3% (0.8-7.5%); P = 0.041]; lower distal esophageal amplitude (105 ± 38 vs. 134 ± 63 mmHg; P = 0.019); higher expiratory gastroesophageal pressure gradient (GEPG, 7 ± 3.4 vs. 5.2 ± 3 mmHg; P = 0.050); lower ventilatory gradient (inspiratory-expiratory GEPG, 10.9 ± 3.8 vs. 13.6 ± 4.1 mmHg; P = 0.012); lower waist-to-hip ratio (0.95 vs. 1; P = 0.040); and more hiatal hernia (38% vs. 6%; P = 0.016). CONCLUSIONS: This study suggests an inverse relation between glycemic control and GERD in morbidly obese patients. This can be partially explained by a lower frequency of hiatal hernia in patients with very poor glycemic control.