P676 Influence of hypoxia on healthy volunteers and patients with inflammatory bowel disease
S. Vavricka*1, 2, P. Ruiz-Castro1, L. Biedermann1, M. Madanchi1, S. Scharl1, M. Scharl1, G. Rogler1, J. Zeitz1
1University Hospital Zurich, Department of Gastroenterology and Hepatology, Zurich, Switzerland, 2Triemli Hospital, Division of Gastroenterology and Hepatology, Zurich, Switzerland
Hypoxia can induce inflammation in the gastrointestinal tract, and a previous study from our group suggests an impact of hypoxia on the course of inflammatory bowel disease (IBD). We aimed to evaluate prospectively and under standardised conditions the effects that hypoxia has on healthy volunteers and on IBD patients.
In the study, 10 healthy volunteers, 11 Crohn’s disease (CD) patients, and 9 ulcerative colitis (UC) patients in stable remission underwent a 3-hour exposure to hypoxic conditions simulating an altitude of 4 000 metres above sea level in a hyperbaric pressure chamber situated at the Swiss Aeromedical Centres in Dubendorf, Switzerland. Stool samples analysing calprotectin and microbiota composition, biopsy samples from the rectosigmoid region and blood samples were repetitively collected and analysed in conjunction with detailed records of clinical symptoms.
In the healthy volunteer group (median age 24.8 years), no significant changes on the mRNA levels of p62 or IL-18 were revealed in biopsies taken from the sigmoid region on the day before the hypoxic chamber (T1), in biopsies taken directly after the hypoxic chamber (T2), or in biopsies taken 1 week after the chamber (T3). However, the calprotectin level showed a relevant increase in most volunteers up to 10 fold of the initial measured value. In CD patients (median age 35.6 years), mRNA levels of p62 and IL-18 increased significantly between T1 and T3 (for p62 4.144-fold increase, p < 0.05; for IL-18, 7.31-fold increase, p < 0.05). Further, calprotectin level increased up to 8 fold of the initial measured value. In UC patients (median age 31.1 years), mRNA levels of p62 and IL-18 increased between T1, T2, and T3 but did not reach statistical significance. Calprotectin levels increased up to 18-fold of the initial measured value. One patient in the UC group dropped out of the study because of a flare on T2. In addition, another 2 patients reported increased activity of their disease.
The importance of environmental factors in the pathogenesis, including their disease-modifying potential, are increasingly recognized in IBD. Understanding molecular and microbiological consequences of intestinal hypoxia may ultimately derive further insights on the pathogenesis of IBD, far beyond exposure to low partial oxygen pressure ambient air.