Su1368 Undernutrition and Altered Gut Secretory IgA Synergistically Increase Bacterial Burdens in the Mesenteric Lymph Nodes

Background Cystic fibrosis (CF) is a life-limiting disease. Microbial infections, colonization and airway inflammation are the hallmarks of CF lung disease. Similarly, small bowel bacterial overgrowth has been long recognized as a complication of CF. With the recent availability of non-culture-based microbiological techniques, the presence of intestinal dysbiosis in CF has been confirmed. Defects in bacterial host defenses in the CF airways have been speculated and extensively investigated. However, the role of the innate immune system in the intestines of patients with CF remain poorly studied. Human β-defensin 2 (HBD-2) is an antimicrobial protein produced by epithelial surfaces, and upregulated by inflammation. Its expression in the CF intestine is unknown. Methods Faeces from children (aged 0-18 years) with CF and age-matched healthy controls (HC) were collected for faecal HBD-2 and calprotectin. Patients with CF with a pulmonary exacerbation requiring intravenous antibiotics were excluded. Any CF and HC subjects with gastroenteritis, on oral corticosteroids, probiotics and/or non-steroidal anti-inflammatory drugs in the preceding two weeks were also excluded. Results Thirty-three CF patients with mean (SD) age of 7.3 (3.8) years were recruited. Nineteen subjects (58%) were males. Twenty-nine (88%) were PI and 4 (12%) were PS. As a comparison, 33 age-matched HC were enrolled; 14 (42%) were males. There were no significant differences between CF and HC subjects for age (mean (SD) of 7.3 (3.8) vs. 7.0 (4.6) years respectively; P = 0.78) and gender (P = 0.33). All CF patients had detectable faecal HBD-2. There were no difference between faecal HBD-2 in CF and HC (median (IQR): 49.1 (19.7-77.2) vs. 43.4 (26.5-71.9)ng/g; P=0.7), and between PI and PS CF subjects (median (IQR): 49.1 (19.3 77.2) and 46.9 (32.0 104.4) ng/g; P = 0.6). CF subjects with faecal calprotectin ≥50mg/kg and <50mg/kg were also not different (50.5 (19.6-80.2) vs. 43.0 (19.0-70.4); P=0.7). There was no correlation between faecal HBD-2 and calprotectin in CF (r = 0.14; P = 0.4). Conclusions Faecal HBD-2 levels were not increased in children with CF, in inflamed or non-inflamed states. The lack of HBD-2 induction and upregulation under inflammatory conditions may suggest a diminished intestinal innate immune response in CF.