Location: Children's Nutrition Research CenterTitle: Activation of the innate immune system in children with irritable bowel syndrome evidenced by increased fecal human B-defensin-2
|SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)|
|DEVARAJ, SRIDEVI - Texas Children'S Hospital|
|HEITKEMPER, MARGARET - University Of Washington|
Submitted to: Clinical Gastroenterology and Hepatology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2020
Publication Date: 9/20/2020
Citation: Shulman, R.J., Devaraj, S., Heitkemper, M. 2020. Activation of the innate immune system in children with irritable bowel syndrome evidenced by increased fecal human B-defensin-2. Clinical Gastroenterology and Hepatology. https://doi.org/10.1016/j.cgh.2020.09.034.
Interpretive Summary: Ten to 15% of children worldwide suffer from irritable bowel syndrome (IBS). The cause of IBS is unknown. However, in this study we discovered that a portion of children with IBS have evidence that the immune system in the intestines is activated and more active than in healthy children. The activation of the immune system correlated with how bad the belly pain was. This will help us determine what things might be done to treat the immune activation and thereby reduce belly pain in these children.
Technical Abstract: The role of the innate immune system in functional gastrointestinal pain disorders is unclear. We investigated the role of B-defensin-2 and gut permeability in childhood irritable bowel syndrome (IBS) and functional abdominal pain (FAP) symptom generation. Fecal B-defensin-2 (and in a subset, gut permeability) was measured in children with IBS (n=116), FAP (n=33), and healthy control (HC) children (n=72). IBS and FAP patients were recruited from tertiary and primary care, and HCs were recruited from primary care. B-defensin-2 concentration was greater in children with IBS (P=.003) and FAP (P=.03) than in HCs. B-defensin-2 was greater in girls with IBS than female HCs (P=.007) and in girls with IBS vs boys with IBS (P=.036). There was no difference by sex in the FAP and HC groups. For the entire cohort, B-defensin-2 correlated with multiple pain symptoms. In the IBS group, B-defensin-2 correlated with pain interference (P=.014). No correlation with pain was found in the FAP or HC group. Gut permeability was greater in the IBS vs the FAP and HC groups(P=.038). For the entire cohort, permeability correlated with the number of pain episodes(P=.041) and interfering pain episodes (P=.049). For the entire cohort there was a correlation between B-defensin-2 and permeability (P=.003), with borderline correlation in the IBS group (P=.086). For the cohort and IBS and HC groups, the number of bowel movements was modestly inversely related to fecal B-defensin-2 concentrations. Increased fecal B-defensin-2 concentration in children with IBS suggests activation of the innate immune system in some, which, along with increased gut permeability, appears related to abdominal pain symptoms. Sex is an important variable in interpreting B-defensin-2 concentration in children with IBS.