Increased gut permeability in first-degree relatives of children with irritable bowel syndrome or functional abdominal pain

Authors: MCOMBER, MARK - Phoenix Children'S Hospital; RAFATI, DANNY - Cook Children'S Hospital; CAIN, KEVIN - University Of Washington; DEVARAJ, SRIDEVI - Baylor College Of Medicine; WEIDLER, ERICA - Children'S Nutrition Research Center (CNRC); HEITKEMPER, MARGARET - University Of Washington; SHULMAN, ROBERT - Children'S Nutrition Research Center (CNRC)

Submitted to: Clinical Gastroenterology and Hepatology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/14/2019
Publication Date: 2/1/2020
Citation: McOmber, M., Rafati, D., Cain, K., Devaraj, S., Weidler, E.M., Heitkemper, M., Shulman, R.J. 2020. Increased gut permeability in first-degree relatives of children with irritable bowel syndrome or functional abdominal pain. Clinical Gastroenterology and Hepatology. 18(2):375-384. https://doi.org/10.1016/j.cgh.2019.05.011
DOI: https://doi.org/10.1016/j.cgh.2019.05.011

Interpretive Summary: The strength of the lining of the gastrointestinal (GI) tract plays a critical role in protecting the body from things in the diet that can cause illness. The strength of the lining of the GI tract can be measured easily in children and adults. It is known that many people with irritable bowel syndrome (IBS), a very common disorder, have a weak intestinal lining which increases the risk of IBS symptoms. In this study we discovered that this weak GI tract lining also is present in the siblings and parents of children who have IBS. Future studies will determine if this weakness is due to genetic or an environmental influences, potentially the diet. The results will help us find treatments to improve the strength of the lining of the GI tract and thereby reduce IBS symptoms.

Technical Abstract: Increased gut permeability might contribute to the pathogenesis of irritable bowel syndrome or functional abdominal pain (IBS or FAP). We investigated whether siblings and parents of children with IBS or FAP have increased gut permeability. We performed permeability tests (using sucrose, lactulose, mannitol, and sucralose) on 29 siblings and 43 parents of children with IBS or FAP, and 43 children (controls) and 42 parents of controls, from primary and secondary care. Permeability studies were repeated in 7 siblings and 37 parents of children with IBS or FAP and 23 controls and 36 parents of controls following ingestion of 400 mg of ibuprofen. Percent recovery of sucrose was calculated based on analyses of urine collected overnight; the lactulose/mannitol ratio and percent recovery of sucralose were based on analyses of urine samples collected over a 24-hour period. When we controlled for age, sex, and family membership, siblings of children with IBS or FAP had increased small bowel permeability (urinary lactulose/mannitol ratio) vs controls (P = .004). There was no difference in gastroduodenal (percent sucrose recovery) or colonic (percent sucralose recovery) permeability between groups. Similarly, parents of children with IBS or FAP also had increased small bowel permeability, compared with parents of controls (P = .015), with no differences in gastric or colonic permeability. After administration of ibuprofen, gastroduodenal and small bowel permeability tended to be greater in IBS or FAP siblings (P = .08) and gastroduodenal permeability tended to be greater in IBS or FAP parents (P = .086). Siblings and parents of children with IBS or FAP have increased baseline small intestinal permeability compared with control children and their parents. These results indicate that there are familial influences on gastrointestinal permeability in patients with IBS or FAP.