Original article
Alimentary tract
Increased Gut Permeability in First-degree Relatives of Children with Irritable Bowel Syndrome or Functional Abdominal Pain

https://doi.org/10.1016/j.cgh.2019.05.011Get rights and content

Background & Aims

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.

Methods

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.

Results

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).

Conclusions

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.

Section snippets

Subjects

Both sibling and parent groups (IBS and FAP, control) were recruited by contacting families who had participated in our previous observational studies that recruited both IBS and FAP children and age- and sex-matched controls.14, 15, 16, 17 One of these studies examined gut permeability in children with IBS and FAP in comparison with healthy children.14 We estimated a sample size of 15–21 children and 26–33 adults would be needed to detect a statistically significant difference between groups

Subjects

A total of 43 families with a child who had IBS or FAP and 42 families with control children completed the baseline study (Table 1). There were no differences in age or sex between the IBS or FAP and control children or between IBS or FAP and control adults (Table 1). Body mass index was similar between groups, with the exception it was greater in male IBS and FAP siblings than in male control siblings (Table 1).

Seven siblings and 37 parents of children with IBS or FAP were willing to repeat

Discussion

Our study evaluates GI permeability in first-degree relatives of children with IBS or FAP. Our results show that siblings and parents of children with IBS or FAP have increased baseline lactulose/mannitol ratio compared with siblings of control children and their parents (Table 3). Baseline sucrose and sucralose permeability did not differ between groups.

It might be assumed that the increased permeability in the IBS or FAP families might be associated with GI symptoms. However, like IBD, IBS

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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported in part by R01 NR05337 from the National Institutes of Health, the Daffy’s Foundation, the USDA/ARS under Cooperative Agreement No. 6250-51000-043, and P30 DK56338, which funds the Texas Medical Center Digestive Disease Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work is a publication of the USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital. The contents do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.

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