Our data suggest that children with FAP/IBS have increased permeability in the proximal GI tract and colon. These data are in contrast to adults with IBS where increased small intestinal permeability (i.e., increased lactulose/mannitol ratio) has been found although site specific testing has not been done throughout the GI tract (26
Only a few studies have measured intestinal permeability in children with recurrent abdominal pain and these studies were for the most part prior to the recommendation that recurrent abdominal pain be differentiated into FAP/IBS. Amery and Forget used 51
Cr-EDTA which measures permeability throughout the GI tract (i.e., not site specific) (28
). These investigators found increased permeability but only in children with documented duodenitis (i.e., they did not meet criteria for FAP/IBS) (28
). Barau and Dupont carried out permeability testing in a small number of children (n = 17; 2–14 years of age) with IBS as defined by recurrent abdominal pain or chronic diarrhea > 3 months; a definition that does not meet criteria for IBS (31
). Their findings suggested that the increased lactulose/mannitol in some children may be related to food allergy (31
). However, the one child in the FAP/IBS group and the one child in the Control group who reported food allergies were already on an exclusion diet.
One study in adults with IBS measured colonic permeability by timing the collection of the 51
). Using this technique no increase in permeability was noted (10
). Whether the increased colonic permeability noted in the children with FAP/IBS reflects the low grade inflammation found in some adults with IBS requires further study (32
Our results suggest that children with FAP/IBS also have increased fecal calprotectin. GI inflammation can increase fecal calprotectin concentration, a calcium binding protein found in neutrophils, monocytes, and macrophages that resists degradation in the GI tract and is excreted in feces (33
). Up to one third of adult patients with IBS also have increased fecal calprotectin concentration (9
In contrast, the few previous data in children with recurrent abdominal pain suggested that fecal calprotectin concentration was not increased compared with controls (11
). However, a study by Olafsdottir et al demonstrated a significant decline in fecal calprotectin concentration in children with age and the mean age of the Control children (5.3 years of age; n = 23) was much less than the children with recurrent abdominal pain (11.9 years of age; n = 19) (11
). These two factors (decline of fecal calprotectin concentration with age and older age of the recurrent abdominal pain children) and the smaller sample size compared with our study may have obscured potential differences between groups (11
). Berni Canani et al measured fecal calprotectin concentration in children with functional disorders (n = 44) and Controls (n = 76) (12
). There were no differences between the groups in fecal calprotectin concentrations. However, the functional disorders were not defined further (e.g., FAP/IBS, dyspepsia, colic) and the age ranges were wide (Controls: 1 – 18 years, Functional disorders: 1 – 13 years) (12
). Thus, it is difficult to compare their results with ours.
We anticipated there would be a relationship between mucosal abnormalities as defined by increased GI permeability and fecal calprotectin concentration and pain symptoms and stool characteristics. To our surprise, only fecal calprotectin concentration was related to pain symptoms, and in that case, only to how much the pain interfered with activity. These data suggest that the relationship between GI permeability, mucosal inflammation, and pain symptoms is more complex than initially thought. Indeed, our data fit with the observation in adults with constipation-predominant or postinfectious IBS that there is no correlation between GI permeability and GI symptoms (10
). Data from neonatal stress models suggest that a stress engendered shortly after birth can manifest as increased GI permeability in the neonatal period and into adulthood (34
). These animal data fit with clinical observations that humans stressed as infants are more likely to develop functional bowel symptoms (35
). Thus, we speculate that increased permeability in our children may be present from a young age perhaps explaining, in part, the disconnect between increased permeability and pain and stooling symptoms in our children 7
years of age.
Fecal calprotectin concentration did correlate with the degree to which pain interfered with the children’s activities. Similar to our findings in children, in adults there also appeared to be no correlation between GI permeability and fecal calprotectin concentration (10
). It may be that different mechanisms are operative in engendering an increase in GI permeability vs. fecal calprotectin concentration in children with FAP/IBS or adults with IBS.
There are some limitations to our study. Although all children with FAP/IBS were thoroughly screened and had some diagnostic testing, it is possible that some children may have had other conditions. However, given that the children had to have had at least three months of pain prior to admission into the study and had been evaluated by their pediatrician and in some cases by a pediatric gastroenterologist prior to recruitment, the actual time from onset of symptoms to follow up was much greater than our mean of 12.3 months. Thus, it is unlikely that a significant organic disorder would have been missed. Also, despite the relatively large sample size, it is possible that a larger study may have uncovered further correlations among the variables studied.
In summary, we have shown that children with FAP/IBS have evidence of increased proximal GI and colonic permeability and have GI inflammation as reflected by fecal calprotectin concentration. We also have demonstrated that fecal calprotectin concentration bears some relationship with the degree to which pain limits activities.