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Probiotics Effectively Treat Irritable Bowel Syndrome in Children
Abstract & Commentary
By Donald Brown, ND. Dr. Brown is Managing Director, Natural Products Research Consultants, Seattle, WA; he reports that he is a retained consultant at Schwabe North America (Nature's Way, Enzymatic Therapy).
Synopsis: Results of this 8-week clinical trial demonstrated the efficacy of Lactobacillus rhamnosus strain GG (LGG) in reducing the frequency and severity of pain in children with irritable bowel syndrome or functional abdominal pain. Benefits persisted for 8 weeks after cessation of treatment. Additionally, small intestinal permeability was decreased in children with IBS treated with LGG.
Source: Francavilla R, et al. A randomized controlled trial of Lactobacillus GG in children with functional abdominal pain. Pediatrics 2010;126:e1445-e1452.
Recurrent abdominal pain (RAP) is estimated to affect 10%–15% of school-aged children.1 The pediatric Rome criteria have proposed four categories for RAP: irritable bowel syndrome (IBS), functional dyspepsia (FD), childhood functional abdominal pain (FAP), and abdominal migraine.2 Based on some published clinical trials indicating success using probiotics to treat IBS in adults as well as limited data in children,3 the researchers of this randomized, double-blind, placebo-controlled trial sought to determine whether probiotic therapy could reduce the frequency and severity of pain in children with a diagnosis of either IBS or FAP. Children (5 to 14 years of age) with a diagnosis of IBS or FAP, according to the Rome II diagnostic criteria, were enrolled in the study. Exclusion criteria included chronic diseases, antibiotic or probiotic therapy within the previous 2 months, and pain history suggestive of functional dyspepsia/aerophagia/abdominal migraine.
The 20-week study was divided into three parts: 1) a 4-week run-in phase (weeks 1-4); 2) an 8-week treatment period (weeks 5-12); and 3) an 8-week follow-up phase (weeks 13-20). During the treatment period, children were randomly assigned to receive oral capsules containing either Lactobacillus rhamnosus strain GG (LGG; 3 x 109 colony forming units) or oral placebo twice per day. Throughout the 20-week study, children recorded the frequency and severity of pain using a combination of a self-reported visual analog scale and the Faces Pain Scale. Parental assessment of overall of pain relief was obtained by interviewing them just before and after the treatment period. Additionally, intestinal permeability was tested using the lactulose-to-mannitol ratio (La/Ma) test. The test was performed one day before and after the 8-week treatment period. Fifty-five children with no history of RAP were recruited to assess the normal range of La/Ma and were used as a control group. The primary outcome was the change in abdominal pain (frequency and severity) from baseline to the end of the treatment period. Secondary outcomes included at least a 50% decrease in the number of episodes and intensity of pain (treatment success), a decrease in perception of children's pain according to parents, and modification of intestinal permeability.
a.total of 141 children underwent randomization and 136 children completed the study (n = 67 in the LGG group). Of the children completing the study, 80 were diagnosed with IBS (n = 42 in the LGG group) and 56 with FAP (n = 25 in the LGG group). In the children with IBS, the number of episodes of pain per week during the 4-week run-in was 3.4 ± 2.3 in the LGG group and 4.0 ± 3.5 in the placebo group. The number of painful episodes at the end of the 8-week treatment period (week 12) were 1.6 ± 0.8 and 3.2 ± 1.9, respectively (P < 0.001). At the end of the 8-week follow-up period (week 20), the number of episodes of pain per week were 0.9 ± 0.2 for the LGG group compared to 1.6 ± 0.9 for the placebo group (P < 0.001). The severity of pain at baseline was 4.4 ± 2.1 for the LGG group and 4.6 ± 2.8 for the placebo group. After the treatment period, severity of pain was 2.5 ± 1.2 and 3.6 ± 2.2, respectively (P < 0.001). At week 20, severity of pain was 1.8 ± 0.3 in the LGG group compared to 3.3 ± 1.5 in the placebo group (P < 0.001). At week 12, treatment success was achieved in 82% of the children in the LGG group compared to 45% in the placebo group (P < 0.01). Treatment success at 20 weeks was 87% and 50%, respectively (P < 0.01). Children with a diagnosis of FAP did not show significant changes in either number of episodes or severity of pain compared to placebo. The only exception was a small improvement in pain intensity at week 20 compared to placebo. According to the researchers, LGG was well tolerated and there were no adverse effects reported.
Only 54 children participated in the intestinal permeability test (IPT). Compared with control subjects, 32 of 54 children had abnormal IPT (mean La/MA: 0.035) irrespective of whether they were diagnosed with IBS or FAP. At week 12, there was a significant reduction in intestinal permeability in children with IBS taking LGG compared to placebo (P < 0.02) but not in those with FAP. There was no correlation between the IPT and severity of symptoms.
IBS is the most common functional gastrointestinal disorder with a reported prevalence in the general population between 12%-22%.4 Children with IBS represent 25%-50% of all patients presenting to pediatric gastroenterology clinics.5 However, beside reassurance and counseling on managing pain, conventional therapies have shown inconclusive results in the treatment of RAP, including IBS.6
a.2009 meta-analysis reported on the findings of 14 placebo-controlled trials using probiotics for the treatment of IBS.3 Although the majority of studies were with an adult population, two pediatric trials reported on the use of the probiotic strain LGG for the treatment of FAP and IBS.7,8 Despite methodological limitations in both trials (e.g., small sample size and short treatment duration), one study found minimal efficacy (slight improvement in abdominal distension) in children with IBS7 while the other reported efficacy in children with IBS, but not FAP and FD.8 Interestingly, in both adult and pediatric trials demonstrating efficacy for IBS, the predominant symptom alleviated by probiotics was abdominal pain.3
The reviewed clinical trial improves on the design of the previous positive trial with LGG. While using the same daily dose of LGG, the study not only includes a longer treatment period (8 weeks vs. 4 weeks) but also an 8-week follow-up phase. It is interesting to note that the findings of this trial mirror those of the earlier trial. Specifically, that LGG appears to provide symptoms relief for children with IBS but not FAP. As opposed to the earlier trial, the current study demonstrated a significant decrease in both the severity and frequency of pain. Of particular interest is the finding that those subjects with IBS taking LGG continued to have significant symptom relief for 8 weeks after the cessation of treatment. Also notable was the absence of adverse events in those taking LGG.
a.though only measured in a handful of children, the intestinal permeability findings are also notable in this study. Abnormal intestinal permeability has been found in adults with diarrhea predominant IBS.9 Probiotics have been shown to decrease intestinal permeability in preterm infants10 as well as healthy Egyptian children.11 The current study clearly demonstrates a decrease in permeability in children with IBS taking LGG. While altered intestinal permeability still has not been established firmly as a cause or effect of IBS, there is growing evidence that it may play a role in both pediatric FAP and IBS.12 There is also growing evidence that patients with IBS are likely to demonstrate dysbiosis (small intestinal bacterial overgrowth)13 to argue in favor of probiotic therapy for the condition.
It should be noted that the reporting of the results of this study are confusing and bring into question the editorial rigor of the journal. There are inconsistencies between the reported numbers of children in each group included in the intention-to-treat analysis in a figure showing enrollment, assignment, intervention, and follow-up and the tables reporting the primary and secondary outcomes. Also, the outcomes reported in the Results section of the paper appear to combine both diagnoses. A closer look at the specific results by diagnosis shown in Tables 2 and 3 basically demonstrate an excellent treatment response for children with IBS and essentially none for those with FAP. The results reported in my summary of the study reflect that data as reported by specific diagnosis.
Taking off an editorial hat and replacing it with a clinical one, the reality is that while pediatric gastroenterologists may have the tools and expertise to differentiate between IBS and FAP, the division between specific diagnoses is not always clear in pediatric practice. While IBS is often a more clear-cut diagnosis in adults, children present a more complicated challenge due to the often non-specific nature of their chronic abdominal pain that encompasses a heterogeneous group of patients. The researchers chose to include children with FAP because the condition has been found to be a precursor of IBS in adults.
So, while this study certainly lays the groundwork for a follow-up trial using LGG specifically in children with IBS, it provides us with a promising and safe therapeutic option for a condition currently lacking in efficacious treatment options. In short, a therapeutic trial with LGG may be indicated in any child meeting any of the pediatric Rome criteria for RAP.
1. Saps M, et al. A prospective school-based study of abdominal pain and other common somatic complaints in children. J Pediatr 2009;154;322-326.
2. Rasquin A, et al. Childhood functional gastrointestinal disorders:child/adolescent. Gastroenterology 2006;130:1527-1537.
3. Hoveyda N, et al. A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol 2009;9:15(doi:10.1.1186/1471-230X-9-15).
4. Mertz HR. Iritable bowel syndrome. N Engl J Med 2003;349:2136-2146.
5. Everheart JE, et al. Irritable bowel syndrome in office-based practice in the United States. Gastroenterol 1991;100:998-1005.
6. Weydert JA, et al. Systematic review of treatments for recurrent abdominal pain. Pediatrics 2003;111:e1-11.
7. Baussermann M, et al. The use of Lactobacillus GG in irritable bowel syndrome in children: A double-blind randomized control trial. J Pediatr 2005;147:197-201.
8. Gawronska A, et al. A randomized double-blind placebo-controlled trial of Lactobacillus GG for abdominal pain disorders in children. Aliment Pharmacol Ther 2007;25:177-184.
9. Dunlop SP, et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006;101:1288-1294.
10. Stratiki Z, et al. The effect of bifidobacter supplemented bovine milk on intestinal permeability of preterm infants. Early Human Dev 2007;83:575-579.
11. Mohammad M, et al. The impact of probiotic and/or honey supplements on gut permeability among Egyptian children. J Nutr Environmental Med 2007;16:10-15.
12. Shulman RJ, et al. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr 2008;153:646-650.
13. Lin HC. Small intestinal bacterial overgrowth: A framework for understanding irritable bowel syndrome. JAMA 2004;292:852-858.