Review question
What are the benefits and risks of using probiotics to prevent Hirschsprung-associated enterocolitis (HAEC)?
Key messages
We compared randomised controlled trials (RCTS) of probiotics versus placebo, or any other non-probiotic intervention, to prevent Hirschsprung-associated enterocolitis (HAEC). There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of HAEC.
What is HAEC?
HAEC is a rare condition. It can cause inflammation of the bowels and lead to symptoms, such as abdominal pain and diarrhoea, which can disturb the balance of electrolytes in the body.
What are probiotics?
Probiotics are live bacteria that may restore the natural balance of bacteria, and possibly reduce inflammation of the gut. However, it is not yet clear whether taking probiotics is helpful in preventing HAEC, and if they are safe. We analysed the scientific evidence to answer this question.
What did we want to find out？
We wanted to find out if probiotics could prevent HAEC, and if probiotics were associated with any unwanted effects.
What did we do?
We searched for studies that examined probiotics compared with placebo or any other intervention in children with Hirschsprung's disease (HD). We compared and summarised the results of the studies, and rated our confidence in the evidence.
What did we find?
We included two RCTs, with a total of 122 people with HAEC. One multicentre trial was conducted in the USA and Egypt, and one in China. Each of these studies was carried out in a hospital setting. A total of 60 participants were treated with probiotics, and 60 were treated with a placebo (a fake medication). Time of enrolment ranged from 1 to 12 months. One study was funded by companies that supplied the probiotics; the other by government agencies. Taken together, the results suggest that there is not enough evidence to show that probiotics can prevent HAEC.
Main results
We are very uncertain whether there was a difference in the occurrence of HAEC between the group receiving probiotics and the group receiving placebo. No serious adverse events were reported. We are very uncertain about the effect of probiotics on the severity of HAEC.
No overall mortality or withdrawals due to adverse events were reported. There was little or no difference in the recurrence of HAEC between the two groups. Since the studies were very small, and poorly reported, we are unable to draw any definite conclusions at this time. Better-designed studies with more participants are needed.
What were the limitations of the evidence?
The certainty of the evidence varied from low to very low, mainly because the results were inconclusive, and there were not enough available date.
How up to date is this evidence?
The evidence is up to date to 27 February 2022.
There is currently not enough evidence to assess the efficacy or safety of probiotics for the prevention of Hirschsprung-associated enterocolitis when compared with placebo. The presence of low- to very-low certainty evidence suggests that further well-designed and sufficiently powered RCTs are needed to clarify the true efficacy of probiotics.
Hirschsprung-associated enterocolitis (HAEC) is a leading cause of serious morbidity and potential mortality in children with Hirschsprung's disease (HD). People with HAEC suffer from intestinal inflammation, and present with diarrhoea, explosive stools, and abdominal distension. Probiotics are live microorganisms with beneficial health effects, which can optimise gastrointestinal function and gut flora. However, the efficacy and safety of probiotic supplementation in the prevention of HAEC remains unclear.
To assess the effects of probiotic supplements used either alone or in combination with pharmacological interventions on the prevention of Hirschsprung-associated enterocolitis.
We searched CENTRAL, PubMed, Embase, the China BioMedical Literature database (CBM), the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov, the Chinese Clinical Trials Registry, Australian New Zealand Clinical Trials Registry, and Clinical Trials Registry-India, from database inception to 27 February 2022. We also searched the reference lists of relevant articles and reviews for any additional trails.
Randomised controlled trials (RCTs) comparing probiotics and placebo, or any other non-probiotic intervention, for the prevention of HAEC were eligible for inclusion.
Two review authors independently extracted data and assessed the risk of bias of the included studies; disagreements were resolved by discussion with a third review author. We assessed the certainty of evidence using the GRADE approach. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous outcomes.
We included two RCTs, with a total of 122 participants. We judged the overall risk of bias as high. We downgraded the evidence due to risk of bias (random sequence generation, allocation concealment, and blinding) and small sample size.
The evidence is very uncertain about the effect of probiotics on the occurrence of HAEC (OR 0.58, 95% CI 0.10 to 3.43; I² = 74%; 2 studies, 120 participants; very low-certainty evidence). We found one included study that did not measure serious adverse events and one included study that reported no serious adverse events related to probiotics. Probiotics may result in little to no difference between probiotics and placebo in relation to the severity of children with HAEC at Grade I (OR 0.66, 95% CI 0.14 to 3.16; I² = 25%; 2 studies, 120 participants; low-certainty evidence). The effects of probiotics on the severity of HAEC at Grade II are very uncertain (OR 1.14, 95% CI 0.01 to 136.58; I² = 86%; 2 studies, 120 participants; very low-certainty evidence). Similarly, the evidence suggests that probiotics results in little to no difference in relation to the severity of HAEC at Grade III (OR 0.43, 95% CI 0.05 to 3.45; I² = 0%; 2 studies, 120 participants; low-certainty evidence).
No overall mortality or withdrawals due to adverse events were reported. Probiotics may result in little to no difference in the recurrence of episodes of HAEC compared to placebo (OR 0.85, 95% CI 0.24 to 3.00; 1 study, 60 participants; low-certainty evidence).