Probiotics for stomach pain in children
Probiotics may be better than placebo (dummy treatment) at improving stomach pain for children with functional abdominal pain.
Synbiotics may be better than placebo (dummy treatment) at improving stomach pain for children with functional abdominal pain.
What is functional abdominal pain?
Functional abdominal pain is a common problem in children. The term functional abdominal pain is used when no cause can be found for the symptoms. These symptoms include frequent stomach pain that has lasted for at least six months, which causes problems in daily life.
What are probiotics?
Probiotics are live bacteria and yeasts, promoted as having various health benefits. They are often referred to as 'good bacteria'. It is thought that these probiotics may help the natural balance of bacteria in the gut and may improve symptoms in certain illnesses. They can also be added to agents called prebiotics (foods that support the growth of these bacteria and yeasts) and when these are put together in a single preparation, this is a called a synbiotic.
What did we want to find out?
We wanted to find out if probiotics and synbiotics can be used for the treatment of functional abdominal pain in children and whether they are safe to use.
What did we do?
We searched for studies that looked at probiotics or synbiotics compared with placebo, no treatment or another intervention in children aged between 4 and 18 years with a diagnosis of functional abdominal pain disorder. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 18 studies with a total of 1309 children, which compared probiotics or synbiotics with placebo.
We found that probiotics may provide better pain relief and relief from other stomach problems than placebo for children with functional abdominal pain. In particular, in children taking probiotics, treatment was judged a success more often than in those taking a placebo. Synbiotics also showed a difference from placebo but this was based on a smaller number of studies. There was not enough information to consider changes in the frequency of pain when comparing synbiotics to placebo.
We cannot reach any conclusions about safety as the evidence we found on any unwanted or harmful effects was of very low certainty.
What are the limitations of the evidence?
The evidence for synbiotics in this review is limited by the fact that the results are from fewer studies. In terms of safety, there were not enough cases of unwanted or harmful effects to give a clear picture about the safety of probiotics and synbiotics.
How up to date is this evidence?
This evidence is up to date to October 2021.
The results from this review demonstrate that probiotics and synbiotics may be more efficacious than placebo in achieving treatment success, but the evidence is of low certainty. The evidence demonstrates little to no difference between probiotics or synbiotics and placebo in complete resolution of pain. We were unable to draw meaningful conclusions about the impact of probiotics or synbiotics on the frequency and severity of pain as the evidence was all of very low certainty due to significant unexplained heterogeneity or imprecision.
There were no reported cases of serious adverse events when using probiotics or synbiotics amongst the included studies, although a review of RCTs may not be the best context to assess long-term safety. The available evidence on adverse effects was of very low certainty and no conclusions could be made in this review. Safety will always be a priority in paediatric populations when considering any treatment. Reporting of all adverse events, adverse events needing withdrawal, serious adverse events and, particularly, long-term safety outcomes are vital to meaningfully move forward the evidence base in this field.
Further targeted and appropriately designed RCTs are needed to address the gaps in the evidence base. In particular, appropriate powering of studies to confirm the safety of specific strains not yet investigated and studies to investigate long-term follow-up of patients are both warranted.
Functional abdominal pain is pain occurring in the abdomen that cannot be fully explained by another medical condition and is common in children. It has been hypothesised that the use of micro-organisms, such as probiotics and synbiotics (a mixture of probiotics and prebiotics), might change the composition of bacterial colonies in the bowel and reduce inflammation, as well as promote normal gut physiology and reduce functional symptoms.
To assess the efficacy and safety of probiotics in the treatment of functional abdominal pain disorders in children.
We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and two clinical trials registers from inception to October 2021.
Randomised controlled trials (RCTs) that compare probiotic preparations (including synbiotics) to placebo, no treatment or any other interventional preparation in patients aged between 4 and 18 years of age with a diagnosis of functional abdominal pain disorder according to the Rome II, Rome III or Rome IV criteria.
The primary outcomes were treatment success as defined by the primary studies, complete resolution of pain, improvement in the severity of pain and improvement in the frequency of pain. Secondary outcomes included serious adverse events, withdrawal due to adverse events, adverse events, school performance or change in school performance or attendance, social and psychological functioning or change in social and psychological functioning, and quality of life or change in quality life measured using any validated scoring tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). For continuous outcomes, we calculated the mean difference (MD) and corresponding 95% CI.
We included 18 RCTs assessing the effectiveness of probiotics and synbiotics in reducing the severity and frequency of pain, involving a total of 1309 patients.
Probiotics may achieve more treatment success when compared with placebo at the end of the treatment, with 50% success in the probiotic group versus 33% success in the placebo group (RR 1.57, 95% CI 1.05 to 2.36; 554 participants; 6 studies; I2 = 70%; low-certainty evidence).
It is not clear whether probiotics are more effective than placebo for complete resolution of pain, with 42% success in the probiotic group versus 27% success in the placebo group (RR 1.55, 95% CI 0.94 to 2.56; 460 participants; 6 studies; I2 = 70%; very low-certainty evidence). We judged the evidence to be of very low certainty due to high inconsistency and risk of bias.
We were unable to draw meaningful conclusions from our meta-analyses of the pain severity and pain frequency outcomes due to very high unexplained heterogeneity leading to very low-certainty evidence.
None of the included studies reported serious adverse events. Meta-analysis showed no difference in withdrawals due to adverse events between probiotics (1/275) and placebo (1/269) (RR 1.00, 95% CI 0.07 to 15.12). The results were identical for the total patients with any reported adverse event outcome. However, these results are of very low certainty due to imprecision from the very low numbers of events and risk of bias.
Synbiotics may result in more treatment success at study end when compared with placebo, with 47% success in the probiotic group versus 35% success in the placebo group (RR 1.34, 95% CI 1.03 to 1.74; 310 participants; 4 studies; I2 = 0%; low certainty). One study used Bifidobacterium coagulans/fructo-oligosaccharide, one used Bifidobacterium lactis/inulin, one used Lactobacillus rhamnosus GG/inulin and in one study this was not stated).
Synbiotics may result in little difference in complete resolution of pain at study end when compared with placebo, with 52% success in the probiotic group versus 32% success in the placebo group (RR 1.65, 95% CI 0.97 to 2.81; 131 participants; 2 studies; I2 = 18%; low-certainty evidence).
We were unable to draw meaningful conclusions from our meta-analyses of pain severity or frequency of pain due to very high unexplained heterogeneity leading to very low-certainty evidence.
None of the included studies reported serious adverse events. Meta-analysis showed little to no difference in withdrawals due to adverse events between synbiotics (8/155) and placebo (1/147) (RR 4.58, 95% CI 0.80 to 26.19), or in any reported adverse events (3/96 versus 1/93, RR 2.88, 95% CI 0.32 to 25.92). These results are of very low certainty due to imprecision from the very low numbers of events and risk of bias.
There were insufficient data to analyse by subgroups of specific functional abdominal pain syndrome (irritable bowel syndrome, functional dyspepsia, abdominal migraine, functional abdominal pain - not otherwise specified) or by specific strain of probiotic.
There was insufficient evidence on school performance or change in school performance/attendance, social and psychological functioning, or quality of life to draw conclusions about the effects of probiotics or synbiotics on these outcomes.