Abstract: We included 39 randomised controlled trials involving 2599 randomised participants. We included participants of either gender, aged from the first year of life through to 55 years (only six studies assessed adults), who had mild to severe eczema. Trials were undertaken in primary and secondary healthcare settings, mainly in Europe or Asia. Duration of treatment ranged from four weeks to six months, and duration of follow-up after end of treatment ranged from zero to 36 months. We selected no standard dose: researchers used a variety of doses and concentrations of probiotics. The probiotics used were bacteria of the Lactobacillus and Bifidobacteria species, which were taken alone or combined with other probiotics, and were given with or without prebiotics. Comparators were no treatment, placebo, and other treatments with no probiotics. For all results described in this abstract, the comparator was no probiotics. Active treatment ranged from six weeks to three months for all of the following results, apart from the investigator-rated eczema severity outcome, for which the upper limit of active treatment was 16 weeks. With regard to score, the higher the score, the more severe were the symptoms. All key results reported in this abstract were measured at the end of active treatment, except for adverse events, which were measured during the active treatment period. Probiotics probably make little or no difference in participant- or parent-rated symptoms of eczema (13 trials; 754 participants): symptom severity on a scale from 0 to 20 was 0.44 points lower after probiotic treatment (95% confidence interval (CI) -1.22 to 0.33; moderate-quality evidence). Trial sequential analysis shows that target sample sizes of 258 and 456, which are necessary to demonstrate a minimum mean difference of -2 and -1.5, respectively, with 90% power, have been exceeded, suggesting that further trials with similar probiotic strains for this outcome at the end of active treatment may be futile. We found no evidence suggesting that probiotics make a difference in QoL for patients with eczema (six studies; 552 participants; standardised mean difference (SMD) 0.03, 95% CI -0.36 to 0.42; low-quality evidence) when measured by the participant or the parent using validated disease-specific QoL instruments. Probiotics may slightly reduce investigator-rated eczema severity scores (24 trials; 1596 participants). On a scale of 0 to 103 for total Severity Scoring of Atopic Dermatitis (SCORAD), a score combining investigator-rated eczema severity score and participant scoring for eczema symptoms of itch and sleep loss was 3.91 points lower after probiotic treatment than after no probiotic treatment (95% CI -5.86 to -1.96; low-quality evidence). The minimum clinically important difference for SCORAD has been estimated to be 8.7 points. We noted significant to extreme levels of unexplainable heterogeneity between the results of individual studies. We judged most studies to be at unclear risk of bias; six studies had high attrition bias, and nine were at low risk of bias overall. We found no evidence to show that probiotics make a difference in the risk of adverse events during active treatment (risk ratio (RR) 1.54, 95% CI 0.90 to 2.63; seven trials; 402 participants; low-quality evidence). Studies in our review that reported adverse effects described gastrointestinal symptoms. Evidence suggests that, compared with no probiotic, currently available probiotic strains probably make little or no difference in improving patient-rated eczema symptoms. Probiotics may make little or no difference in QoL for people with eczema nor in investigator-rated eczema severity score (combined with participant scoring for eczema symptoms of itch and sleep loss); for the latter, the observed effect was small and of uncertain clinical significance. Therefore, use of probiotics for the treatment of eczema is currently not evidence-based. This update found no evidence of increased adverse effects with probiotic use during studies, but a separate adverse events search from the first review revealed that probiotic treatment carries a small risk of adverse events. Results show significant, unexplainable heterogeneity between individual trial results. Only a small number of studies measured some outcomes. Future studies should better measure QoL scores and adverse events, and should report on new probiotics. Researchers should also consider studying subgroups of patients (e.g. patients with atopy or food allergies, adults) and standardising doses/concentrations of probiotics given.

Plain-language summary: We included 39 randomised controlled clinical trials (RCTs) with 2599 participants, which we identified in searches up to January 2017. These studies included people of either gender and of all ages, although most studies assessed children who had been told by a healthcare professional that they had eczema. Participants had eczema ranging from mild to severe, and RCTs compared treatment with live micro-organisms (probiotics) of varying dose and concentration, taken by mouth, versus no treatment, placebo, or another treatment with no probiotics. The probiotics included were bacteria of the Lactobacillus and Bifidobacteria species taken alone or in combination with other probiotics for a period ranging from four weeks up to six months. We did not look at studies that were seeking to prevent eczema. Most studies were done in Europe, and some were done in Asia, Australia, and New Zealand - all in a medical setting. Most studies were conducted at a single centre. Reviewers applied no language restrictions on study selection. Ten studies were funded by companies supplying the probiotics, and another four studies did not declare the source of funding. Please note that results in this summary are based on the following: a comparison of probiotic against no probiotic; treatment over six weeks to three months, except for the investigator-rated eczema severity outcome, for which participants were treated longer (16 weeks); and outcomes measured at the end of the treatment period, apart from adverse events, which were assessed throughout treatment. Unless otherwise stated, outcomes were measured by participants or parents. The included studies assessed a variety of probiotics of differing concentrations or doses. With regard to score, the higher the score, the more severe were the symptoms. We found that currently available probiotics probably make little or no difference in reducing eczema symptoms, such as itching and sleep loss (moderate-quality evidence). However, we did find that these probiotics may slightly reduce the severity of eczema scored by patients and their healthcare professionals in combination (low-quality evidence), although it is uncertain if such a change is meaningful for patients. In terms of patient quality of life, we found no evidence that probiotics make a difference (low-quality evidence). We found no evidence of an increase in adverse events; those reported in included studies that were related to treatment were tummy and gut upset with diarrhoea, constipation, vomiting, and colic pains (low-quality evidence). Analysis suggests that further probiotic studies assessing the effects of eczema symptoms may not be worthwhile, as they are unlikely to change the outcome at the end of active treatment. The quality of evidence supporting our key findings was low, apart from one moderate rating for participant-rated symptoms of eczema. Reasons for this include variability between studies, which could not be explained, and not enough available data.