DISCUSSION
This NMA synthesizes evidence on the efficacy and safety of various postbiotic strains for treatment of pediatric AD. Only LR showed significant benefit compared to placebo. Evidence suggests LR may reduce AD symptoms, but CoE is low. LR had a statistically significant effect in reducing SCORAD values in the sensitivity analysis, but results did not reach clinical significance. The MD and upper limit of the 95% CI were less than the MCID. A reduction of least 8.7 points in SCORAD is considered clinically significant. 33
Effectiveness is a crucial factor in clinical decision-making, but other factors including safety and cost-effectiveness are also important.34 In this study, there was no significant difference in adverse events between LR and placebo, based on moderate certainty of evidence. Although LP2 was the highest-ranked postbiotic strain in terms of safety, it only ranked 6th (out of 7 postbiotic preparations) in the efficacy outcome and did not demonstrate significant benefit when compared to placebo.
MV2 and MV3 demonstrated significant harm, which may be explained by the route of administration since Mycobacterium vaccae was administered intradermally. The other postbiotic species were administered orally. Injection site reactions such as induration and erythema were common and dose-related.7-8
Only one study that tested a mixed preparation of postbiotics was included in the review. However, it was not included in the NMA due to inadequate data. Their study showed favorable effect on AD at 6 months of treatment, with no major safety concerns. This finding is similar to the NMA of Tan-Lim et al. 2020 that compared probiotic preparations for the treatment of pediatric AD, three of the six mixed probiotic preparations demonstrated significant reduction in AD symptoms. This effect was hypothesized to be due to the synergistic activity of the bacteria included in the mix.23
Furthermore, of the 17 probiotic preparations included in the NMA ofTan-Lim et al. 2020 , probiotic Mix 1 (ProbioMix1;Bifidobacterium animalis subsp. lactis CECT 8145,Bifidobacterium longum, CECT 7347, Lactobacillus casei CECT 9104 ) had the most favorable effect in reducing AD symptoms (SMD = -1.94 (95% CI of -2.65 to -1.94). None of the strains included in this Mix1 were included in this NMA on postbiotics. ProbioMix1 had MDSCORAD of -19.2 (95% CI of -24.76 to -13.64) compared to placebo, which was clinically significant. In this NMA on postbiotics, LR had the most favorable effect in reducing AD symptoms, but results were not clinically significant.
In the Tan-Lim et al. 2020 study, Lactobacillus rhamnosusMP 108 also showed significant benefit in reducing AD symptoms (SMD –0.62, 95% CI –1.12 to –0.13).23 Although the LR postbiotic evaluated in this NMA consists of a different strain (L. rhamnosus IDCC 3201), the L. rhamonsus species seem to have a promising effect on atopic dermatitis both in probiotic and postbiotic form.
There is one study that evaluated the effect of live and heat-inactivated Lactobacillus rhamnosus GG (LGG) compared to placebo,31 but this was not included in this NMA since participants had concomitant cows’ milk allergy. This trial showed significant benefit only with the viable LGG supplementation. The authors emphasized the importance of including the safety variable for future research on heat-inactivated LGG, as adverse gastrointestinal symptoms were observed.
One of the main limitations of this study is the limited number of studies supporting each pairwise comparison and the absence of direct evidence providing head-to-head comparisons of the postbiotic strains. Multiple treatment comparisons could not be performed for the interventions. The imprecise results found in most pairwise comparisons may be due to the limited available data. However, this is expected given the recentness of the postbiotic field. Consensus on the naming and defining the concept of ‘killed microorganism that benefits its host’ was only recently established.14A recent convention attended by foremost experts in the field was organized last December 2022 for further discussion35. Nevertheless, the study sheds light on postbiotic treatments’ potential benefits and safety concerns for AD management.