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.