Results
A total of 1986 studies were screened, 355 of these were assessed for
eligibility and 330 were excluded (Figure S1). Reasons for exclusion
included non-original studies (221 were narrative
reviews/meta-analysis), studies in which outcomes were not relevant for
the present objectives, and studies reporting results that were not
suitable for inclusion in the present systematic review or
meta-analysis. After a full-text review of the 405 studies, 75 studies
were included (Figure S1).
Out of 75 included studies, 33 studies were related to the outer layer
biodiversity [23 used dust samples and 10 used environmental
biodiversity measures (e.g., species richness index, land-use gradient,
and plant diversity)] and 42 studies were related to the inner layer
biodiversity (2 studies characterized urine and skin microbiota
diversity, 16 studies collected stool samples, and 25 characterize
airway microbiota diversity) (Figure 1).
Characteristics of the 75 included studies are shown in Table S1 (and
online supplement pp 6-8). Furthermore, 39 of the 75 included studies
were classified as poor quality, 5 were classified as fair quality, and
31 were classified as good quality (Table S1). Study design limitations
were mainly due to unadjusted potential confounders and/or self-reported
outcome.
3.1.
Outer layer biodiversity
The summary results on the association between outer layer biodiversity
and asthma, wheezing, and allergic sensitization are shown in Table S2
(and online supplement p 7).
Studies included in
meta-analysis
Shannon diversity index
Figure 2 presents the forest plot for the association between
Shannon diversity index based on
dust sampling techniques and the risk of asthma. The summary effect
estimate indicated a protective effect, but it was not statistically
significant (OR (95% CI) = 0.77 (0.55; 1.06),
I2 = 72.4%, p =0.027) (Figure 2). The funnel
plot (Figure S3) suggested an asymmetric pattern, but the Egger’s test
for publication bias was not statistically significant (t=3.16,p =0.195).
Bacterial richness
The summary effect estimate (odds ratio) for the association between
bacterial richness and asthma [OR (95% CI) = 0.74 (0.57; 0.96)] was
consistent with the hypothesis that
exposure to higher biodiversity,
assessed as bacterial richness, has a protective effect on the
development of asthma (Figure 3). There was considerable heterogeneity
(I2=71.8%, p =0.003) across the studies (Figure
3). The funnel plot (Figure S4) was asymmetric, indicating some
publication bias (Egger’s test: t=5.15, p =0.007).
3.2. Inner layer
biodiversity
Table S2 summarises the evidence on the association between inner layer
biodiversity and asthma, wheezing, and allergic sensitization (online
supplement pp 7-8).
Studies included in
meta-analysis
Shannon diversity index
The mean/median of the Shannon diversity index among individuals with
and without asthma was reported in 7 studies. However, the study
conducted by Park et al. 16 was excluded based on
quality. The random effects model (n=6) provided a significantly
increased standardized mean difference [SMD (95% CI) = 0.31 (0.14;
0.48)], indicating that the bacterial diversity was slightly higher
among individuals with asthma (Figure 4). There was no significant
heterogeneity between study-specific estimates
(I2=0%, p =0.88) (Figure 4), but the
sensitivity analysis including the study conducted by Park et al.16 increased heterogeneity up to 60% (Figure S6).
Bacterial richness
The mean/median of the bacterial richness/abundance among individuals
with and without asthma was reported in 6 studies. The study conducted
by Park et al. 16 was excluded because of low quality.
The summary standardised mean difference (95% CI) from the random
effects model (n=5) was 0.25 (0.06; 0.44) (Figure 5), indicating that
bacterial richness/abundance was slightly higher among individuals with
asthma. Consistent with Shannon diversity index, there was no
significant heterogeneity between study-specific estimates
(I2=0%, p =0.70) (Figure 5), but when including
the study conducted by Park et al. 16 the
heterogeneity increased to 52% (Figure S10).
The funnel plots (Figure S14 and S15) show an apparently asymmetrical
pattern that may be indicative of publication bias. Despite this
apparent asymmetry, Egger’s tests for publication bias were not
statistically significant (t=-1.43, p =0.226 for studies on
Shannon diversity index, and t=-0.45, p =0.680 for studies on
bacterial richness), suggesting absence of publication bias.
The meta-analysis of 4 study-specific effect estimates, investigating
associations between bacterial richness and asthma, showed no
significant association between bacterial richness and asthma [OR
(95% CI) = 1.14 (0.83; 1.56)] (Figure 6). The forest plot shown in
Figure 6 demonstrates significant heterogeneity
(I2=62.0%, p =0.048) across the studies. The
funnel plot (Figure S16) suggested an asymmetric pattern; however, the
Egger’s test indicated no publication bias (t=-0.26, p =0.819).