Identification of core gut microbiomes
33 candidate gut microbiomes associated with the onset of childhood asthma were extracted from literature (Table 2). There are 20 overlapping microbiomes, namely core gut microbiomes, including Lactobacillus, Faecalibacterium, Akkermansia, Lachnospira, Veillonella, Roseburia, Blautia, Parabacteroides, Clostridiales, Clostridiaceae1, Firmicutes, Streptococcus, Oscillospira, Lachnospiraceae, Alistipes, Flavonifractor, Rikenellaceae, Dialister, Collinsella and Dorea between candidate microbiomes and Mibiogen (Fig. 3). Previous researches show that there is a positive correlation between Firmicutes and pediatric asthma, and there is also a negative correlation between Lactobacillus, Akkermansia, Ruminococcus 1, Ruminococcus 2, Clostridiales, Clostridiaceae 1, Alistipes, Rikenellaceae, Dialister, Collinsella, Dorea and childhood asthma. However, various studies in the literature exploring the relationship between Bifidobacterium, Faecalibacterium, Veillonella, Roseburia, Lachnospiraceae, Flavonifractor and childhood asthma have yielded different results.
Table 2
Core Gut Microbiomes Associated with Childhood Asthma
Gut microbiome | Correlation | Contributor |
Bifidobacterium | | |
| Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11] |
Positive | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[7; 8], Jakob Stokholm[14] |
Lactobacillus | Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11] |
Faecalibacterium | | |
| Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11], Jakob Stokholm[14] |
Positive | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[8], Rozlyn C T Boutin[10], David M Patrick[12] |
Akkermansia | Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11] |
Malassezia | Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11] |
Candida | Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11] |
Rhodotorula | Negative | Cristina Garcia-Maurino Alcazar[6], Kei E Fujimura[11] |
Lachnospira | | |
| Positive | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[8], Rozlyn C T Boutin[10] |
Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[8], Leah T Stiemsma[13] |
Rothia | Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[8], Leah T Stiemsma[13] |
Veillonella | | |
| Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[8], Jakob Stokholm[14] |
Positive | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[7], Marie-Claire Arrieta[8], Leah T Stiemsma[13] |
Peptostreptococcus | Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[8] |
Coprococcus | Negative | Cristina Garcia-Maurino Alcazar[6], Rozlyn C T Boutin[10] |
Roseburia | | |
| Negative | Cristina Garcia-Maurino Alcazar[6], Jakob Stokholm[14], Rozlyn C T Boutin[10], David M Patrick[12], Leah T Stiemsma[13] |
Positive | Jakob Stokholm[14] |
Blautia | Negative | Cristina Garcia-Maurino Alcazar[6], Rozlyn C T Boutin[10] |
Parabacteroides | Positive | Cristina Garcia-Maurino Alcazar[6], Rozlyn C T Boutin[10] |
Ruminococcus 1 | Negative | Cristina Garcia-Maurino Alcazar[6], Jakob Stokholm[14], Rozlyn C T Boutin[10], David M Patrick[12] |
Ruminococcus 2 | Negative | Cristina Garcia-Maurino Alcazar[6], Jakob Stokholm[14], Rozlyn C T Boutin[10], David M Patrick[12] |
Clostridiales | Negative | Cristina Garcia-Maurino Alcazar[6], Leah T Stiemsma[13] |
Clostridium neonatale | Negative | Cristina Garcia-Maurino Alcazar[6], Leah T Stiemsma[13] |
Clostridiaceae 1 | Negative | Cristina Garcia-Maurino Alcazar[6], Leah T Stiemsma[13] |
Firmicutes | Positive | Cristina Garcia-Maurino Alcazar[6], Leah T Stiemsma[13] |
Streptococcus | Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[7] |
Pichia kudriavzevii | Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[7] |
Oscillospira | Negative | Cristina Garcia-Maurino Alcazar[6], Marie-Claire Arrieta[7] |
Lachnospiraceae | | |
| Negative | Cristina Garcia-Maurino Alcazar[6], Leah T Stiemsma[13] |
Positive | Jakob Stokholm[14] |
Alistipes | Negative | Cristina Garcia-Maurino Alcazar[6], Jakob Stokholm[14], Leah T Stiemsma[13] |
Flavonifractor | | |
| Positive | Cristina Garcia-Maurino Alcazar[6], Leah T Stiemsma[13] |
Negative | Jakob Stokholm[14] |
Faecalibacterium prausnitzii | Positive | Cristina Garcia-Maurino Alcazar[6], David M Patrick[12] |
Ruminococcus bromii | Negative | Cristina Garcia-Maurino Alcazar[6], David M Patrick[12] |
Rikenellaceae | Negative | Cristina Garcia-Maurino Alcazar[6], David M Patrick[12] |
Dialister | Negative | Cristina Garcia-Maurino Alcazar[6], Jakob Stokholm[14], David M Patrick[12] |
Gemmiger | Negative | Michiel A. G. E. Bannier[9] |
Escherichia | Negative | Michiel A. G. E. Bannier[9] |
Collinsella | Negative | Michiel A. G. E. Bannier[9] |
Dorea | Negative | Michiel A. G. E. Bannier[9] |
Effect of gut microbiomes on childhood asthma risk in East Asians
Regrettably, we did not detect significant causal associations between core gut microbiomes and the risk of childhood asthma (Fig. 4A, B). However, among non-core gut microbiomes, the result of IVW displayed the possible causal effects of order Actinomycetales (OR = 0.390, 95% CI :0.173–0.882, P = 0.024) (Fig. 4E), family Actinomycetaceae (OR = 0.391, 95% CI :0.173–0.883, P = 0.224) (Fig. 4F), genus Actinomyces (OR = 0.528, 95% CI :0.289–0.965, P = 0.038) and genus Fusicatenibacter (OR = 0.465, 95% CI :0.230–0.938, P = 0.019) (Fig. 4G) on decreased childhood asthma risk (Fig. 4B). Although results of supplementary models including MR-Egger, Weighted median, Simple mode and Weighted mode, were not statistically significant, the direction of effect remained consistent with IVW models (OR < 1). On the contrary, the genus Coprobacter had a significant positive correlation with the risk of childhood asthma (OR = 1.826, 95% CI :1.106–3.016, P = 0.032) (Fig. 4G). The results of other models were not significant, but they consistently indicated a positive association between the genus Coprobacter and childhood asthma (OR > 1). The aforementioned results were unaffected by heterogeneity or horizontal pleiotropy. No additional significant causal associations between other gut microbiomes and the risk of childhood asthma were found (Fig. 4C-G). All results of tests for heterogeneity and horizontal pleiotropy are reported in the Supplementary Table 2.
Effect of gut microbiomes on childhood asthma risk in European population
Unlike previous studies[6; 12; 14], the results of the IVW analysis showed that the genus Dialister significantly increased the risk of childhood asthma (OR = 1.251, 95% CI :1.016–1.539, P = 0.035). According to the results of weighted median model, the genus Dialister exhibited significant positive causal association with childhood asthma risk (OR = 1.325, 95% CI :1.004–1.749, P = 0.046), aligning with the findings of the IVW analysis. The results of simple mode (OR = 1.396, 95% CI :0.882–2.229, P = 0.185), and weighted mode models (OR = 1.402, 95% CI :0.857–2.293, P = 0.209) were not significant, but they still indicated a positive association between the genus Dialister and childhood asthma (OR > 1). We did not detect that other core gut microbiomes were significantly causally associated with the childhood asthma risk (Fig. 5A). At the genus biological level of non-core gut microbiota, based on the MR analysis results between non-core gut microbiomes and pediatric asthma, the IVW models indicated that genus Eubacterium nodatum group (OR = 1.12, 95% CI:1.002–1.251, P = 0.047) and genus Bilophila (OR = 1.29, 95% CI:1.046–1.581, P = 0.017) had a significant positive correlation with childhood asthma. On the other hand, there was a negative correlation between genus Holdemanella (OR = 0.82, 95% CI:0.706–0.951, P = 0.009), genus Oxalobacter (OR = 0.84, 95% CI:0.747–0.955, P =0.007) and genus Slackia (OR = 0.81, 95% CI:0.655–0.996, P = 0.046) and childhood asthma. The MR estimates from supplementary models consistently supported their negative effect on childhood asthma (Fig. 5B). The aforementioned results were unaffected by heterogeneity or horizontal pleiotropy. No further significant causal associations between the remaining non-core gut microbiota and the risk of childhood asthma could be identified (Fig. 5C-G). All results of tests for heterogeneity and horizontal pleiotropy are reported in the Supplementary Table 3.
Effect of gut microbiomes antibiotic resistome on childhood asthma risk
To further delve into the effect of gut microbiome resistome on childhood asthma, MR analyses were conducted in East Asians. The results of the IVW analysis showed that the Pielou's index Evenness, one of the diversity indices, exhibited significant causal associations with the reduced risk of childhood asthma (OR = 0.825, 95% CI:0.684–0.994, P = 0.043). The results of the weighted median (OR = 0.866, 95% CI :0.670–1.120, P = 0.274), simple mode (OR = 0.892, 95% CI :0.608–1.307, P = 0.571), and weighted mode models (OR = 0.889, 95% CI :0.603–1.309, P = 0.564) were not statistically significant. However, their effect directions were consistent with the IVW results (OR < 1). This result was unaffected by heterogeneity or horizontal pleiotropy. Ultimately, we did not detect that the other diversity indices (including Richness and Shannon) and 4 ARGs (including MLS_ermX, Multidrug_emrE, Quinolone_norB and Vancomycin_vanX) were significantly causally associated with the childhood asthma risk (Fig. 6). All results of tests for heterogeneity and horizontal pleiotropy are reported in the Supplementary Table 4.