Gut Microbiome and Childhood Asthma: a Mendelian Randomization Study
Authors: zheng zhiwei , Zhou Yongmao , Chen Pan , Huang Qinhai , Li Baofei , Huang Ganghua 
Published: January 2024

A few gut microbiomes have been reported in observational studies to be associated with childhood asthma. Antibiotic resistome of gut microbiomes may also influence childhood asthma risk. However, the underlying causal effect remains undefined. We attempted to explore the causal association of these conditions through Mendelian randomization (MR) analysis. First, we review literatures to identify core gut microbiomes potentially associated with childhood asthma. The instrumental variables (IVs) for gut microbiome and gut microbiomes antibiotic resistome were obtained from MiBioGen consortium and a multiomics study respectively. And the genetic instruments for childhood asthma in East Asian populations and European were selected from genome-wide association studies (GWAS). We implemented Two-sample MR analysis to elucidate the effect of gut microbiome and gut microbiome antibiotic resistome on childhood asthma risk. The inverse variance weighted (IVW) was employed as the primary analysis, followed by heterogeneity and pleiotropy analysis. In the European population, within the core gut microbiomes, genus Dialister was significantly positively associated with childhood asthma risk by IVW (OR = 1.251, 95% CI :1.016–1.539, P = 0.035). Moreover, there was a positive correlation between genus Eubacterium nodatum group (OR = 1.12, 95% CI:1.002–1.251, P = 0.047), genus Bilophila (OR = 1.29, 95% CI:1.046–1.581, P = 0.017) and childhood asthma risk. Conversely, 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) exhibited a significant negative correlation with childhood asthma risk. In the East Asian population, our analysis revealed correlations between decreased childhood asthma risk and the order Actinomycetales (OR = 0.390, 95% CI :0.173–0.882, P = 0.024), family Actinomycetaceae (OR = 0.391, 95% CI :0.173–0.883, P = 0.224), 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). Conversely, genus Coprobacter showed a significant positive correlation with childhood asthma risk (OR = 1.826, 95% CI :1.106–3.016, P = 0.032). Finally, there was a negative correlation between Evenness, an index representing the α-diversity of the gut antibiotic resistome, and childhood asthma risk (OR = 0.825, 95% CI:0.684–0.994, P = 0.043).
Conclusions: This study is the first to employ MR analysis to validate the association between gut microbiomes identified in literature and childhood asthma risk. We try to explore additional bacterial taxes that may be associated with childhood asthma risk. Furthermore, the present study innovatively explores the effect of the gut microbiome antibiotic resistome on the risk of pediatric asthma using MR analysis. These findings provide opportunities for early intervention on childhood asthma and offer new insights into the underlying mechanisms of childhood asthma. However, further studies are required to validate and generalize the results in future research.