Objective To analyze the causal relationship between gut microbiota and childhood asthma based on Mendelian randomization (MR). Methods The human gut microbiota dataset was downloaded from the MiBioGen database, and 196 known bacterial groups (9 phyla, 16 classes, 20 orders, 32 families, and 119 genera) were retained as exposure factors. Single nucleotide polymorphisms (SNPs) that were strongly correlated with exposure factors and independent of each other were selected as effective instrumental variables. A childhood asthma dataset with 3 025 patients and 135 449 controls was downloaded from the genome-wide association studies database as the outcome variable. Two-sample MR analysis was performed using inverse variance weighted, weighted median, MR-Egger, weighted model and simple model methods, respectively. The causal association between gut microbiota and childhood asthma was evaluated by odds ratio (OR). Sensitivity analysis was performed by leave-one-out method. Horizontal pleiotropy was tested by MR-Egger intercept test and MR-PRESSO global test, and Cochran’s Q test was used for heterogeneity. Results A total of 15 out of 196 gut microbiota groups were found to have a causal association (P<0.05) with the risk of childhood asthma, with a total of 181 SNPs included in the analysis. Inverse variance weighted analysis showed that Mollicutes [OR=1.42, 95% confidence interval (CI) (1.10, 1.83), P=0.007], Escherichia-Shigella [OR=1.39, 95%CI (1.02, 1.90), P=0.036], Oxalobacter [OR=1.30, 95%CI (1.10, 1.54), P=0.002], Ruminococcaceae UCG-009 [OR=1.34, 95%CI (1.09, 1.64), P=0.006] and Tenericutes [OR=1.42, 95%CI (1.10, 1.83), P=0.007] were significantly positively correlated with childhood asthma. Actinobacteria [OR=0.76, 95%CI (0.58, 0.99), P=0.042], Bifidobacteriaceae [OR=0.76, 95%CI (0.58, 0.98), P=0.035], Eubacterium nodatum group [OR=0.81, 95%CI (0.70, 0.94), P=0.007], Bifidobacterales [OR=0.76, 95%CI (0.58, 0.98), P=0.035] and Actinobacteria [OR=0.74, 95%CI (0.56, 0.99), P=0.040] were negatively correlated with childhood asthma. In addition, the results of leave-one-out sensitivity analysis were stable, MR-Egger intercept test and MR-PRESSO global test showed no horizontal pleiotropy, and Cochran’s Q test showed no heterogeneity. Conclusions There is a causal relationship between gut microbiota and childhood asthma. Mollicutes, Escherichia-Shigella, Oxalobacter, Ruminococcaceae UCG-009 and Tenericutes may increase the risk of childhood asthma. Actinobacteria, Bifidobacteriaceae, Eubacterium nodatum group, Bifidobacterales and Actinobacteria can reduce the risk of childhood asthma.
Objective To analyze the causal relationship between gut microbiota and tic disorder based on Mendelian randomization (MR). Methods A total of 196 known microbiota (9 phyla, 16 classes, 20 orders, 32 families, and 119 genera) in the human intestinal microbiota dataset downloaded from the MiBioGen database were selected as the exposure factors, and the dataset of tic disorder (finn-b-KRA_PSY_TIC) containing 172 patients and 218620 controls was downloaded from the genome-wide association study database as the outcome variable. Inverse variance weighted was used as the main analysis method, and the causal relationship between gut microbiota and tic disorder was evaluated using odds ratio (OR) and its 95% confidence interval (CI). Horizontal pleiotropy was tested by MR-Egger intercept and MR-PRESSO global test, heterogeneity was assessed by Cochran’s Q test, and sensitivity analysis was performed by leave-one-out method. Results Inverse variance weighted results showed that the Family Rhodospirillaceae [OR=0.398, 95%CI (0.191, 0.831), P=0.014], Order Rhodospirillales [OR=0.349, 95%CI (0.164, 0.743), P=0.006], and Parasutterella [OR=0.392, 95%CI (0.171, 0.898), P=0.027] had negative causal relationships with tic disorder. The Genus Lachnospira [OR=8.784, 95%CI (1.160, 66.496), P=0.035] and Candidatus Soleaferrea [OR=2.572, 95%CI (1.161, 5.695), P=0.020] had positive causal relationships with tic disorder. In addition, MR-Egger intercept and MR-PRESSO global test showed no horizontal pleiotropy, Cochran’s Q test showed no heterogeneity, and leave-one-out sensitivity analysis showed the results were stable. Conclusions A causal relationship exists between gut microbiota and tic disorder. The Family Rhodospirillaceae, Order Rhodospirillales, and Parasutterella are associated with a decreased risk of tic disorder, while the Genus Lachnospira and Candidatus Soleaverea can increase the risk of tic disorder.