Objective To explore the causal correlation of gut microbiota and their metabolic pathways with short stature using a two-sample Mendelian randomization (MR) approach. Methods Genome-wide association study (GWAS) summary data on gut microbiota from the Dutch Microbiome Project (DMP) and FINRISK 2002 (FR02), as well as genetic data on height from the GIANT Consortium, were utilized. The inverse variance weighted (IVW) method, MR Egger regression, weighted median (WME), simple mode, and weighted mode were employed to investigate the causal relationship between gut microbiota, metabolic pathways, and short stature, with the IVW method serving as the primary approach. Sensitivity analysis, heterogeneity testing, pleiotropy testing, and outlier detection were conducted to validate the stability and reliability of the results. Results The IVW results indicated a causal relationship between five gut microbial taxa, three metabolic pathways, and short stature. Specifically, Bacillales (OR=1.24, 95%CI: 1.11 - 1.38, PFDR=0.007), GCA-900066755 (OR=1.06, 95%CI: 1.03 - 1.09, PFDR<0.001), "pyruvate fermentation to acetate and lactate II" (OR=1.04, 95%CI: 1.02 - 1.06, PFDR<0.001), and "urate biosynthesis/inosine 5'-phosphate degradation" (OR=1.05, 95%CI: 1.02 - 1.08, PFDR=0.042) were positively associated with height. Conversely, Clostridium E sporosphaeroides (OR=0.93, 95%CI: 0.89 - 0.97, PFDR=0.023), Escherichia flexneri (OR=0.88, 95%CI: 0.84 - 0.93, PFDR<0.001), GCA-900199385 sp900320755 (OR=0.96, 95%CI: 0.94 - 0.98, PFDR<0.001), and "heme B biosynthesis from glutamate" (OR=0.97, 95%CI: 0.96 - 0.98, PFDR<0.001) were negatively associated with height. No significant pleiotropy or heterogeneity was detected among the instrumental variables (IVs). Conclusions There is a clear causal relationship between gut microbiota, related metabolic pathways, and short stature. The specific biological mechanisms require further investigation, and the identified targets may provide valuable insights for future research.
Key words
gut microbiota /
short stature /
mendelian randomization
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