Objective To explore causal relationships between the gut microbiome and chronic respiratory diseases (asthma and chronic obstructive pulmonary disease (COPD)) and to dissect the underlying biological mechanisms. Methods Cross-sectional observational study: using data from 3 662 participants in the U.S. National Health and Nutrition Examination Survey (NHANES 2007–2012), dietary information was collected as a proxy for gut-microbiome features and linked to lung-function parameters and respiratory symptoms. Two-sample Mendelian randomization (MR): leveraging summary statistics from the Dutch Microbiome Project and Canada serum-metabolite genome-wide association studies (GWAS), we tested the causal effects of 412 gut-microbiome traits (207 taxa and 205 functional pathways) on asthma, COPD, and lung-function indices (FEV1, FVC, FEV1/FVC). Mediation MR was further performed to quantify the mediating roles of 1 091 serum metabolites. Functional validation: single-nucleotide polymorphism (SNP)-based gene mapping was used to prioritize candidate genes, which were then interrogated in COPD and asthma transcriptomic datasets (GSE38974 and GSE69683). Results Observational findings: higher probiotic intake was associated with increased asthma risk (OR=1.76, 95%CI 1.01 to 3.05, P=0.036) but reduced emphysema risk (OR=6.144×10?7, 95%CI 3.059×10?7 to 6.144×10?7, P<0.001). Dietary fiber intake correlated with lower cough prevalence (OR=0.97, 95%CI 0.96 to 0.99, P=0.006) and improved lung function. MR results: 23 microbial taxa and 21 metabolic pathways showed significant causal effects on asthma or COPD. For instance, adolescentis-group Bifidobacterium and Oxalobacter exacerbated asthma, whereas the phospholipid biosynthesis I pathway conferred protection. Lachnospiraceae bacterium 7_1_58FAA and Parasutterella excrementihominis increased COPD risk, while the reductive incomplete TCA cycle and aspartate pathway were protective. Among serum metabolites, 87 and 97 metabolites-including taurochenodeoxycholate-3-sulfate (protective against asthma) and sphingomyelin (protective against COPD)-significantly mediated the causal influences of the gut microbiome. Bioinformatic analyses: gut-microbiome-linked genes (e.g., FXYD1, SCN3B) were differentially expressed in COPD and asthma and were enriched in ion-channel transport, muscle contraction, and blood-circulation processes. Conclusion By integrating observational data, MR, and transcriptomics, this study provides the first multi-omics evidence that specific gut microbes and their metabolic pathways exert causal effects on asthma and COPD through serum metabolite mediation. These effects likely operate via modulation of ion homeostasis, muscle contraction, and blood circulation, offering novel avenues for early diagnosis and targeted intervention in chronic respiratory diseases.