<p>Standard protocols for meta-analysis of association studies are inadequate for microbiome data due to their complex compositional structure, leading to inaccurate and unstable microbial signature selection. To address this issue, we introduce Melody, a framework that generates, harmonizes, and combines study-specific summary association statistics to powerfully and robustly identify microbial signatures in meta-analysis. Comprehensive and realistic simulations demonstrate that Melody substantially outperforms existing approaches in prioritizing true signatures. In the meta-analyses of five studies on colorectal cancer and eight studies on the gut metabolome, we showcase the superior stability, reliability, and predictive performance of Melody-identified signatures.</p>